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10 September 2023, Volume 39 Issue 17
Clinical Advances
Application of ctDNA in gynecological malignant cancer
Ping YIN,Hanzi XU,Chenjing. ZHU
2023, 39(17):  2153-2158.  doi:10.3969/j.issn.1006-5725.2023.17.001
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As a non-invasive way to obtain tumor samples, liquid biopsy has the advantages of minimal invasiveness and repeatability. Through liquid biopsy, corresponding circulating tumor DNA can be obtained, including point mutations, copy number variations, and DNA methylation. It has been approved for the diagnosis and treatment of various malignant tumors. This article reviews the research and application of circulating tumor DNA, a liquid biopsy technology, in the early diagnosis, risk assessment of recurrence and metastasis, treatment guidance, and dynamic follow-up and monitoring of gynecological malignancies.

Construction and preliminary investigation of a colonic organoid culture system
Jiaqi CHEN,Xiuli SHI,Xueyun HUANG,Na. WU
2023, 39(17):  2159-2163.  doi:10.3969/j.issn.1006-5725.2023.17.002
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Colonic organoids are cultured in vitro from pluripotent stem cells or intestinal stem cells, which can effectively mimic the morphology and physiological functions of colon tissue, providing an effective in vitro model for the study of various colon diseases. This paper reviews the construction and initial investigation of the culture system of colonic organoids, aiming to provide a reference for researchers related to colonic organoids.

Basic Research
Effect of lncRNA NEAT1 on palmitic acid⁃induced LO2 cell injury and inflammatory response through regulation of NF⁃κB signaling pathway
Yunchun XU,Xinya YU,Yazhi WANG,Yuanying SHEN,Le. GUO
2023, 39(17):  2164-2170.  doi:10.3969/j.issn.1006-5725.2023.17.003
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Objective To explore the role and mechanism of lncRNA NEAT1 in palmitic acid-induced injury and inflammatory response of LO2 cells by regulating NF-κB signaling pathway. Methods LO2 cells were treated with palmitic acid for 24 h. Oil red O staining and triglyceride (TG) test were done to detect lipid accumulation, CCK8 assay was done for cell viability, and ALT and AST were tested for detecting hepatocyte injury. The expression of lncRNA NEAT1 was detected by RT-qPCR, the expression of inflammatory cytokines TNF-α, IL-1β and IL-6 in intracellular and culture supernatants were determined by RT-qPCR and ELISA and the expression of NF-κB signaling pathway-related proteins was detected by Western blot and immunofluorescence. Results In the palmitic acid-treated LO2 cells, the lipid accumulation was increased, the cell viability was decreased, the levels of ALT and AST were increased. Meanwhile, the expression of inflammatory cytokines TNF-α, IL-1β and IL-6 was increased and the expression of lncRNA NEAT1 was upregulated (P < 0.05). After overexpression of lncRNA NEAT1, the levels of ALT, AST, TNF-α, IL-1β, IL-6 were even more increased, the cell viability was significantly reduced. Contrarily, inhibition of lncRNA NEAT1 resulted in the opposite effect (P < 0.05). In addition, NF-κB signaling pathway was activated in the LO2 cells induced by palmitic acid and IKBα expression was decreased and phosphorylation of NF-κB p65 was increased. Then the overexpress of lncRNA NEAT1 further promoted the degradation of IKBα protein and increased NF-κB p65 phosphorylation into the nucleus, and contrarily, inhibition of lncRNA NEAT1 resulted in the opposite effect (P < 0.05). Conclusion The up-expressed lncRNA NEAT1 in LO2 cells induced by palmitic acid can promote cell injury and inflammatory response by way of activating NF-κB signaling pathway.

Proteomic analysis of exosomes derived from Porphyromonas gingivalis ⁃infected esophageal squamous cancer cells
Lanlan CUI,Ge ZHANG,Banglao. XU
2023, 39(17):  2171-2175.  doi:10.3969/j.issn.1006-5725.2023.17.004
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Objective To study the effect of Porphyromonas gingivalis (Pg) on the expression of exosomes (Ex) proteins secreted by Eca109 cells and their related functions and signal pathways. Methods The exosome proteins of Eca109 infected and uninfected by Pg were identified by Nano?LC?MS/MS. The differential proteins were selected by bioinformatics, and analyzed by GO enrichment and KEGG pathway. Results A total of 729 and 952proteins were identified in Pg?Ex and in Ex. Compared with Ex, 387 proteins were up?regulated and 294 proteins were down?regulated in Pg?Ex. These differential proteins are involved in biological processes such as cell proliferation, differentiation, adhesion, migration, angiogenesis,chemotaxis and immune response.They are enriched in Central Carbon Metabolism in tumor, PI3K?Akt signal pathway, HIF?1 signal pathway, Rap1 signal pathway,gap junction, Ras signal pathway, mTOR signal pathway, insulin signaling pathway, cGMP?PKG signaling pathway, ECM receptor interaction, chemokine signaling pathway, VEGF signaling pathway,etc. Conclusion It may indicate that Pg regulate tumor cell proliferation and migration, angiogenesis, immune response and thus participating in the development of esophageal cancer.

Preliminary study on the mechanism of TMEM39A in primary biliary cholangitis
Xiaotong SUN,Chongxu HAN,Chan WANG,Chuanli REN,Mingming. ZHANG
2023, 39(17):  2176-2182.  doi:10.3969/j.issn.1006-5725.2023.17.005
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Objective To explore the mechanism of TMEM39A in primary biliary cholangitis. Method In order to study how TMEM39A regulates the expression of autophagy in primary biliary cholangitis, human hepatobiliary cancer cell RBE was selected for study. Human hepatobiliary cancer cells were treated with the hydrophobic bile acid glycine deoxycholic acid (GCDC) into three groups: control group, 500 μmol/L group and 1 000 μmol/L group. Cell counting kits (CCK-8), cell cloning, cell scratching, and Hoechst staining assays were used to detect cell viability, proliferation, wound healing rates, and apoptosis. qPCR detected TMEM39A mRNA expression in cells; Western Blot detects protein expression of TMEM39A and LC3. Results Compared with control group, cell viability, proliferation and wound healing rate were decreased in 1 000 μmol/L group, while apoptosis was the most obvious. In the constructed model of primary biliary cholangitis, overexpression of TMEM39A promoted LC3 expression. Conclusion The increased expression of TMEM39A leads to enhanced autophagy of bile duct cells and bile duct damage, which may be one of the mechanisms causing primary biliary cholangitis.

Impacts of circLRP6 on cisplatin resistance to esophageal squamous cell carcinoma by regulating miR⁃125a⁃5p/MCL1 axis
Pingping LIN,Fubo LI,Dongjuan WANG,Yan GUO,Yi. DONG
2023, 39(17):  2183-2189.  doi:10.3969/j.issn.1006-5725.2023.17.006
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Objective To investigate the impacts of circular RNA lipoprotein receptor 6 (circLRP6) on cisplatin (CDDP) resistance to esophageal squamous cell carcinoma (ESCC) and its relevant potential molecular mechanism. Methods CDDP?resistant cell lines of KYSE30 (KYSE30/CDDP?R) were established and divided into a control group, si?NC group, si?circLRP6 group, si?circLRP6 plus anti?NC group, and si?circLRP6 plus anti?miR?125a?5p group. The expression levels of circLRP6, miR?125a?5p and myeloid leukemia?1 (MCL?1) in tissues/cells were detected by RT?qPCR and Western blot. CCK?8 assay was applied to detect the CDDP sensitivity of KYSE30/CDDP?R cells, so was flow cytometry to detect apoptosis. Results mRNA levels of circLRP6 and MCL?1 were increased, while level of miR?125a?5p was decreased in ESCC cancer tissues/cells and CDDP?resistant cancer tissues (P < 0.001). CircLRP6 silencing was able to up?regulate miR?125a?5p, inhibit the expression of MCL?1, enhance the sensitivity of CDDP?resistant ESCC cells to CDDP in vitro and in vivo, and promote the apoptosis of CDDP?resistant ESCC cells. Inhibition of miR?125a?5p weakened the effects of circLRP6 silencing on CDDP resistance and apoptosis in CDDP?resistant ESCC cells (P < 0.05). circLRP6 could target and negatively regulate the expression of miR?125a?5p, and MCL?1 was the target of miR?125a?5p. Conclusion CircLRP6 silencing may enhance the sensitivity of CDDP?resistant ESCC cells to CDDP through the miR?125a?5p/MCL?1 axis.

Up⁃regulated miR⁃106b⁃5p in exosomes derived from pulmonary artery smooth muscle cells enhances Warburg effect of pulmonary artery endothelial cells and promotes arterial pulmonary hypertension
Ailifeire MAIMAITI,Jing GAO,Zixiang YU,Yitong. MA
2023, 39(17):  2190-2195.  doi:10.3969/j.issn.1006-5725.2023.17.007
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Objective To explore the mechanisms of inter-cellular communication between pulmonary artery smooth muscle cells and pulmonary artery endothelial cells in promoting the progression of arterial pulmonary hypertension (PAH). Methods Exosomes in peripheral blood of healthy individuals (HC) and PAH patients were collected and isolated, and miRNAs in the exosomes were determined by microarray and differential expression analysis. Primary human pulmonary artery smooth muscle cells (hPASMCs) and primary human pulmonary artery endothelial cells (hPAECs) were treated with normoxia or hypoxia in vitro. Bioinformatics analysis was performed to detect sequence interaction sites between miR-106b-5p and USP32. Adenovirus was transinfectedinto the hPASMCs of over-expressed/knocked-down miR-106b-5p, or into the hPAECs of the over-expressed/knocked-down of PKM2. Dual luciferase reporter assay was used for confirming the sequence interaction of miR-106b-5p and USP32. The levels of USP32, PKM2, GLUT1, HK2 and LDHA were determined by Western blot. Results By microarray assay and differential expression analysis, the level of miR-106b-5p in the peripheral blood-derived exosomes was significantly up-regulated in the PAH group as compared with HC group. Compared with normoxia group cells, the level of miR-106b-5p was significantly up-regulated in the hypoxia-induced hPASMCs cells’ supernatant exomsomes, but not in the exosomes of hPAECs cells’ supernatant. MiR-106b-5p negatively regulated the expression of USP32. Compared with the miR-NC group/inhibitor-NC group,the expressions of PKM2, GLUT1, HK2 and LDHA were significantly enhanced/inhibited after miR-106b-5p mimic/miR-106b-5p inhibitor was treated with hPASMCs. Compared with shRNA-NT/vector group, PKM2 shRNA/PKM2-OE treatment in hPAECs significantly inhibited/enhanced intracellular expressions of PKM2, GLUT1, HK2, and LDHA (P<0.05). Conclusion HPASMCs enhances intracellular Warburg effect of hPAECs through up-regulating miR-106b-5p in exosomes, which has a potential role in promoting disease progression in arterial pulmonary hypertension.

MiR⁃499 protects hypoxia/reoxygenation (H/R) cardiomyocytes through Drp1⁃mediated mitochondrial autophagy
Jing WU,Zuqiong NIE,Wanling. YIN
2023, 39(17):  2196-2203.  doi:10.3969/j.issn.1006-5725.2023.17.008
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Objective To explore the protective effect of miR?499 on myocardial ischemia?reperfusion injury and its possible mechanism from the aspect of mitochondrial autophagy. Methods Myocardial cell H9c2(2?1) was induced by ischemia/reperfusion (I/R), and hypoxia/reoxygenation (H/R) myocardial cell model was established. The cells were treated with miR?499 mimics and/or P110. The cells were divided into BC group, I/R group, I/R + mi group, I/R + NC group, I/R + mi + P110 group and I/R + NC + P110 group. Cell proliferation was detected by CCK8 method. ROS, mitochondrial membrane potential and apoptosis were detected by flow cytometry. MDA, SOD and ATP contents were detected by their kit. The mRNA and protein expression levels of mitochondrial fusion, division and autophagy related genes Fis1, Mfn1, Parkin, LC3?Ⅱ, p62 and Drp1 were detected by qRT?PCR and Western blot. Mitochondrial autophagy was observed by transmission electron microscope. Results miR?499 mimics and/or P110 can reduce the proliferation inhibition rate and apoptosis rate of myocardial cells induced by I/R. The mitochondrial membrane potential decreased. The mitochondrial autophagy decreased and the ATP content increased. The gene and protein expression levels of Fis1, Parkin, LC3?Ⅱ and Drp1 decreased, while those of Mfn1 and p62 increased. The content of ROS and MDA in cells decreased, but the content of SOD increased. Conclusions miR?499 can reduce the occurrence of oxidative stress by reducing mitochondrial autophagy mediated by Drp1, thus protecting I/R?induced cardiomyocytes。

Clinical Research
Prognostic analysis of controlling nutritional status and prognostic nutritional index in patients with myelodysplastic syndromes
Quan′e ZHANG,Qiuni CHEN,Yue CHEN,Lijuan ZHANG,Jingjing MA,Xin ZHANG,Kankan CHEN,Chunling WANG,Zhengmei. HE
2023, 39(17):  2204-2209.  doi:10.3969/j.issn.1006-5725.2023.17.009
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Objective To explore the impact of controlling nutritional status and prognostic nutritional index on the prognosis of patients with myelodysplastic syndrome. Methods The clinical data of 119 patients with myelodysplastic syndrome treated in the department of Hematology of our hospital from March 2010 to December 2020 were retrospectively analyzed. The optimal cut-off point of observation index was calculated according to the receiver operating characteristic curve (ROC). CONUT score and PNI were grouped based on the cut-off points of 4 and 36.75, respectively, and the differences between age, gender, blood cell count and IPSS scores were analyzed.The prognostic factors were analyzed via univariate and Cox multivariate regression analyses. Results The univariate analysis revealed that age,platelet count, bone marrow blast cell count, IPSS scores and CONUT were risk factors for the prognosis of patients with MDS. The multivariate analysis revealed that bone marrow blast cell count (HR = 1.06,95%CI:1.01 ~ 1.12,P = 0.028) and CONUT (HR = 0.606,95%CI:0.39 ~ 0.95,P = 0.028) were independent prognosis risk factors of patients with MDS. Conclusions High CONUT score in newly diagnosed MDS patients indicates poor prognosis and is an independent risk factor for MDS prognosis, while PNI is not an independent risk factor for MDS prognosis.

Sdudy on the correlation and predictive value of chinese visceral adipose indexwith Obstructive sleep apnea in obesity
Peng ZHANG,Hua ZHANG,Yangxi HU,Xiaole YANG,Zhenhua LI,Yuna ZU,Guoyan LI,Huiqian. HE
2023, 39(17):  2210-2214.  doi:10.3969/j.issn.1006-5725.2023.17.010
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Objective By evaluating the correlation of chinese visceral adipose index (CVAI) and obesity-related evaluation indexes with Obstructive sleep apnea(OSA) and analyzing the influencing factors, we aim to screen out the diagnostic indexes of OSA in obesity and evaluate their diagnostic value. Methods A total of 460 obese patients admitted to bariatric surgery were enrolled,they were divided into OSA group and non-OSA group according to apnea hypopnea index (AHI), All subjects were measured for height, weight, neck circumference(NC), waist circumference(WC) and hip circumference(HC), examined for lipid levels, BMI, waist-to-height ratio(WHtR), waist-to-hip ratio(WHR) and CVAI were calculated according to the formula, The correlation between these indexes and AHI was analyzed and the influencing factors of OSA were screened out, The diagnostic value was evaluated by receiver operating characteristic curve (ROC) analysis. Results The prevalence of OSA in this study was 62%, Body weight, BMI, NC, WC, HC, WHtR, CVAI and AHI in OSA group were higher than those in non-OSA group, The lowest oxygen saturation and average oxygen saturation were lower than those in non-OSA group (P < 0.05). BMI, NC, WC,HC, WHtR, WHR, CVAI were positively correlated with AHI, and the correlation between NC and AHI was the strongest, followed by CVAI. Gender, NC and CVAI were independent influencing factors of OSA.ROC curve analysis showed that the area under curve (AUC) of NC and CVAI were 0.627 and 0.652 respectively.The critical value of NV for male was 47.75 cm, with 64.1% sensitivity and 78.9% specificity, The optimal threshold value for female was 39.75 cm, the sensitivity was 70.6%, the specificity was 51.8%; The critical value of CVAI for male was 266.19, with 67.2% sensitivity and 68.4% specificity, and the optimal critical value for female was 170.54, with 59.7% sensitivity and 75.9% specificity.The AUC value of the combined diagnosis was 0.653, higher than that of the single index, with 73.7% sensitivity and 53.7% specificity. Conclusion CVAI is closely correlated with OSA in obese patients, and can be used as a predictor of OSA in obese patients, the predictive value was higher when combined with NC.

Correlation of tacrolimus concentration and metabolic rate with prognosis in the early stage after heart transplantation
Lin GUO,Zhenzhen WANG,Xiangli ZHANG,Yunfei LIU,Mian ZHANG,Hua ZHENG,Chang′an. WANG
2023, 39(17):  2215-2220.  doi:10.3969/j.issn.1006-5725.2023.17.011
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Objective To evaluate the correlation of tacrolimus trough concentration, metabolic rate and their variability with postoperative infection, rejection and death in the early stage of heart transplantation. Methods The information of recipients who underwent heart transplantation in our hospitalwas reviewed, and the tacrolimus trough concentration (C0) monitoring value and tacrolimus dose were collected within 30 days after surgery. The mean C0 value, metabolic rate (C0/D) and their variability were calculated. The postoperative infection, rejection and death of recipients were followed up, and the correlation between early exposure of tacrolimus and these prognosis was analyzed. Results A total of 172 heart transplant recipients were finally included as research subjects. The mean and peak value of tacrolimus C0 had no statistical correlation with prognosis (all P > 0.05). The C0/D values of recipients with overall infection, hospitalized infection and rehospitalization due to infection were significantly higher than those without infection, and the differences were statistically significant (2.044, 2.432 and 2.816, P = 0.007、0.044 and 0.017, respectively). In terms of rejection and death, there was no statistical difference in C0/D value (P > 0.05). The subjects were divided into concentration < 10 ng/mL group (n = 132), 10 ~ 15 ng/mL group (n = 34) and > 15 ng/mL group (n = 6), there was no significant difference in postoperative infection, rejection and death (all P > 0.05). The SD values of C0/D in recipients with hospitalized infection, infection rehospitalization or overall infection were significantly higher than those without infection (Z = 2.044, 2.432 and 2.816, P = 0.041, 0.015 and 0.005, respectively). The SD value of C0/D in death recipients was also higher than that in survival recipients (Z = 2.255, P = 0.024). Conclusion Tacrolimus C0 is not significantly associated with rejection, overall infection, and death; tacrolimus slow metabolizers are more prone to postoperative infection than fast metabolizers; the variability of tacrolimus metabolic rate is related to the incidence of postoperative infection, and the higher variability of metabolic rate of tacrolimus is a risk factor for poor prognosis after heart transplantation.

Changes in serum sB7⁃H3 and CX3CR1 levels in patients with irreversible pulpitis and their clinical significance
Yuanyuan YUAN,Lu PAN,Shaolan.. ZHOU
2023, 39(17):  2221-2224.  doi:10.3969/j.issn.1006-5725.2023.17.012
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Objective To detect the changes of soluble B7-H3 (sB7-H3) and CX3C chemokine receptor 1 (CX3CR1) levels in patients with irreducible pulpitis and explore their prognostic value. Methods A total of 104 patients with irreversible pulpitis involved in the study, including 52 cases of acute pulpitis and 52 cases of chronic pulpitis. According to the treatment results, 83 cases with good prognosis were assigned as one group and 21 cases with poor prognosis as another group. Meanwhile, another 101 healthy individuals who underwent physical examination during the same period were enrolled as the health group. Enzyme-linked immunosorbent assay was applied to detect serum levels of sB7-H3 and CX3CR1. Results The serum levels of sB7-H3 and CX3CR1 in the case group were higher than those in the healthy group (P < 0.05). The serum levels of sB7-H3 and CX3CR1 in the acute pulpitis group were higher than those in the chronic pulpitis group (P < 0.05). The serum levels of sB7-H3 and CX3CR1 in the poor prognosis group before and after treatment were higher than those in the good prognosis group (P < 0.05) and the serum levels of sB7-H3 and CX3CR1 were statistically significant different across different time points, between the groups and in terms of interactions (P < 0.05). The proportion of patients with acute conditions in the poor prognosis group was higher than that in the good prognosis group (P < 0.05). SB7-H3 and CX3CR1 were independent risk factors for the poor prognosis in the patients (P < 0.05). Conclusion The levels of serum sB7-H3 and CX3CR1 in patients with irreversible pulpitis are elevated. They may become important indicators for evaluating the conditions and treatment effectiveness of irreversible pulpitis.

Effect of different antihypertensive therapy levels on combined cardiovascular events in elderly patients with hypertension
Hui HUANG,Jinhu SU,Bing. WU
2023, 39(17):  2225-2229.  doi:10.3969/j.issn.1006-5725.2023.17.013
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Objective To investigate the effect of different antihypertensive therapy levels on composite cardiovascular events in older patients with hypertension. Methods This retrospective study recruited 449 older patients with hypertension (65 ~ 95 years old) who were taking continuous antihypertensive treatment between January 2010 and January 2020. The patients were divided into two groups according to practical blood pressure data for at least one year: group1 224 cases (SBP 110 ~ 130 mmHg) and group 2 225 cases (SBP 130 ~ 150 mmHg). The primary composite outcome was a composite of acute coronary syndrome, stroke, acute decompensated heart failure, and death from cardiovascular causes. The hazard ratios, 95% confidence intervals, and P value were estimated using the Fine?Gray subdistribution hazard model. The Cox regression model was employed for deaths from any cause. To analyze the effect of two groups antihypertensive therapy levels on the risk of cardiovascular events. Results Primary composite outcome events occurred in 21 of 224 patients (9.3%) in group1(SBP 110 ~ 130 mmHg), as compared with 28 of 225 patients (12.4%) in group 2 (SBP 130 ~ 150 mmHg) (HR = 0.75, 95%CI: 0.61 ~ 0.94, P = 0.06). The incidence of primary composite outcome events was significantly lower in group1 than in group 2, with an absolute difference of 3.1 percentage points. The results for individual event of the primary composite outcomes also favored group1. acute coronary syndrome (HR = 0.71, 95%CI: 0.48 ~ 0.96), stroke (HR = 0.68, 95%CI: 0.46 ~ 0.95), acute decompensated heart failure (HR = 0.27, 95%CI: 0.08 ~ 0.98), cardiovascular death (HR = 0.57, 95%CI: 0.39 ~ 0.85), and all cause death (HR = 0.93, 95%CI: 0.54 ~ 0.97). The benefit of group1 was significantly better than group 2. Conclusion Systolic blood pressure of 110 ~ 130 mmHg significantly reduces the incidence of cardiovascular events in hypertensive patients over the age of 65 when compared to 130 ~ 150 mmHg.

Drugs and Clinic Practice
Efficacy and safety of PEG⁃rhG⁃CSF for preventing neutropenia after chemotherapy with doxorubicin plus carboplatin in epithelial ovarian cancer patients: A retrospective clinical study
Lin LIU,Runrong LI,Shipeng. GONG
2023, 39(17):  2236-2240.  doi:10.3969/j.issn.1006-5725.2023.17.015
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Objective Evaluate the value of PEG-rhG-CSF in preventing neutropenia in ovarian epithelial cancer patients after AC regimen chemotherapy. Method A retrospective analysis was conducted on 136 patients with ovarian epithelial cancer who received AC regimen chemotherapy at the Department of Obstetrics and Gynecology, Southern Medical University Nanfang Hospital. The observation group consisted of 87 patients who received prophylactic use of PEG-rhG-CSF after chemotherapy, while the control group consisted of 49 patients who did not use PEG-rhG-CSF. The independent sample T-test, analysis of variance, and Chi-square test were used to compare the differences in neutropenia, neutropenic fever, QOL-C30, liver and kidney function between the two groups. Results The incidence of grade 3-4 neutropenia and febrile neutropenia in the observation group was lower than that in the control group (5.5% vs. 15.9%, 0.8% vs. 2.8%), and the differences were statistically significant (P < 0.001); There was no statistically significant difference in the incidence of liver and kidney function damage between the observation group and the control group (3.4% vs. 4.0%, P > 0.05). No serious adverse reactions occurred between the two groups (P > 0.05). Quality of life assessment analysis found that the functional area score and overall health status score of the observation group were higher than those of the control group (67.89 ± 13.95 vs. 50.22 ± 15.17, 68.05 ± 17.09 vs. 48.74 ± 20.18), the difference was statistically significant (P < 0.05). Conclusion PEG-rhG-CSF has high efficacy and safety in preventing neutropenia after AC regimen chemotherapy for ovarian epithelial cancer, with mild adverse reactions, and can improve the quality of life of ovarian epithelial cancer patients undergoing AC regimen chemotherapy.

Clinical value of quantitative detection of serum HBsAg and HBeAg to evaluate the viral response of entecavir in patients with hepatitis B cirrhosis complicated with primary liver cancer
Xinyi ZHANG,Guoliang ZHANG,Guanglin. ZHANG
2023, 39(17):  2241-2247.  doi:10.3969/j.issn.1006-5725.2023.17.016
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Objective To explore the clinical value of quantitative detection of hepatitis B surface antigen (HBsAg) and hepatitis B virus E antigen (HBeAg) serum levels to evaluate the viral response (HBV?DNA) of entecavir in patients with hepatitis B cirrhosis complicated with primary liver cancer. Methods From April 2020 to July 2021, 80 patients with moderate liver cirrhosis complicated with primary liver cancer were treated in our hospital. According to whether virological response occurred at the 8th week of treatment, the patients were divided into response group (n = 47) and non?response group (n = 33). The correlations between serum HBsAg, HBeAg and HBV?DNA levels were compared before and after treatment. The value of serum HBsAg and HBeAg levels in predicting viral response was determined by receiver operating characteristic (ROC) curve. The 1?year survival rate was analyzed by Kaplan?Meier method. Results The serum levels of HBsAg and HBeAg were positively correlated with the level of HBV?DNA before treatment. There were significant differences in serum HBsAg and HBeAg levels at 8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks after treatment. At the 48th week of treatment, the maximum area under the ROC curve of viral response predicted by serum HBsAg level was 0.818 (95% CI:0.709 ~ 0.965). The best cut?off point was (40.63 ± 10.28) ng/mL. The sensitivity is 91.34%. The specificity is 71.93%. At the 8th week of treatment, the area under the ROC curve predicted by serum HBeAg level was up to 0.801 (95% CI:0.673 ~ 0.979). The best cut?off point was (53.38 ± 9.86) NCU/mL. The sensitivity is 88.52% and the specificity is 83.42%. The results of survival analysis showed that the 1?year survival rate of the response group was 87.31% higher than that of the non?response group 62.18%, and the difference was statistically significant (P < 0.05). Conclusion Serum HBsAg and HBeAg levels were correlated with viral response in patients with hepatitis B cirrhosis complicated with primary liver cancer treated with entecavir. Quantitative detection of serum HBsAg and HBeAg levels to evaluate the viral response of patients has high clinical value.

Efficacy and safety of Anlotinib combined with PD⁃1 blockades for extensive⁃stage small⁃cell lung cancer
Jianguo LI,Shuman LI,Hui. CHEN
2023, 39(17):  2248-2252.  doi:10.3969/j.issn.1006-5725.2023.17.017
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Objective To investigate the efficacy and safety of Anlotinib combined with PD-1 blockades in patients with extensive-stage small-cell lung cancer (ES-SCLC). Methods This study retrospectively analyzed the data of 36 patients with ES-SCLC who were treated with at least one previous systematic chemotherapy regimen. All the patients received Anlotinib plus PD-1 blockades therapy. Results Efficacy evaluation and safety analysis were conducted in all the patients. The best efficacy results showed objective response rate was 27.8% (95%CI:14.2% ~ 45.2%); disease control rate 80.6% (95%CI: 64.0% ~ 91.8%). The PFS and OS of the 36 patients were 4.6 months (95%CI: 3.1 ~ 6.1) and 9.3 months (95%CI: 3.3 ~ 15.3), respectively, indicating that overall adverse reactions were tolerate and controllable. Multivariate cox regression analysis for PFS indicated that ECOG performance status was the independent factor to predict PFS. Conclusion Anlotinib combined with PD-1 blockades regimen preliminarily demonstrates encouraging efficacy and tolerable safety for patients with ES-SCLC in real-world clinical practice.

Medical Examination and Clinical Diagnosis
Effect of contrast agent temperature on adverse effects of hysterosalpingo⁃contrast sonography
Ping YANG,Yue ZHONG,Yaping ZHANG,Xu FAN,Hong. SHI
2023, 39(17):  2253-2257.  doi:10.3969/j.issn.1006-5725.2023.17.018
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Objective To investigate the effect of contrast agent temperature on adverse reactions of transvaginal four?dimensional hysterosalpingo?contrast sonography (TVS 4D?Hycosy) with pain as the main manifestation. Methods Double?blind randomized controlled study. A total of 220 patients who underwent TVS 4D?Hycosy examination were randomly assigned (1∶1) to receive preheated contrast agent (38 ℃) and normal temperature contrast agent (22 ~ 26 ℃) respectively. The Stacey scoring scale was used to comprehensively evaluate pain, nausea, vomiting and other adverse reactions and NRS scoring scale were used to evaluate pain alone, and the occurrence of adverse reactions after intrauterine catheterization and during the examination was compared between the two groups. After the inspection, compare the proportion of people with persistent pain at 0 h, < 0.5 h, < 1 h, 1 ~ 24 h, and > 24 h between the two groups. Result There was no significant difference in Stacey adverse reaction score and NRS pain score between the two groups after intrauterine catheterization (Z = 0.231, -0.341, both P > 0.05). During the examination, the Stacey adverse reaction score and NRS pain score in the preheated group were lower than those in the room temperature group (Z = 2.906, 3.837, both P < 0.05), and the proportion of moderate and severe adverse reactions in the preheated group was lower than that in the room temperature group (χ2 = 7.502, P < 0.05), the difference between the two groups was statistically significant. After the examination, there was no significant difference in the proportion of people with persistent pain at 0 h, < 0.5 h, < 1 h, 1 ~ 24 h, and > 24 h between the two groups (χ2 = 0.141, 0.566, 0.697, 0.373, all P > 0.05). Conclusions Thermostatic preheated contrast agent reduces adverse reactions during the TVS 4D?Hycosy and is a simple and effective way to alleviate patient suffering.

Comparison of endoscopic features between colorectal sessile serrated lesions and hyperplastic polyps and establishment of predictive model
Yin LIN,Dongdong ZOU,Yilong WU,Min LIN,Tuo. YANG
2023, 39(17):  2258-2264.  doi:10.3969/j.issn.1006-5725.2023.17.019
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Objective To compare the endoscopic features between colorectal sessile serrated lesions and hyperplastic polyps, and to establish and assess a predictive model. Methods A total of 116 SSL lesions(94 patients) and 208 HP lesions(172 patients) which underwent colonoscopic lesion resection and confirmed by pathology from June 2019 to June 2022 at Fuding Hospital, Fujian University of Traditional Chinese Medicine were retrospective analyzed. The lesions were randomly divided into either a derivation sample or a validation sample using 1∶1 allocation according to the random number. In the derivation sample, SSL endoscopic features were used to establish a predictive model to distinguish between SSL and HP,in which predictors were identified by univariate and multivariate logistic regression analysis and predictive efficacy was evaluated by receiver operating characteristic (ROC) curve analysis. The predictive efficacy was assessed in the validation sample. Results Compared with HP,SSL was more common in the right colon with diameter > 5 mm and more likely to be manifested as: unclear boundary, irregular morphology, cumulus?like surface, surface mucus, varicose microvascular vessel and II?O pit pattern(P < 0.001). Diameter > 5 mm (OR = 7.717,95% CI:2.141 ~ 27.810,P = 0.002),surface mucus (OR = 12.063,95% CI: 3.925 ~ 37.072,P < 0.001) and unclear boundary (OR = 7.020,95% CI:2.118 ~ 23.260, P = 0.001) were predictors to diagnose SSL. Predictive model was built in the derivation sample with area under the ROC curve of 0.924(95% CI:0.884 ~ 1.000,P < 0.001). In the validation sample, the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of the predictive model were 93.10%, 94.23%, 93.83%, 90.00% and 96.08%, respectively. Conclusion Diameter > 5 mm, surface mucus and unclear boundary were predictors to diagnose SSL. Our predictive model have good predictive value, and it provide an important reference information for the endoscopists to make the correct diagnosis.

Modernization of Traditional Chinese Medicine
Research on the effect and mechanism of acupuncture combined with Chinese herbal cream mo based on the theory of agonistic point on patients with thoracic and dorsal myofascitis syndrome
Yong NIE,Junchen ZHU,Yingchun LI,Xingfu MA,Yi SU,Chao WANG,Yingzong XIONG,Fuyou. LI
2023, 39(17):  2265-2270.  doi:10.3969/j.issn.1006-5725.2023.17.020
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Objective To investigate the effects and mechanisms of acupuncture combined with Chinese herbal cream mo based on the agonistic point theory on patients withthoracic and dorsal myofascitis syndrome (TDMS). Methods One hundred patients with TDMS admitted to the second affiliated Hospital of anhui University of traditional Chinese medicine from March 2022 to March 2023 were collected as the study subjects, and were divided into 50 cases in the control group and 50 cases in the study group by digital randomization method, with the control group receiving Chinese herbal paste and moisturizing treatment and the study group receiving acupuncture combined with Chinese herbal paste and moisturizing treatment. Each group was treated once a day for 3 weeks. The total treatment efficiency of the two groups was compared, and the Oswestry Dysfunction Index Questionnaire (ODI), Short Form McGill Pain Questionnaire (SF-MPQ) scores, Beck Anxiety Inventory (BAI) scores and adverse effects were analyzed before and after treatment. Results Regarding the total treatment efficiency, the total treatment efficiency of the study group was 94.00%, which was statistically significant when compared with 78.00% in the control group (χ 2 = 5.316, P = 0.021). After treatment, ODI, BAI score, PRI, VAS, PPI and SF-MPQ total scores were lower in both groups than before treatment, and the study group was lower than the control group (P < 0.05). For adverse reactions, the overall incidence of 6.00% in the study group was not statistically significant when compared with 4.00% in the control group (P > 0.05). Conclusions Acupuncture combined with Chinese herbal cream mo based on the agonistic point theory has a positive therapeutic effect on patients with TDMS, and can effectively improve patients' functional impairment, anxiety and pain level with fewer adverse effects and high safety.

Reviews
Research progress of necroptosis in ophthalmology and clinical application of its inhibitors
Xinlin YAN,Xuan. LI
2023, 39(17):  2271-2276.  doi:10.3969/j.issn.1006-5725.2023.17.021
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Necroptosis is a major discovery in the field of cell death in recent decades. At present, in the field of ophthalmology, the activation of necroptosis pathway has been found from corneal diseases, glaucoma, retinal diseases and so on. In addition to Necrostatin-1(Nec-1), a necroptosis inhibitor targeting receptor-interacting protein1(RIP1), drugs such as GSK2399872A(GSK872), a receptor-interacting protein3(RIP3) inhibitor, and TC13172, a novel inhibitor targeting mixed lineage kinase domain-like protein (MLKL), have made major breakthroughs in cell death mechanisms. Currently in the field of ophthalmology, necroptosis inhibitors have demonstrated their protective effects in a variety of disease models. This article focuses on the molecular mechanism of necroptosis and the research results of its inhibitors in ophthalmology, discusses the potential of necroptosis as a new target for the treatment of ophthalmic diseases, and puts forward suggestions for its further research in the field of ophthalmology.

Research progress on relationship between cardiac amyloidosis and atrial fibrillation and its pathogenesis
Bo WU,Hengli LAI,Guowang SHEN,Zhenhuan CHEN,Yuan. LIU
2023, 39(17):  2277-2279.  doi:10.3969/j.issn.1006-5725.2023.17.022
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Cardiac amyloidosis (CA) is a myocardial disease caused by extracellular deposition of misfolded amyloid proteins in the myocardium. CA is associated with a higher prevalence of atrial fibrillation (AF), and myocardial amyloid infiltration can contribute to atrial electrical and structural remodeling through hemodynamic changes, increased ventricular wall stress, atrial amyloid deposition, and autonomic dysfunction, leading to the development and progression of AF. At present, the mechanism of CA in the pathogenesis of AF has not been elucidated. Therefore, exploring the relationship between CA and AF and the possible pathogenesis will help to deepen the knowledge of such patients and provide reference for clinical prevention and treatment.

Research progress in the regulation of allergic asthma by dendritic cells
Yunman ZHANG,Gonghua HUANG,Yanyan. WANG
2023, 39(17):  2280-2284.  doi:10.3969/j.issn.1006-5725.2023.17.023
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Allergic asthma is a chronic inflammatory airway disease characterized by over-activation of T helper 2 (Th2) cells in response to harmless air allergens. With high incidence and relapse rates, allergic asthma severely affects the life quality of patients. Dendritic cell (DC) plays important roles in initiating and maintaining Th2-mediated immune response during allergic asthma development,but the mechanism remains unclear. Therefore, it is important to study the function and underlying mechanism of DC in the pathogenesis of allergic asthma. We summarize the latest progress of immunometabolism, cytokines, and epigenetics in regulating DC function and DC-mediated Th2 immune responses, to direct the pathogenesis of allergic asthma. Further understanding the mechanisms by which DC regulates allergic asthma will provide new strategies for the treatment of allergic asthma.

Application of brain⁃computer interface in the rehabilitation of spinal cord injury
Feng WANG,Jinglong LI,Yuxiang. MAO
2023, 39(17):  2285-2288.  doi:10.3969/j.issn.1006-5725.2023.17.024
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Spinal cord injury can lead to severe sensory and motor dysfunction of limbs below the injury plane, which seriously affects the quality of life of patients. At present, the rehabilitation treatment methods for spinal cord injury are limited and the curative effect is not good. In order to seek a better treatment plan, some studies have tried to apply brain?computer interface technology to the rehabilitation treatment of spinal cord injury and made certain progress. A review published in 2020 provides a systematic overview of the field, but less on the latest theories, techniques, and materials. On this basis, this paper adds an overview of the latest research progress of BCI technology, in order to let readers know the latest research trends in this field. In addition, the clinical application and challenges of this technology are briefly described, and a new prospect for the research and development of this field is further proposed to provide some reference and theoretical support for subsequent research.