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25 January 2024, Volume 40 Issue 2
Symposiums
Application and prospects of ctDNA detection in HPV associated cervical cancer
Baoni JIANG,Meiqin ZHANG,Lu YANG,Zhiyuan CHEN,Na′na HAN
2024, 40(2):  129-132.  doi:10.3969/j.issn.1006-5725.2024.02.001
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Circulating tumor DNA (ctDNA) is a kind of cell-free DNA derived from tumors, which carries comprehensive tumor genetic information; Recent studies have found that ctDNA detection can play a role in the early diagnosis, targeted therapy, and prediction of recurrence in tumors. Human papillomavirus (HPV)-associated gynecological malignancies include most cervical cancer, some vulvar cancer, and vaginal cancer. High-risk HPV long-term infection and integration with cell genome are important causes of these cancers. Studies found that the use of ctDNA detection technology to dynamically monitor changes in HPV-ctDNA can provide valuable information for the clinical management and prognosis of these cancers. Thus, HPV-ctDNA is expected to become an biomarker for HPV- associated tumors.

Feature Reports:carcinoma of cervix
Generation of MCM2 gene inducible knockout cervical cancer HeLa cells and its effect on DNA replication
Ping LI,Tuo TANG,Aixue ZHENG,Luping ZHANG,Tao WANG,Xian HONG,Zhihui DENG
2024, 40(2):  133-139.  doi:10.3969/j.issn.1006-5725.2024.02.002
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Objective To generate minichromosome maintenance protein 2 (MCM2) gene knockout cervical cancer HeLa cell lines using inducible CRISPR/Cas9 technology, and to explore the effect of MCM2 on DNA replication and replication stress. Methods The inducible CRISPR/Cas9 system, TLCV2, was used to construct MCM2 knockout HeLa cell lines. And the cell lines were divided into control group (Control), knockout group 1 (KO1), and knockout group 2 (KO2). Western blot, Edu incorporation experiment, real-time quantitative PCR (qPCR), immunofluorescence and MTT assay were used to analyze the effects of MCM2 knockout on DNA replication and replication stress induced by hydroxyurea. Results The CRISPR/Cas9 system successfully knocked out the MCM2 gene after induction, and MCM2 knockout affected the stability of MCM2-7 complex. Compared with the control cells, MCM2 knockout cells had a dramatic decrease in the capacity of DNA replication, and the mRNA levels of Cyclin A1, Cyclin E1 and CDK4. Under DNA replication stress, MCM2 knockout cells decreased cell viability, DNA damage repair capacity, and increased genomic instability compared with control cells. Conclusion Knockout of MCM2 gene reduces the DNA replication capacity of HeLa cells under normal conditions and cell viability under replication stress. This study successfully generates MCM2 gene inducible knockout HeLa cell lines, laying the foundation for further research on the role and biological function of MCM2 gene in the occurrence and progression of cervical cancer.

Efficacy of the ACS NSQIP surgical risk calculator in open radical hysterectomy
Shenglong YUAN,Huanhuan HU,Zhen GONG
2024, 40(2):  140-145.  doi:10.3969/j.issn.1006-5725.2024.02.003
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Objectives To evaluate the complications predicting efficacy of the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) surgical risk calculator for cervical cancer patients undergoing open radical hysterectomy in China. Methods This study enrolled the cervical cancer patients (139 cases) undertaken open radical hysterectomy at Women's Hospital of Nanjing Medical University from January to December in 2021. Preoperative risk factors were abstracted from medical records and the surgical risk scores were calculated using ACS NSQIP surgical risk calculator. The association between risk scores and actual outcomes were assessed using logistic regression together with the c-statistic (area under ROC) and Brier score. Results The ACSNSQIP calculator did not predict accurately for serious complications, any complications, venous thromboembolism (VTE), readmission, return operation room and surgical site infection (SSI) compared with actual outcomes. There was significantly difference in the predicted and actual length of stay (3.93 ± 0.42 days vs. 13.11 ± 4.71 days, P < 0.001). Conclusions The ACS NSQIP surgical risk calculator failed to predict the postoperative complications and the length of hospital stay for cervical cancer patients undergoing open radical hysterectomy.

HPV16 E6 regulates miR-23a expression and promotes invasion and migration of cervical cancer cells
Min WANG,Dan MU,Dejun KONG,Li YANG,Lu YE,Dan HE
2024, 40(2):  146-152.  doi:10.3969/j.issn.1006-5725.2024.02.004
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Objective To investigate the effects of high-risk human papillomavirus 16 E6 protein (HPV16 E6 protein) on invasion and migration of cervical cancer SiHa cells via regulating the expression of expression miR-23a. Methods Tissue samples from 100 patients with cervical cancer HPV-negative, 100 HPV-positive patients, and 100 paracancerous normal tissues were collected; cervical cancer SiHa cells were divided into blank group, E6 overexpression group, negative transfection group, and E6 + miR-23a mimics group. The expression of miR-23a and HPV16 E6 mRNA were detected by qRT-PCR; MTT assay was used to detect the cell proliferation inhibition rate; flow cytometry to detect the apoptosis; Transwell chamber assay to detect cell invasion, and scratch test to detect the ability of cell migration. The expression of HPV16 E6, apoptosis related proteins (Caspase-3, Bax, Bcl-2), and migration related proteins (MMP-2, MMP-9) was detected by WB. Results The expression level of miR-23a was decreased in cervical cancer tissues, and that was lower in HPV positive cervical cancer tissues. Overexpression of E6 decreased the expression level of miR-23a, cell proliferation inhibition rate, apoptosis rate, Caspase-3 and Bax protein expression, and increased the expression of Bcl-2 protein, scratch healing rate, invasion cell number, MMP-2, MMP-9 protein expression (P < 0.05); miR-23a mimics reversed the effects of E6 overexpression on the above indicators. Conclusion HPV16 E6 promotes the invasion and migration of cervical cancer cells, which may be related to the regulation of miR-23a expression.

Feasibility of automatic segmentation of CTV and OARs in postoperative radiotherapy for cervical cancer using AccuLearning
Fei CHEN,Xiaoqin GONG,Yunpeng YU,Tao YOU,Xu WANG,Chunhua DAI,Jing HU
2024, 40(2):  153-157.  doi:10.3969/j.issn.1006-5725.2024.02.005
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Objective To explore the feasibility of automatic segmentation of clinical target volume (CTV) and organs at risk (OARs) for cervical cancer using AccuLearning (AL) based on geometric and dosimetric indices. Methods Seventy-five CT localization images with manual contouring data of postoperative cervical cancer were enrolled in this study. Sixty cases were randomly selected to trained to generate automatic segmentation model by AL, and the CTV and OARs of the remaining 15 cases were automatically contoured. Radiotherapy plans on the automatic segmentation contours were imported on the CT images of manual contours. The efficiency, Dice similarity coefficient (DSC), Hausdorff distance (HD) and dosimetric parameters were compared between the two methods. Results The time of automatic segmentation was significantly shorter than that of the manual contour(P < 0.05). The DSC of all structures were ≥ 0.87. The HD of bowel bag and rectum were about 10 mm, and that of the rest of OARs were less than 5 mm. CTV (D98, V90%, V95%, Dmean, HI), bowel bag (V50) and bladder (V50) had significant differences in dosimetric comparison(P < 0.05). Conclusion The automatic segmentation model based on AL can improve the efficiency of radiotherapy. Automatic segmentation of OARs has the potential of clinical application, while that of CTV still needs to be further modified.

Levels and clinical significance of serum miR-651 and miR-630 in patients with cervical cancer
Yongzhen ZHANG,Shanshan WANG,Hailing ZHAO,Liwei. XU
2024, 40(2):  158-162.  doi:10.3969/j.issn.1006-5725.2024.02.006
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Objective To investigate the levels and clinical significance of serum microRNA (miR)-651 and miR-630 in patients with cervical cancer. Methods From June 2017 to May 2020, 108 cervical cancer patients accepted by our hospital were collected as the cervical cancer group. Meantime, 100 cervical intraepithelial neoplasia (CIN) patients treated in our hospital were regarded as the CIN group, and 110 healthy individuals who underwent physical examination were regarded as the control group. Real-time fluorescence quantitative PCR (qRT-PCR) was applied to detect serum levels of miR-651 and miR-630, while analyzing the relationship between serum miR-651 and miR-630 as well as clinical features and prognosis of patients. Results The serum levels of miR-651 and miR-630 in the cervical cancer group and CIN group were obviously lower than those in the control group (P<0.05), while the serum levels of miR-651 and miR-630 in the cervical cancer group were obviously lower than those in the CIN group (P < 0.05). The expression levels of serum miR-651 and miR-630 were positively correlated (r = 0.542, P < 0.05). The serum levels of miR-651 and miR-630 were related to HPV infection, differentiation, lymph node metastasis, and FIGO staging (P < 0.05). The overall survival rate of patients with low levels of miR-651 and miR-630 was lower than that of patients with high levels. Cox regression analysis showed that, HPV infection, degree of differentiation, lymph node metastasis, FIGO staging, miR-651, and miR-630 were all influencing factors for the prognosis of cervical cancer patients (P < 0.05). Conclusion The serum levels of miR-651 and miR-630 in cervical cancer patients decrease, which are related to HPV infection, differentiation, lymph node metastasis, FIGO staging, and prognosis.

A clinicopathological analysis of cervical carcinoma with basaloid features
Yanrui ZHANG,Xinyi HUANG,Jian SHI,Yihui YANG,Limin LIU,Haiyan HU
2024, 40(2):  163-168.  doi:10.3969/j.issn.1006-5725.2024.02.007
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Objective To investigate the clinical and pathological features of adenoid basal cell carcinoma (ABC), adenoid cystic carcinoma (ACC), and basaloid squamous cell carcinoma (BSCC) with basaloid characteristics and improve the diagnostic and differential diagnostic ability of clinicians and pathologists for these lesions. Methods A retrospective study was conducted on the clinical and pathological data of 4 cases of ABC, 1 case of ACC, and 3 cases of BSCC diagnosed and treated at Shenzhen Maternal and Child Health Hospital, Southern Medical University from April 2018 to December 2022. Pathological slides were reviewed and relevant literature was analyzed and summarized. Results All three types of tumors were common in postmenopausal women and were associated with high-risk HPV infection. ABC was a low-grade cancer and patients were often clinically asymptomatic. It was usually detected incidentally during cervical screening due to cytological abnormalities, or after cervical cone biopsy or hysterectomy for HSIL. It presented as superficial cervical infiltration and clinical staging was often early. ACC and BSCC were intermediate to high-grade cancers and they often presented with postmenopausal vaginal bleeding. A visible mass was observed on the cervix. The clinical staging was intermediate to advanced. The three types of lesions could coexist. Careful observation of the morphological characteristics and immunohistochemical staining could help with differential diagnosis. None of the 8 patients experienced recurrence or metastasis during follow-up. Conclusion Cervical ABC, ACC and BSCC are rare and they originate from reserve cells. They share the similarities in clinical and pathological morphology, but differ in treatment and prognosis. So, accurate differentiation among them has important clinical significance.

The expression of WDR5 in cervical cancer tissue and its relationship with clinical and pathological characteristics of patients
Pixi WEI,Yu DENG,Cailing ZHAO,Liu XU,Min ZHANG
2024, 40(2):  169-173.  doi:10.3969/j.issn.1006-5725.2024.02.008
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Objective To investigate the expression of WD repeat-containing protein 5 (WDR5) in cervical cancer tissue and its relationship with clinical pathological characteristics and prognosis of patients. Methods 105 CA patients admitted to our hospital from January 2018 to March 2020 were included as the study subjects, the cancer tissue and adjacent tissue samples of patients were collected, Immunohistochemical staining and Western blot were used to detect the level of WDR5 in CA tissue and adjacent cancer tissues. Immunohistochemistry and Western blot were used to determine the level; Survival analysis was conducted using the Kaplan Meier method; The influencing factors of patient prognosis were analyzed through Cox regression. Results Among 105 CA tissue samples, the positive expression rate of WDR5 (WDR5 positive cases/total cancer tissue cases) was 68.57% (72/105), which was higher than 22.86% (24/105) in adjacent cancer tissues (P < 0.05); Compared to adjacent tissues (1.00 ± 0.11), the expression level of WDR5 was higher in CA tissues (4.66 ± 0.98) (t = 38.030, P < 0.05). The expression level of WDR5 is related to the degree of differentiation, TNM staging, and lymph node metastasis (P < 0.05); The survival rate of WDR5 positive expression was 65.28% (47/72) lower than that of negative expression of 90.91% (30/33) (Log rank χ2 = 6.732, P = 0.009); TNM staging, WDR5, degree of differentiation, and lymph node metastasis are all influencing factors for patient prognosis (P < 0.05). Conclusion The expression of WDR5 is elevated in cervical cancer tissues, and its changes are closely related to TNM staging, differentiation, lymph node metastasis, and prognosis in cervical cancer patients.

Basic Research
Mechanism of iron death induced by high homocysteine via TRPC6/NF⁃κb in glomerular podiatocytes
Xiaoqin LI,Lexin WANG,Xiaojun MA,Na LI,Guanjun LU,Zhihan ZHANG,Pengcheng. ZHANG
2024, 40(2):  174-181.  doi:10.3969/j.issn.1006-5725.2024.02.009
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Objective To investigate the mechanism of iron death induced by TRPC6/NF?κB in glomerular podiocytes mediated by high homocysteine (Hcy). Methods Mouse glomerulopocytes were cultured in vitro and divided into Control group (0 μmol/L Hcy) and Hcy group (80 μmol/L Hcy). After 48h of intervention, Western blot was used to detect the expression levels of iron death related proteins GPX4 and SLC7A11 and TRPC6 and NF?κB. Real-time quantitative fluorescence PCR(qRT-PCR) and immunofluorescence were used to detect the expression of TRPC6. The level of podocyte apoptosis was detected by flow cytometry. Malondialdehyde (MDA) assay kit was used to determine intracellular MDA levels. After transfection of TRPC6 interference fragment and TRPC6 negative control (NC), qRT-PCR was divided into Control, si-NC and si-TRPC6 (Si-TRPC6-1, Si-TRPC6-2, Si-TRPC6-3). Western Blot was divided into Control, Hcy, si-NC+Hcy, si-TRPC6+Hcy.The expression of TRPC6 mRNA was detected by qRT-PCR. The expression levels of GPX4, SLC7A11, NF?κB and TRPC6 were detected by Western Blot. The level of podocyte apoptosis after interference was detected by flow cytometry. Results (1)Compared with Control group, the expression levels of iron death related proteins GPX4 and SLC7A11 in Hcy group were decreased, and the apoptosis rate was increased(P < 0.05). (2) Compared with Control group, TRPC6 protein, mRNA levels and immunofluorescence expression were increased in Hcy group.The level of MDA and the expression of NF?κB signaling pathway protein increased in Hcy group, and the comparison between the two groups had statistical significance (P < 0.05). (3) Compared with the si-NC group, the mRNA expression level of TRPC6 in si-TRPC6 (Si-TRPC6-1, Si-TRPC6-2, Si-TRPC6-3) group was decreased, and the interference effect of Si-TRPC6-3 was the best(P < 0.05). After transfecting TRPC6 NC and TRPC6 interference fragment and administering Hcy, there was no difference in GPX4, SLC7A11, NF?κB and TRPC6 expression in si-NC+Hcy group compared with Hcy group. Compared with the si-NC+Hcy group, the si-TRPC6+Hcy group had higher expression of iron death related proteins, GPX4 and SLC7A11, lower expression of NF?κB and TRPC6, and decreased apoptosis rate(P < 0.05). Conclusion This study confirmed that TRPC6/NF?κB can regulate iron death of renal podocytes under the induction of Hcy, which is one of the mechanisms leading to kidney injury.

LAMP3 inhibited the proliferation, metastatic and PC⁃3⁃induced vasculogenesis of HUVEC by regulating VEGF/AKT signaling
Canwei CHEN,Zhuangwen LIAO,Ziwen FAN,Shuai HUANG,Yan HUANG,Binwei CHEN
2024, 40(2):  182-187.  doi:10.3969/j.issn.1006-5725.2024.02.010
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Objective To explore the impactof Lysosome?Associated Membrane Protein 3 (LAMP3) on theproliferation, migration and angiogenesis of PC?3 cells. Methods LAMP3 expression in normal prostate epithelial cells and prostate cancer bone metastasis cells was detected using western blot and RT?PCR. Stable LAMP3?silenced PC?3 cells were constructed, and the effects of LAMP3 on proliferation, invasion, and migration of PC?3 cells were assessed using CCK8, scratch assay, and transwell assay, respectively. ELISA and angiogenesis assays were employed to examine the expression of VEGF and MMP9, as well as angiogenesis of HUVEC cells induced by PC?3 cells. Finally, WB and RT?PCR were used to detect the expression of VEGF, AKT/p?AKT. Results Our findings showed that the expression level of LAMP3 was significantly higherin prostate cellsthan in normal prostate epithelial cells, especially in PC?3 cells (P < 0.05). We also found that silencing LAMP3 could inhibit the proliferation, migration and invasion of PC?3 cells, along with the expression of VEGF and MMP9 and the PC?3 cells?induced angiogenesis, and these results were statistically significant (P < 0.05). Furthermore, LAMP3 downregulated the expression of VEGF and AKT/p?AKT in PC?3 cells. Conclusion LAMP3 can affect the proliferation, migrationand angiogenesis of PC?3 cells through the regulation of VEGF/AKT pathway. Thus, LAMP3 might be a potential therapeutic target for prostate cancer bone metastasis.

Based on the novel anti-heart failure drug ARNI, the mechanism of prevention of cardiotoxicity caused by anthracycline antitumor drugs was discussed
Jieqiong LIU,Yali YAO,Qian SUI,Ke LI,Fang HUANG,Yongqing. CAO
2024, 40(2):  188-194.  doi:10.3969/j.issn.1006-5725.2024.02.011
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Objective To explore the efficacy of a new anti?heart failure drug, Entresto, in the prevention of cardiotoxicity caused by doxorubicin (DOX). Methods Male adult ICR mice were randomly divided into three groups (n = 8): control group, DOX group and DOX plus Entresto group. Cardiac function of mice was measured by echocardiography. H9c2 cells were pretreated with Entresto (0 - 48 μmol/L) for 24 hours in the presence or absence of DOX (1 mmol/L), and then cell viability, oxidative stress, apoptosis and mitochondrial function were evaluated. Results As compared with the control group, leakage of CK, CK?MB and LDH increased significantly in the DOX group (P < 0.01), and left ventricular systolic dysfunction occurred. Entresto administration reversed these changes in the DOX group. The level of ROS and the number of apoptotic cells in cardiomyocytes in the DOX plus Entresto group were lower than those in the DOX group (P < 0.05). As compared with the DOX group, the level of ROS and the number of apoptotic cells in H9c2 cells decreased significantly in the Entresto plus DOX group (P < 0.05), and mitochondrial membrane potential increased significantly (P < 0.05). Entresto reversed the inhibitory effect of DOX on SIRT1/PGC?1α/MFN2 signaling pathway. Conclusions Entresto improves DOX?induced cardiotoxicity by inhibiting ROS?mediated oxidative stress and apoptosis, and its mechanism may be related to SIRT1/PGC?1α/MFN2 signal transduction pathway.

Hydroxynonenal alleviates neonatal sepsis⁃induced acute lung injury by inhibiting endothelial cell pyrosis
Zhouyou WU,Ting LI,Tengwei ZHANG,Qiaoyan FANG,Liu YANG,Qiao LI
2024, 40(2):  195-201.  doi:10.3969/j.issn.1006-5725.2024.02.012
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Objective To explore the role of 4-hydroxynonenal (HNE) in alleviating acute lung injury (ALI) induced by neonatal sepsis by inhibiting the focal death of endothelial cells (ECs). Methods Newborn mice were randomly divided into five groups: (1) Sham operation group (Sham group), (2) sham operation mice receiving HNE treatment group (Sham + HNE group), (3) cecal serosity (CS group), and (4)CS-treated GSDMD-/- mice group (CS + GSDMD-/- group). The degree of lung injury was evaluated by lung histopathology and lung wet/dry weight ratio. The ECs of mice were isolated and divided into the Ctrl group, LPS + ATP group, LPS + ATP + HNE-L group and LPS + ATP + HNE-H group. Western blot was used to evaluate the expression of HNE and caspase-1 pathway. Results Compared with CS group, the lung tissue scores of CS + HNE group and CS + GSDMD-/- group were significantly decreased (P < 0.05), and the ratio of wet to dry weight of lung tissues was significantly decreased (P < 0.05). Compared with the CS group, the 72-hour survival rates of mice in the CS + HNE group and CS + GSDMD-/- group were significantly improved (P < 0.05). The expressions of GSDMD-N, C-caspase-1, NLRP3, IL-18 and IL-1β in lung ECs of the CS + HNE group and CS + GSDMD-/- group were significantly lower than those of the CS group (P < 005). Compared with the Ctrl cells, LPS + ATP significantly decreased the cell viability (P < 0.05) and increased the protein expressions of GSDMD, C-caspase-1, NLRP3, IL-18 and IL-1β (P < 0.05), and these effects were also inhibited by HNE. Conclusion HNE can inhibit the focal death of lung ECs cells by inhibiting NLRP3/caspase-1 signal transduction, and improve ALI in septic mice.

Clinical Research
Effect of anterior quadratus lumborum block at the lateral supra⁃arcuate ligament on postoperative analgesia and inflammatory response in elderly patients undergoing robot⁃assisted radical prostatectomy
Guojiang YIN,Bixi LI,Pengxiao WEI,Yuqin YAN,Xiaoyang SONG,Kun LI
2024, 40(2):  202-206.  doi:10.3969/j.issn.1006-5725.2024.02.013
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Objective To investigate the effect of ultrasound?guided anterior quadratus lumborum block at lateral supra?arcuate ligament on postoperative analgesia and inflammation response in elderly patients undergoing robot?assisted laparoscopic radical prostatectomy. Methods A total of 60 elderly patients who had undergone robot?assisted laparoscopic radical prostatectomy from June 2022 to June 2023 were randomly divided into a group of ultrasound?guided anterior quadratus lumborum block at lateral supra?arcuate ligament combined with general anesthesia (observation group, n = 30) and a general anesthesia group (control group, n = 30). Both groups received patient?controlled intravenous analgesia after surgery. The first compression time of an analgesic pump and the numbers of effective compression and remedial analgesia were recorded. The VAS scores at postsurgical hours 2, 12, 24, and 48 during rest and coughing were recorded. Interleukin?6 (IL?6) and systemic immunoinflammatory index (SII) at one day before surgery and two hours, one day and three days after surgery were recorded. Anal exhaust time, length of postoperative hospital stay and occurrence of adverse reactions were recorded. Results The observation group, as compared with the control group, had significantly longer first compression time of an analgesic pump and had fewer numbers of effective compressions and remedial analgesic administrations (P < 0.05). The VAS scores during rest and coughing in the observation group were lower than those in the control group at postsurgical hours 2, 12, 24, and 48(P < 0.05). As compared with one day before surgery, both IL?6 and SII in the two groups increased at 2 hours, 1, and 3 days after surgery, but the changes in the observation group were lower than those in the control group (P < 0.05). As compared with the control group, the observation group had shorter anal exhaust time and length of postoperative hospital stay, and a lower incidence of adverse reactions (P < 0.05). Conclusions Ultrasound?guided anterior quadratus lumborum block at lateral supra?arcuate ligament can provide better postoperative analgesia, reduce inflammatory response and accelerate postoperative recovery in elderly patients undergoing robot?assisted laparoscopic radical prostatectomy.

Predictive value of bedside diaphragmatic ultrasound for pulmonary complications after thoracoscopic lobectomy
Gaofeng GUO,Xiaoguo RUAN,Yangyang WANG,Jiaqiang. ZHANG
2024, 40(2):  207-212.  doi:10.3969/j.issn.1006-5725.2024.02.014
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Objective To assess the predictive value of bedside diaphragmatic ultrasound in predicting pulmonary complications (PPCs) after thoracoscopic lobectomy. Methods The patients who had undergone elective thoracoscopic lobectomy in Henan Provincial People's Hospital were collected. General information and perioperative indicators were recorded. Diaphragmatic motility was detected by bedside ultrasound preoperatively and on postoperative days 1, 3, and 5. The patients were divided into two groups (PPCs group and non?PPCs group). Statistically different parameters in univariate analysis were included in multivariate logistic regression analysis to screen independent influencing factors of PPCs. Receiver operating curve (ROC) was drawn, and the performance of diaphragm ultrasound for predicting PPCs was evaluated by the area under the curve (AUC). Results 949 patients were included in this study. PPCs occurred in 537 patients (57.5%). Univariate analysis showed that as compared with the non?PPCs group, the proportion of diabetic patients and postoperative VAS score in the PPCs group increased, time to chest tube removal and one?lung ventilation, and postoperative hospital stay were longer. PPCs group had a lower DE value on the operative side and healthy side on postoperative days 1 and 3 and on the operative side alone on day 5 (P < 0.05). Multivariate logistic regression analysis showed that prolonged one?lung ventilation time, diabetes mellitus, DE values on the operative side and unoperative side on postoperative days 1 and 3, and decreased DE value on the operative side on day 5 were independent risk factors for PPCs. The ROC curve shows that the efficacy of DE for predicting PPCs on the operative and healthy sides on postoperative days 1 and 3 was relatively high (AUC of 0.797, 0.821, 0.933, and 0.929; respectively). The efficacy of DE for predicting PPCs on the operative side was poor on postoperative day 5 (AUC of 0.703 and 0.512, respectively). Conclusions A decrease in postoperative DE, prolonged one?lung ventilation time, and diabetes are independent risk factors for PPCs after thoracoscopic lobectomy. Bedside ultrasound evaluation of DE has a higher value in predicting PPCs three days after surgery.

Laser assisted sclerectomy and cataract extraction combined with angle separation in the treatment of angle closure glaucoma
Jiubing XIE,Xiyue CHEN,Xiangdong YUE,Yanhui CHEN,Wei JIANG,Shanshan YANG
2024, 40(2):  213-218.  doi:10.3969/j.issn.1006-5725.2024.02.015
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Objective To explore the clinical efficacy of laser?assisted sclerectomy and cataract extraction combined with angle separation in the treatment of angle?closure glaucoma. Methods A total of 162 patients with angle closure glaucoma were selected as the research subjects. Eighty?one patients in the experimental group underwent laser?assisted sclerectomy and cataract extraction combined with angle separation, and another 81 patients in the control group underwent cataract extraction combined with angle separation. The therapeutic effects of two groups of patients were observed. Results The postoperative visual acuity, BCVA, angle width, and corneal endothelial cell count of the experimental group were higher than those of the control group, but the intraocular pressure, central anterior chamber depth, and corneal thickness were all lower than those in the control group. The incidence of adverse reactions in the experimental group (6.2%) was lower than that in the control group (13.6%). During postoperative follow?up, there was no further increase in intraocular pressure in the two groups, while the height of filtering blebs in the control group decreased significantly when compared with that in the experimental group. One month after surgery, the BCVA and corneal endothelial cell count in the experimental group were higher than those in the control group (P<0.05), and the corneal thickness was lower than that in the control group (P<0.05), but no statistical significance was found at 3 and 6 months after surgery. The astigmatism in the experimental group was better than that in the control group 3 months after surgery, but there was no statistically significant difference at 1 month and 6 months after surgery. Conclusion Laser?assisted sclerectomy and cataract extraction combined with angle separation are effective and safe in the treatment of angle closure glaucoma.

Prognostic factors of patients undergoing percutaneous coronary intervention supported by extracorporeal membrane oxygenation
Qian ZHAO,Yan ZHANG,Qiao QIAO,Aiyun DENG
2024, 40(2):  219-224.  doi:10.3969/j.issn.1006-5725.2024.02.016
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Objective To explore the clinical value of transthoracic echocardiography (TTE) and related clinical indexesin the evaluation of percutaneous coronary intervention (PCI) supported by arteriovenous extracorporeal membrane oxygenation (VA-ECMO) in the treatment of patients with acute myocardial ischemia complicated by refractory cardiogenic shock. Methods The clinical data of 70 patients with acute myocardial ischemia complicated by refractory cardiogenic shock treated with VA-ECMO in the First Hospital of Lanzhou University from January 2022 to April 2023 were analyzed retrospectively. According to the success of VA-ECMO withdrawal, the patients were divided into success group (54 cases) and failure group (16 cases). The general data, Intraoperative condition, hemodynamic and biochemical indexes of the two groups were compared, and the independent risk factors affecting the clinical outcome were analyzed. Results The time of ECMO assistance in the success group was significantly shorter than that in the failure group (P < 0.05). There was no significant difference inother general information between the two groups(all P > 0.05). There was no significant difference in preoperative TIMI grade, number of diseased vascular branches, use of IVUS, ECG results and SYNTAX score between the two groups(all P > 0.05). Compared with those before treatment, arterial oxygen saturation (SaO2), left ventricular stroke volume (LVSV), left ventricular ejection fraction (LVEF), mitral annulus systolic velocity (Sa), aortic orifice forward flow spectrum (AV), velocity-time integral (VTI) and tricuspid annulus systolic displacement (TAPSE) increased significantly after ECMO plus PCI treatment (all P < 0.05). Left ventricular end systolic volume (LVESV) decreased significantly (P < 0.05). Compared with those in the failure group, the heart rate (HR), shock index (SI), blood lactic acid (Lac), C-reactive protein (CRP), aspartate aminotransferase (AST) and total bilirubin (TBIL) were lower in the success group (all P < 0.05). There was no significant difference in ECMO flow and SaO2 between the two groups(P > 0.05). Univariate logistic regression analysis showed that ECMO-supporting time, HR, Lac, CRP, AST and TBIL were the influencing factors of weaning failure in patients with acute myocardial ischemia complicated with refractory cardiogenic shock. Conclusion VA-ECMO combined with PCI can significantly improve cardiac function in patients with acute myocardial ischemia complicated by refractory cardiogenic shock.Echocardiographic parameters (LVESV, LVSV, LVEF, Sa, AV, VTI, TAPSE) and clinical indexes (HR, Lac, CRP, AST, TBIL) have certain clinical value for theprognosis.

Comparison of different blood vessels as markers in laparoscopic radical resection of right colon cancer
Ranhao ZHANG,Wenjuan QIAO,Mengwei SHI,Dongdong MU,Liansheng ZHENG
2024, 40(2):  225-230.  doi:10.3969/j.issn.1006-5725.2024.02.017
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Objective To compare the clinical efficacy and short?term prognosis of laparoscopic radical resection of right colon cancer guided by superior mesenteric artery and superior mesenteric vein. Methods 80 patients with right colon cancer of cT2?4 and/or N0?2M0 admitted from January 2020 to October 2022 were selected as the research objects, and they were randomly divided into observation group and control group, with 40 patients in each group. The observation group was treated with SMA?oriented laparoscopic radical resection of right colon cancer, while the control group was treated with SMV?oriented laparoscopic radical resection of right colon cancer. The curative effect and prognosis of the two groups were compared. Results There was no significant difference between the two groups in general condition, operation time, gastric tube placement time, recovery time of farting, postoperative fasting time, postoperative drainage time, postoperative nutritional index, total incidence of complications and postoperative hospitalization time(P > 0.05). The lymph nodes in the observation group were significantly more than those in the control group, and the difference was statistically significant(P < 0.05). In the observation group, the lymph nodes in the anterior and left side of superior mesenteric artery were examined (No.D3), and 273 lymph nodes were detected, and Seven patients (17.5%) were diagnosed with D3 metastasis, and 13 lymph nodes were positive (5.2%). Conclusion Laparoscopic radical resection of right colon cancer guided by superior mesenteric artery, without increasing the incidence of complications and high safety, can more thoroughly clean lymph nodes and reduce tumor recurrence, which is expected to significantly improve the prognosis of patients.

The Nomogram model was established for the risk assessment of intestinal colonization with neonatal CRKP
Xing HU,Qingrong LI,Jiang LI,Wei HE,Ping′an HE,Mei LV,Xu. YANG
2024, 40(2):  231-236.  doi:10.3969/j.issn.1006-5725.2024.02.018
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Objective To establish a Nomogram model for assessing the risk of intestinal colonization by Carbapenem?Resistant Klebsiella pneumoniae (CRKP) to determine the specific probability of colonization and adopt individualized prevention strategies for the purpose of reducing the occurrence of colonization and secondary infection of neonatal CRKP. Methods A total of 187 neonates hospitalized between January 2021 and October 2022 and diagnosed with CRKP colonization by rectal swab/fecal culture as well drug sensitivity identification 48 h after admission were assigned to the CRKP group. Another 187 neonates without non?CRKP colonization during the same period were set as the non?CRKP group. All the data of the two groups were used for a retrospective analysis. The caret package in R 4.2.1 was used to randomly divide the 374 cases into the model group and validation group at a ratio of 3∶1. Then the glmnet package in R 4.2.1 was used to conduct a LASSO regression analysis over the data from the model group to determine the predictive factors for modeling and the rms software package was used to build a Nomogram model. The pROC and rms packages in R 4.2.1 were used to examine the data, analyzing the consistency indexes (Cindex), receiver operating characteristic curves (ROC), and area under the curves (AUC) and performing the internal and external validation of the efficacy of the Nomogram model via the calibration curves. Results LASSO regression analysis determined eight predictors from the 35 factors probably affecting neonatal CRKP colonization: gender, cesarean section, breastfeeding, nasogastric tube, enema, carbapenems, probiotics, and hospital stay. The Nomogram model constructed using these eight predictors as variables could predict CRKP colonization to a moderate extent, with the area under the ROC curve of 0.835 and 0.800 in the model and validation group, respectively. The Hos?mer?Lemeshow test showed that the predicted probability was highly consistent with the actual probability (the modeling group: P = 0.678 > 0.05; the validation group: P = 0.208 > 0.05), presenting a higher degree of fitting. Conclusion The Nomogram model containing such variables as gender, cesarean section, breastfeeding, nasogastric tube, enema, carbapenems, probiotics, and hospital stay is more effective in predicting the risk of neonatal CRKP colonization. Therefore, preventive measures should be individualized based on the colonization probability predicted by the Nomogram model in order to keep neonates from CRKP colonization and reduce the incidence of secondary CRKP infections among them.

Drugs and Clinic Practice
Effects of simethicone on gastrointestinal hormones, intestinal floras and inflammatory process mediated by NLRP3 inflammasome in patients with irritable bowel syndrome
Xin LING,Jiaping QIAN,Dongtao SHI,Jun YANG,Peili FEI
2024, 40(2):  237-241.  doi:10.3969/j.issn.1006-5725.2024.02.019
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Objective To explore the effects of simethicone on gastrointestinal hormones, intestinal floras and inflammatory process mediated by NOD?like receptor protein 3 (NLRP3) inflammasome in patients with irritable bowel syndrome (IBS). Methods A total of 120 patients with IBS admitted to the hospital were prospectively enrolled as the research objects between January 1, 2021 and December 31, 2022, and they were randomly divided into control group (60 cases) and treatment group (60 cases). The control group was treated with compound eosinophil?Lactobacillus, while treatment group was additionally treated with simethicone. The curative effect after treatment, scores of gastrointestinal symptom rating scale (GSRS), levels of somatostatin (SS), vasoactive intestinal peptide (VIP), NLRP3 inflammasome, interleukin?8 (IL?8) and interleukin?1β (IL?1β), counts of intestinal floras before and after treatment, and safety during treatment were compared between the two groups. Results After treatment, total response rate of treatment group was higher than that of control group (91.67% vs. 76.67%, P < 0.05). After treatment, GSRS scores in both groups were decreased, which were lower in treatment group than control group (P < 0.05). After treatment, levels of SS and VIP in both groups were decreased, which were lower in treatment group than control group (P < 0.05). After treatment, counts of eosinophil?Lactobacillus and Bifidobacteria were increased in both groups, the difference was statistically significant (P < 0.05), but there was no significant difference in counts of intestinal floras between the two groups (P > 0.05). After treatment, levels of NLRP3 inflammasome, IL?8 and IL?1β were decreased in both groups, the difference was statistically significant (P < 0.05), but there was no significant difference between the two groups (P > 0.05). During treatment, there was no significant difference in side effects between the two groups (P > 0.05). Conclusion Simethicone can significantly improve response rate of treatment, improve gastrointestinal symptoms and gastrointestinal hormones in IBS patients, which has no significant effects on intestinal floras and inflammatory process mediated by NLRP3 inflammasome, with good safety.

Efficacy of ivabradine combined with levosimendan in patients with acute myocardial infarction complicated with heart failure
Xian WEN,Xianfeng ZENG,Ruiya SU
2024, 40(2):  242-247.  doi:10.3969/j.issn.1006-5725.2024.02.020
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Objective To observe the efficacy of ivabradine combined with levosimendan in patients with acute myocardial infarction complicated with heart failure. Methods A total of 78 patients with acute myocardial infarction complicated with heart failure admitted to the hospital from May 1, 2020 to December 31, 2022 were selected and divided into control group (n = 39) and study group (n = 39) by random number table method. In addition to basic treatment,the control group received levosimendan, and the study group ivabradine and levosimendan. The treatment period of both groups was 4 weeks. Compare two groups of patients' vital signs, clinical curative effect and heart function index, serological indexes, inflammatory factors and security. Results Compared with before treatment, the systolic blood pressure, diastolic blood pressure and heart rate of the two groups were decreased after treatment (P < 0.05), and the systolic blood pressure, heart rate, diastolic blood pressure and heart rate of the study group were significantly decreased compared with the control group (P < 0.05). Compared with the control group, the total effective rate of the study group was significantly higher (P < 0.05). Compared with before treatment, the levels of CO and LVEF were increased (P < 0.05), while the levels of LVEDV and LVESV were decreased (P < 0.05). Compared with the control group, the levels of CO and LVEF in the study group were higher (P < 0.05), and the levels of LVEDV and LVESV in the study group were lower (P < 0.05). Compared with before treatment, the levels of cTnI, sST2 and NT-proBNP in both groups were decreased after treatment (P < 0.05), and the serum levels of cTnI, sST2 and NT-proBNP in the study group were significantly decreased compared with the control group (P < 0.05). Tumor necrosis factor α (TNF-α), myeloperoxidase (MPO) and highly sensitive C-reactive protein (hs-CRP) were all decreased after treatment in the two groups (P < 0.05), and those in the study group were much lower (P < 0.05)No difference between the incidence of adverse reactions to the total contrast the two groups (P > 0.05). Conclusion Levosimendan combined with ivabadinehave a definite effect on patients with acute myocardial infarction complicated with heart failure for the improved cardiac function, reduced inflammation, regulated serum sST2, cTnI, and NT-proBNP level. It is also safe and reliable

Medical Examination and Clinical Diagnosis
Values of different DIC scoring systems in early diagnosis and prognosis prediction of coagulation dysfunction in sepsis patients
Fangmin GENG,Yuandan HE,Wenjuan LI,Qianqian LIU,Hongwei ZHANG,Zhangping LU,Lianhua WEI
2024, 40(2):  248-252.  doi:10.3969/j.issn.1006-5725.2024.02.021
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Objective To evaluate five types of DIC scoring systems based on sepsis patients, to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients, and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC. Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1, 2019 to December 31, 2021 were retrospectively analyzed within 24 hours. Five types of DIC scoring systems were used to score, and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared. The ROC curves of five DIC scoring systems were established to evaluate the accuracy of DIC in sepsis patients. Results The fatality rate of sepsis increased with the severity of sepsis (P < 0.05). There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems (P < 0.05). JMHW, CDSS and part of ISTH were detected in JAAM cases, while ISTH was detected in non-dominant ISTH cases. ISTH, JAAM, JMHW, CDSS, and non-dominant ISTH5 scoring systems were used to diagnose DIC, and absence of full health restoration and death were 3.0, 3.8, 4.2, 3.9, and 3.0 times higher than non-DIC cases, respectively. Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis. CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

Investigations
Epidemiological study on common congenital heart disease in children in ethnic minority areas in southeastern Guizhou and influencing factors of delayed medical treatment
Xiuhua YANG,Yongling YANG,Zhen ZHANG,Jianjun LONG,Tao CHENG,Jian CHEN,Cunhao TIAN
2024, 40(2):  253-260.  doi:10.3969/j.issn.1006-5725.2024.02.022
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Objective To conduct an epidemiological survey of common congenital heart disease (CHD) among children in ethnic minority areas in southeastern Guizhou and to explore the influencing factors of delayed medical treatment. Methods From January 2019 to July 2022, 18 850 children aged 3 months to 14 years in Qiandongnan Miao and Dong Autonomous Prefecture were selected; 105 children with CHD were included in the training set, and they were divided into delayed group (80 cases) and non-delayed group (25 cases) according to whether or not to delay medical treatment. In addition, children with CHD (35 cases) from July 2022 to December 2022 were included in the validation set. The general data of the subjects in the two groups were compared and analyzed. Multivariate logistic regression was performed and risk scoring model was constructed. Results The prevalence of CHD in 18 850 children was 5.57‰ (105/18 850), with the highest prevalence in Liping County, and the lowest in Huangping County. The proportion of children with secondary atrial septal defect was the highest, and that of the aortic valve malformation was the lowest. Among the complex cases of CHD, the proportion of children with single type was the highest, and that of children with three or more types were the lowest. Among children with CHD, the rate of delayed medical treatment was 76.19% (80/105). The median delay in medical treatment was 12 months, with an average of (18.78 ± 4.77) months. Multifactor logistic regression analysis showed that heart murmur (level 2 ~ 3), less-educated (primary and secondary school) guardian, family per capita income < 2 000 yuan, and frequent drinking of the guardian were independent risk factors for delayed medical treatment (P < 0.05), and commercial settlement of medical expenses was independent protective factor (P < 0.05). Risk scoring model divided the children into three groups: low risk (≤ 80 points), medium risk (> 80 points and ≤ 134 points) and high (> 134 points) risk group. The evaluation of the model show that it was accurate, effective, safe, and reliable. Conclusion The highest prevalence is observed in Liping County. The proportion of children with secondary atrial septal defect and the proportion of children with single type are the highest. Delayed medical treatment is found in most of the children with CHD. Cardiac murmur, education background of the guardian, per capita family income, guardian alcohol consumption, and medical expense settlement method are all independent influencing factors for delayed medical treatment.

Comprehensive evaluation of TCM resource allocation in Guangzhou community using TOPSIS and RSR
Huili YUAN,Bo XIAO,Guang OUYANG,Ling YANG
2024, 40(2):  261-266.  doi:10.3969/j.issn.1006-5725.2024.02.023
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Objective To comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in grassroots community health service centers in Guangzhou in 2022. Methods Based on the index system of traditional Chinese medicine resource allocation (community health service center) in Guangzhou, MATLAB R2021a and SPSS 27 software were used to comprehensively evaluate the current situation of traditional Chinese medicine resource allocation in 116 community health service centers in Guangzhou by TOPSIS method and RSR method. Results The allocation of TCM resources in 5 communities, including Xiaoguwei Street Community Health Service Center in Panyu District, Guangzhou City, Dadong Street Community Health Service Center in Yuexiu District, Guangzhou City, Fengyuan Street Community Health Service Center in Leiwan District, Guangzhou City, was evaluated as “excellent”, and the allocation of TCM resources in 4 communities was rated as “poor”. In addition, 27, 53 and 27 community health service centers were rated as “upper middle”, “medium” and “lower middle” respectively. Analysis of variance showed that the difference was statistically significant (F = 231.268, P < 0.001). Conclusion TOPSIS method combined with RSR method can better evaluate the allocation of TCM resources in grass?roots communities: The allocation of TCM resources in grass?roots communities in Guangzhou is generally good, but there are still significant differences among different communities. In the future, health administrative departments at all levels in Guangzhou can rationally allocate resources according to the differences of different communities and better improve the capacity building of traditional Chinese medicine service in grassroots communities.

Clinical Nursing
Effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery
Peiqian LAI,Pei HU,Hongshen WANG,Yanhua ZHENG,Meiyan LAN,Shaohua CHEN
2024, 40(2):  267-271.  doi:10.3969/j.issn.1006-5725.2024.02.024
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Objective To observe the effect of acupoint sticking therapy along meridians on gastrointestinal function recovery in patients after lumbar internal fixation surgery. Methods From January 2020 to March 2022, 125 patients with lumbar degenerative diseases were admitted to our hospital's Department of Orthopaedics and divided into two groups: control (n = 62) and acupoint sticking therapy (n = 63). The control group received standard postoperative care for lumbar internal fixation, while the experimental group received routine care based on acupoint sticking therapy along meridians. The NVAS scores for postoperative nausea and vomiting, abdominal distension and pain, bowel sound, initial exhaust, and defecation time were compared between the two groups. Results Both groups experienced gastrointestinal problems to varied degrees following surgery. The experimental group had significantly lower rates of nausea, NVAS score, vomiting grade, abdominal distension, return to normal bowel sounds, and time of first exhaust and bowel movement compared to the control group (P < 0.05). However, there were no significant differences in abdominal pain and abdominal circumference (P > 0.05). There were no adverse reactions in either group. The incidence of postoperative abdominal distension, nausea and vomiting in the observation group was lower than that in the control group, and the difference was statistically significant (P < 0.05). Conclusion Acupoint sticking therapy along meridians could accelerate the recovery of gastrointestinal function of patients after lumbar internal fixation, promote rapid recovery after surgery, and improve quality of life.

Reviews
Landmark Achievements in Treating Solid Tumors with Immune Checkpoint Inhibitors
Yuqiao ZHANG,Weijian MEI
2024, 40(2):  272-277.  doi:10.3969/j.issn.1006-5725.2024.02.025
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Tumor metastasis is a primary cause of death among solid tumor patients. Interventions such as chemotherapy with cytotoxic drugs and other targeted therapies focusing on specific genes or tumorigenesis can induce tumor shrinkage in most cases. However, these interventions do not substantially prolong the lives of patients. In recent years, immunotherapy has made significant breakthroughs in treating solid tumors with the introduction of immune checkpoint inhibitors (ICIs), following the clinical use of Ipilimumab, the first anti?tumor drug with ICIs initially approved in 2011. Currently, four types of ICIs including CTLA?4, PD?1, PD?L1, and LAG3 have been clinically applied and have demonstrated specificity towards more than 20 types of solid tumors. The significance of ICIs lies in their superiority to conventional drugs in three aspects: (1) They can prolong the survival of late?stage patients and even achieve “clinical cure”; (2)They allow patients with rare tumors access a pan?tumor treatment based on specific biomarkers; and (3)They can free a majority of patients from invasive surgical approaches to preserve organ functions, thereby improving patient’s quality of life. This article provides a summary of multiple clinical research projects and explores the clinical evidence derived from the notable achievements related to the three advantages.

Research progress on the relationship between m6A methylation modification and acute kidney injury
Lili TANG,Xinyu WANG,Jie ZHANG,Yue ZHAO,Xiaoyue LI
2024, 40(2):  278-282.  doi:10.3969/j.issn.1006-5725.2024.02.026
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Acute kidney injury(AKI) is a global public health problem with high morbidity, high mortality and costly treatment cost. The pathogenesis of AKI is very complex, and the treatment strategies for AKI are limited, then it is very matter to explore the pathophysiological mechanism and potential therapeutic targets of acute kidney injury. N6-methyladenosine(m6A) is the most abundant and extremely conservative epigenetic modification in eukaryotic, which is a dynamic and reversible process involving in splicing, nuclear export, translation, stability, and higher structure of RNA, and regulated by three regulatory factors: methyltransferase, demethylase and methylated reading protein. Current studies have found that m6A plays an important regulatory role in AKI and can be a potential therapeutic target for AKI. In this review, we provide a brief description of m6A and summarize the impact of m6A on AKI and possible future study directions for this research.