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10 October 2023, Volume 39 Issue 19
Symposiums:Tuberculosis topic
Treatment course of sensitive tuberculosis: From 24 months to 2 months
Liang LI,Yuhong. LIU
2023, 39(19):  2421-2423.  doi:10.3969/j.issn.1006-5725.2023.19.001
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The results of a clinical trial using an 8?week combination regimen of new drugs to treat sensitive tuberculosis, published by The New England Journal of Medicine in March 2023, have raised new expectations for further shortening the course of treatment for sensitive tuberculosis. Whether the treatment of sensitive TB must follow the standard 6-month chemotherapy regimen? This article reviews the historical evolution of the treatment plan for sensitive tuberculosis,and Propose thoughts and prospects for future treatment directions based on the current situation in China。

Progress in the research of tuberculosis transmission
Huizhong WU,Jinxing. HU
2023, 39(19):  2424-2427.  doi:10.3969/j.issn.1006-5725.2023.19.002
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Eliminating the source of infection, cutting off the transmission route and protecting susceptible population are the keys to control the prevalence of tuberculosis. In this paper, the research progress of tuberculosis transmission is briefly summarized from the aspects of pathogen, infection sources, transmission vectors and routes of transmission, high?risk population and its protection and blocking。

Feature Reports:Tuberculosis topic
Construction and function of an Lrp gene (Rv2779c) deletion mutant of Mycobacterium tuberculosis
Jifang ZHENG,Yuanyuan SHANG,Shengjuan BAO,Hairong HUANG,Suting. CHEN
2023, 39(19):  2428-2433.  doi:10.3969/j.issn.1006-5725.2023.19.003
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Objective To explore the function of Mycobacterium tuberculosis (Mtb) Rv2779c gene, an Rv2779c deletion mutant was constructed. Methods Using the genomic DNA of the Mtb reference strain H37Rv as the template, a 500 bp upstream and downstream fragment of Rv2779c gene for homologous recombination was amplified by PCR, and then constructed into the shuttle plasmid p0004s. The homologous recombinant plasmid p0004s was constructed into temperature-sensitive phasmid phAE159 and then packaged as phage. After the phage infection, the homologous recombinant element was integrated into the H37Rv genome. The positive clones were screened by hygromycin resistance marker in the recombinant element. The resistance-positive clones were identified by PCR. The growth differences between Rv2779c deletion mutant and H37Rv WT strain in 7H9 complete medium and high concentration rifampicin medium were compared. Results The recombinant plasmid p0004s-ΔRv2779c containing the upstream and downstream sequence of Rv2779c homologous recombinant arm was successfully constructed, and the plasmid was ligated with phAE159 which contained mycobacterium temperature sensitive element to obtain the recombinant phasmid. Finally, the successfully packaged phage infected H37Rv and the resistance positive clone was selected. PCR results showed that the Rv2779c gene of Mtbwas knocked out successfully. The knockout of Rv2779c had little effect on the growth of Mtb in normal medium, but significantly reduced the survival of Mtb in high concentrations of rifampin. Conclusion The Rv2779c deleted strain of Mtb was successfully constructed, which lays an important foundation for the functional study of Rv2779c gene. And preliminary studies revealed that this gene affected the growth of Mtb in rifampicin-containing medium.

Analysis of changes in serum expression levels of IL-6 during pulmonary tuberculosis treatment
Bei XIE,WanHua XU,Lan GONG,Yu YANG,Haiping DONG,ling WU,Fanrong MENG,Nan WANG,Zhihui LIU,Hua. LI
2023, 39(19):  2434-2439.  doi:10.3969/j.issn.1006-5725.2023.19.004
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Objective To explore the trend and influencing factors of serum IL-6 level in the treatment of pulmonary tuberculosis. Methods The serum of 56 patients with pulmonary tuberculosis was collected before treatment, 2 months of treatment (the end of the intensive period) and 6 months of treatment, and the expression level of IL-6 was measured by flow cytometry. Results The expression level of IL-6 in serum during treatment in tuberculosis patients tended to decrease, and the expression level was statistically significant (P = 0.000). ROC curve analysis showed that before treatment and 2 months of treatment, the subline area of IL-6 concentration difference in serum was 0.627, the cut-off value was 3.840, the sensitivity for discrimination was 71.40%, and the specificity was 51.80%. Binary logistic regression showed that whether the serum IL-6 concentration decreased to less than 3.840 pg/mL after 2 months of treatment was related to treatment cycle and age. The difference between the serum concentration of IL-6 before treatment was statistically significant between the group with or without cavitation, the treatment period group with 6 months and 12 months, and the group with no significant change in imaging lesions before treatment at 2 months, and the negative group with positive etiological test results before treatment. At 2 months of treatment, the difference between serum concentrations of IL-6 was statistically significant between different age groups, different treatment cycle groups, and the group with negative etiological test results before treatment and at 2 months of treatment. At 6 months of treatment, the difference between the serum concentration of IL-6 was statistically significant in the group with diabetes, in the group with different treatment cycles, and in the group with negative etiological test results at 6 months of treatment. ROC curve analysis showed that when the enrolled cases were limited to positive etiology before treatment, the off-line area of the difference in serum IL-6 concentration between 6 months of treatment and 2 months of treatment was 0.805, the cut-off value was 5.450, the sensitivity for discrimination was 81.25%, and the specificity was 75.00%. When the age of the enrolled cases was limited to 44 years and below, the off-line areas of IL-6 concentration differences in serum after 2 months of treatment and before treatment, 6 months of treatment and 2 months of treatment were 0.726 and 0.721, the cut-off values were 3.840 and 3.755, and the sensitivity and specificity were 70.59% and 67.65%, respectively. Conclusion During the treatment of pulmonary tuberculosis, the concentration of IL-6 in serum show a downward trend, and its level is related to whether the patient's lungs have cavities, etiological results, age, disease progression, and whether diabetes is present.

Diagnostic value and influencing factors of Xpert MTB/RIF assay for active tuberculosis in children
Guangdao CHEN,Saiddin Aziz.
2023, 39(19):  2440-2445.  doi:10.3969/j.issn.1006-5725.2023.19.005
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Objective To investigate the diagnostic value and influencing factors of Xpert MTB/RIF assay (Xpert) for active tuberculosis in children. Methods The sensitivity and specificity were compared among tuberculin skin test (TST), interferon gamma release assays (IGRAs) and Xpert among different ages and types of active tuberculosis in children, and the sensitivity of Xpert was compared among different types of specimens. Results A group of 231 children with active tuberculosis and another group of 216 without tuberculosis were included in the study. The sensitivity of Xpert for active tuberculosis was 62.78%, lower than that of IGRAs (P < 0.05), and the specificity was 100%, higher than those of IGRAs and TST (both P < 0.001). The sensitivity of Xpert was lower than that of IGRAs in the children younger than 5 years old (74.71% vs. 67.47%, P > 0.05), while the sensitivity of Xpert was significantly lower than that of IGRAs in the children older than 5 years old (58.26% vs. 84.62%, P < 0.001). The sensitivity of the pulmonary tuberculosis group was significantly higher than that of the extrapulmonary tuberculosis group (P < 0.001). There were statistical differences among the different types of specimens (P < 0.05),With the highest sensitivity of Xpert detected with bronchoalveolar lavage fluid (BALF). For the suspected pulmonary tuberculosis, the sensitivity of Xpert tested in the BALF was higher than that tested in the sputum (P = 0.012). For the suspected pulmonary plus extrapulmonary tuberculosis, the sensitivity of Xpert tested in therespiratory specimens was higher than that tested in the non-respiratory specimens (P = 0.004). Conclusion Xpert is effective in diagnosing childhood active tuberculosis, especially used in testing pulmonary tuberculosis and BALF of those suspected children younger than 5 years old. For pulmonary plus extrapulmonary tuberculosis, Xpert with respiratory tract specimens are first recommended.

Clinical Advances
Research progress on novel ultrasound techniques in assessing left ventricular myocardial function in patients with chronic aortic regurgitation
Huanhuan JIANG,Xinchun. YUAN
2023, 39(19):  2446-2449.  doi:10.3969/j.issn.1006-5725.2023.19.006
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Chronic aortic regurgitation is a common valvular heart disease in clinical practice, but how to determine the optimal timing of surgery remains a challenge. As one of the surgical parameters in patients with chronic aortic regurgitation, LVEF decreases significantly only when the myocardium is severely damaged, but the best time for surgical intervention has been missed at that point. In recent years, new ultrasound techniques have gained wide application in the assessment of left ventricular myocardial function in a range of valvular heart diseases. This article summarizes the advancement of new ultrasound techniques in the evaluation of left ventricular myocardial performance in patients with chronic aortic regurgitation and provides clues for clinical decisionmaking.

Basic Research
Effect of TGF-β/Smad signaling pathway regulated by total saponins of American ginseng on functional recovery of pelvic floor in rats with stress urinary incontinence
Lu LI,Xiujuan. LI
2023, 39(19):  2450-2455.  doi:10.3969/j.issn.1006-5725.2023.19.007
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Objective To explore the effect of TGF-β1/Smad signaling pathway regulated by total saponins of American ginseng on the functional recovery of pelvic floor in rats with stress urinary incontinence. Methods Sixty-five SD rats of SPF grade were selected, and 45 rats after modeling were randomly divided into model group, low-dose group and high-dose group with 15 rats each, and the remaining 15 rats without any treatment were used as control group. Rats in low-dose group and high-dose group were given total saponins of Panax quinquefolium according to the dosage of 50 mg/kg and 100 mg/kg respectively, while rats in control group and model group were given the same amount of physiological saline (15 mL). The pathological histology, pelvic floor function related indexes, urodynamics related indexes, bladder internal pressure related indexes, pelvic floor muscle surface electrical signals and the relative expression of TGF-β1/Smad signaling pathway protein were compared in each group. Results Compared with those in the control group, urethra rotation angle, bladder neck motion, residual urine volume, urine output, Smad2 and Smad3 expression were increased in the model group, the low and high dose group; vaginal resting pressure, systolic pressure, LPP, MBC, ALPP, urinary efficiency, Class Ⅰ and Class Ⅱ pelvic floor muscle fiber potential, TGF-β1, and Smad7 level were decreased (P < 0.05); Compared with those in the model group, vaginal resting pressure, systolic blood pressure, LPP, MBC, ALPP, urinary efficiency, class Ⅰ and Class Ⅱ pelvic floor muscle fiber potential, TGF-β1, Smad7 expression increased in the low and high dose group; urethral rotation angle, bladder neck motion, residual urine volume, urine output, Smad2 and Smad3 levels were decreased (P <0.05). Conclusion American ginseng total saponin could effectively improve pelvic floor function in rats with stress urinary incontinence, and the mechanism may be related to TGF- β1/Smad signaling pathway.

Construction of chronic myeloid leukemia K562 cell line with overexpression of human TCRP1 gene based on lentivirus vector and its biological function detection
Xiaorong LIU,Yue HE,Yan CHEN,Zefeng XIN,Xuwen DENG,Huifeng ZHONG,Yunsheng. CHEN
2023, 39(19):  2456-2460.  doi:10.3969/j.issn.1006-5725.2023.19.008
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Objective To construct the chronic myeloid leukemia (CML) K562 cell line with overexpression of human tongue cancer drug resistance related gene (TCRP1) by lentivirus vector and to test its biological function. Methods The recombinant plasmid of TCRP1 and the packaging plasmid were co-transfected into 293T cells, and the K562 cells were infected after the titer of the virus was determined. Puromycin was used to screen TCRP1 overexpression cell line K562/TCRP1, and the expression of TCRP1 was detected by fluorescence quantitative PCR and Western blot. The proliferation of K562/TCRP1 and its control cell line was detected by continuous cell counting method and CCK-8 method respectively. The drug sensitivity of the two cell lines to different concentrations of imatinib (IM) was analyzed. Results The TCRP1 lentivirus expression vector was successfully transfected into K562 cells. The results of fluorescence quantitative PCR and Western blot showed that the expression of TCRP1 in K562/TCRP1 cell line was significantly higher than that in the control group at the level of mRNA and protein. The results of continuous cell counting and CCK-8 methods showed that the proliferation of K562/TCRP1 cells were enhanced, and the IC50 value of IM-treated K562/TCRP1 cells was significantly higher than that of the control cells (P < 0.05). Conclusion The K562 cell line with overexpression of TCRP1 was successfully constructed using lentivirus vector, and we found that the overexpression of TCRP1 might enhance the proliferation and IM resistance of K562 cells, which provided a basis for further exploring the possible role of TCRP1 in the pathogenesis of chronic myeloid leukemia.

Mechanism of Sophocarpine on improving inflammation and mucous hypersecretion of human bronchial epithelial cells based on TLR4⁃NF⁃κB signaling pathway
Shengnan JIANG,Wenbing ZHI,Hong ZHANG,Xiaoting WANG,Tingting SUN,Zongren XU,Jing CHEN,Ye LI,Yang. LIU
2023, 39(19):  2461-2468.  doi:10.3969/j.issn.1006-5725.2023.19.009
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Objective To investigate the anti-inflammatory effect of sophocarpine (SC) in vitro and the potential mechanism of its anti-asthma effect based on the TLR4-NF-κB signaling pathway. Methods NCI-H292 cells were stimulated by Lipopolysaccharide (LPS) to induce inflammation model in vitro, and SC was given in different concentrations. The safe concentrations of LPS and SC on NCI-H292 cells were screened by MTT method, and the control group, LPS group (10 μg/mL LPS) and SC group (10 μg/mL LPS+ different concentrations of SC) were set up. The expression of mucin 5AC (MUC5AC) in cells and the secretion of Interleukin-6(IL-6) and Interleukin-8(IL-8) in the supernatant were detected by ELISA. The mRNA expression of MUC5AC, IL-6, IL-8, myeloid differentiation factor 88(MyD88) and nuclear factor-kappa B p65(NF-κB p65) in cells was detected by RT-PCR. The protein expression of TLR4, tumor necrosis factor receptor-associated factor 6 (TRAF6), p-p38 and p-p65 in cells and NF-κB p65 in nucleus was detected by Western blotting. Results MTT results showed that LPS and SC had no effect on cell viability in the concentration range of 0 ~ 10 μg/mL and 0 ~ 40 μg/mL. The results of ELISA showed that the content of MUC5AC in LPS group was significantly higher than that in control group (P < 0.01), and the levels of IL-6 and IL-8 in the supernatant of cells were also extremely significant increase (P < 0.01). Compared with the model group, the content of MUC5AC in SC group extremely significant reduction (P < 0.01), and the content of IL-6 and IL-8 in cell supernatant also significantly reduced (P < 0.01). RT-PCR results showed that the expressions of MUC5AC, IL-6, IL-8, MyD88 and NF-κB p65 mRNA in LPS group were extremely significant higher than those in control group (P < 0.01), however, the expression of MUC5AC, IL-6 and IL-8 mRNA in SC group decreased significantly (P < 0.05), and the expression of MyD88 and NF-κB p65 mRNA extremely significant reduction (P < 0.01). Western blotting results showed that SC could extremely significant reduction the expression of TRAF6, TLR4, p-p38 and p-p65 in NCI-H292 cells induced by LPS and the expression of NF-κB p65 protein in nucleus (P < 0.01). Conclusion SC may play an anti-asthmatic role by inhibiting TLR4-NF-κB signaling pathway, improving airway inflammation and mucous hypersecretion.

Mechanism of ADAMTS⁃5 in accelerating formation of neutrophil extracellular traps and worsening progression of intracranial aneurysm
Jun ZHANG,Wei WANG,Bangkui WANG,Jie. ZENG
2023, 39(19):  2469-2474.  doi:10.3969/j.issn.1006-5725.2023.19.010
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Objective To investigate the mechanism of ADAMTS-5 in accelerating the formation of neutrophil extracellular traps (NETs) and worsening the progression of intracranial aneurysm (IA). Methods IA mouse model was constructed. Adenovirus-mediated overexpression or knockdown ADAMTS-5 in arterial wall of the circle of Willis in the right cisterna of mice brain was conducted. Sixty mice were randomly divided into six groups of sham group, model group, shRNA-NT group, shRNA-ADAMTS-5 group, OE-vector group and OE-ADAMTS-5 group, with ten mice in each. H&E staining was used to analyze the infiltration of immune cells in arterial wall of the circle of Willis; and immunohistochemistry (IHC) to detect the expression of neutrophil markers MPO, neutrophil extracellular trap (NETs) markers H3Cit and ADAMTS-5 protein expression level in arterial wall of the circle of Willis. qPCR and western blot were used to analyze the expression of ADAMTS-5 mRNA and protein in arterial wall of the circle of Willis in sham group and model group. The expression of MPO, H3Cit, ADAMTS-5 and Collagen Ⅳ in arterial wall of the circle of Willis was detected by western blot. Results H&E staining showed that there were a large number of immune cells infiltrated in arterial wall of the circle of Willis in the model group, and IHC-MPO staining, IHC-H3Cit staining and IHC-ADAMTS-5 staining showed a large number of neutrophils infiltrated and NETs formed. ADAMTS-5 staining positive area overlapped with H3Cit staining positive area. Compared with that in the sham group, the expression of ADAMTS-5 mRNA and protein was higher in the model group (P < 0.05). Compared with the model group, knocking down/ overexpression ADAMTS-5 in arterial wall of the circle of Willis decreased/increased NETs formation (P < 0.05). Conclusion ADAMTS-5 plays an important role in driving formation of NETs and promoting disease progression of IA in mouse models.

Protective effects and the mechanism of miR⁃21⁃3p/p53 signaling pathway on renal function in mice with renal ischemia/reperfusion injury
Xiaolin LEI,Yanxiu LIU,Chan. ZHANG
2023, 39(19):  2475-2482.  doi:10.3969/j.issn.1006-5725.2023.19.011
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Objective To observe the effect of miR-21-3p on mice with renal ischemia / reperfusion (I/R) injury and to explore whether the renal protective effect is related to the regulation of apoptosis levels through miR-21-3p/p53 signaling pathway. Methods In vivo experiments were randomly divided into five groups: Sham, I/R, I/R + agomir, I/R + agomir + PIF, and I/R + PIF. Renal I/R injury model in vivo was established, overexpressing of miR-21-3p (agomiR-21-3p) in mice were constructed and treated with the p53 inhibitor Pifithrin-α (PIF). Dual-luciferase reporter assay was used to verify the interaction between miR-21-3p and p53. Serum levels of cystain C (Cys C), blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to reflect renal function of mice. Serum oxidative stress and inflammation indices were also determined, including tumor necrosis factor-alpha (TNF-α), Interleukin-1β (IL-1β), and high-sensitive c-reactive protein (hs-CRP). In addition, apoptosis rate of renal cells was visualized by TUNEL staining and the expression of apoptosis b-cell lymphoma-2 (Bcl-2), Bcl-2 assaciated X protein (Bax), p53 and caspase-3 were measured too. Results Compared with Sham group, the expression of miR-21-3p in I/R mice was significantly decreased. Compared with I/R group, the expression of miR-21-3p in the I/R + agomir group, the I/R + PIF group and the I/R + agomir + PIF group was significantly increased (P < 0.05), while the trend of p53 expression was opposite. Dual-luciferase reporter assay confirmed the interaction between miR-21-3p and p53. Compared with Sham group, the rate of cell apoptosis in all other renal tissues was increased; however, compared with the I/R group, the I/R + agomir, the I/R + PIF group and I/R + agomir + PIF groups were decreased, and the I/R + agomir + PIF group was the lowest (P < 0.05). Conclusions miR-21-3p could inhibit the development of apoptosis by targeting p53 expression, thus alleviating renal injury in mice with renal I/R.

Clinical Research
Regulatory role of miRNAs in the pathogenesis of osteoporosis induced by spinal cord injury
Cong CHEN,Huaijie XING,Min CHEN,Chaosheng ZENG,Qingjie. SU
2023, 39(19):  2483-2488.  doi:10.3969/j.issn.1006-5725.2023.19.012
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Objective To explore the regulatory role of immunoinflammatory mechanism regulated by tiny RNAs (miRNAs) in the pathogenesis of spinal cord injury-induced osteoporosis (CSCI-OP). Methods Thirty patients with CSCI-OP admitted to our hospital from July 2021 to July 2022 were selected as the observation group, fifty patients with senile osteoporosis were selected as the control group, and fifty healthy people were selected as the normal control group. The three groups were compared in terms of hormone indexes, inflammatory factors, miRNAs expression and bioinformatics analysis. The main factors affecting the pathogenesis of CSCI-OP patients were detected. Results Compared with the spinal cord injury group, the T and TNF-α levels were increased, and the E2, IL-6 and BLAP levels were decreased in the senile osteoporosis group (P < 0.05), but there was no significant difference in 25-OHD and PTH levels between the two groups (P > 0.05). Univariate analysis showed that the incidence of CSCI-OP was mainly related to age, sex, duration of spinal cord injury and diabetes mellitus (P < 0.05). Compared with the normal control group, the expression of IL-6 miRNA and BLAP miRNA in the control group and observation group was increased and the expression of TNF-α miRNA was decreased (P < 0.05). Conclusion MiRNAs can be effectively regulated in CSCI-OP. It can significantly slow down the occurrence and development of CSCI-OP through targeted immune inflammatory mechanisms.

Effects and satisfaction of combined spinal epidural anesthesia at different time points on labor analgesia in primiparous women
Minli HUANG,Zijing ZHANG,Hongfei DAI,Jiaxin LI,Shuzhen WU,Changping FANG,Zuen LIN,Lingling. WU
2023, 39(19):  2489-2494.  doi:10.3969/j.issn.1006-5725.2023.19.013
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Objective To compare the clinical effects of combined spinal epidural anesthesia (CSEA) at different times on the analgesic effect and satisfaction of primipara. Methods 504 primipara were included in this study. According to different degrees of cervical dilatation, the primipara with CSEA were divided into: Group Ⅰ (from labor to cervical dilation < 2 cm, n = 112 cases), group Ⅱ (2 cm ≤ Cervical dilation < 5 cm, n = 176 cases), group Ⅲ (cervix dilation ≥ 5 cm, n = 111 cases), control group (no neuraxial anesthesia for labor analgesia, n = 105 cases), in order to compare the effect of labor analgesia and satisfaction at different groups. Results The visual analogue scale (VAS) scores for group Ⅰ and group Ⅱ exceeded 3 points after 4 hours of labor analgesia, while the VAS scores for group Ⅲ exceeded 3 points after 3 hours of labor analgesia. The incubation period and the duration of the second stage of labor in group Ⅰ and group Ⅱ were longer than those in group Ⅲ and control group (all P < 0.05). The incidence of uterine atony in group Ⅰ, group Ⅱ and group Ⅲ were higher than those in the control group (all P < 0.05). The incidence of fever and urinary retention in group Ⅰ, group Ⅱ and group Ⅲ were higher than that in control group (all P < 0.05). The satisfaction levels of primiparous women in group Ⅰ and group Ⅱ were significantly higher than those in group Ⅲ and control group (all P > 0.05). Conclusion CSEA can effectively relieve pain for primiparous women after labor until the cervix is fully dilated. However, 4 hours after CSEA within 5 cm of the cervix, 3 hours after CSEA for cervix dilation larger than 5 cm, the anesthetic dose should be adjusted in time according to the pain score to achieve effective analgesia. It is important to observe and treat side effects related to anesthesia drugs in a timely manner to improve the satisfaction of primiparous women.

Diagnostic and Prognostic Value of HDAC4 and Fibrinogen/Albumin Ratio in Non⁃small Cell Lung Cancer
Jie ZHANG,Fanliang. MENG
2023, 39(19):  2495-2500.  doi:10.3969/j.issn.1006-5725.2023.19.014
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Objective To analyze the levels and prognostic value of histone deacetylase 4 (HDAC4) and the fibrinogen/albumin ratio (FAR) in the circulation of patients with non?small cell lung cancer(NSCLC) as well as the diagnostic value of these two factors combined. Methods The enzyme?linked immunosorbent assay was applied to determine the serum HDAC4 levels and detect the levels of fibrinogen, albumin, and carcinoembryonic antigen in 117 patients with NSCLC (lung cancer group), 50 patients with benign lung disease (reference group), and 50 healthy subjects (healthy control group). The HDAC4 and FAR levels were compared within the three groups. The associations of HDAC4 and FAR with the clinical features and the diagnostic and prognostic value of the two factors combined in NSCLC were analyzed. Results The levels of FAR and serum HDAC4 were significantly higher in the circulation of the NSCLC group compared with the reference and control groups (P < 0.05). HDAC4 and FAR were positively correlated with TNM stage, tumor size, lymph node metastasis, and distant metastasis (P < 0.05). HDAC4 combined with FAR had an AUC of 0.782, sensitivity of 59%, and specificity of 96% in non?small cell diagnosis. Survival analysis showed that higher HDAC4, FAR predicted shorter progression?free survival (PFS) (log?rank test, P < 0.05). Multifactorial analysis showed that HDAC4, FAR, distant metastasis, and treatment regimen were independent risk factors affecting the prognosis (PFS) of patients with non?small cell lung cancer (P < 0.05). Conclusions HDAC4 and FAR levels are elevated in the circulation of NSCLC patients, and the combination of HDAC4 and FAR has good clinical reference value for lung cancer diagnosis. Moreover, higher levels of HDAC4 and FAR are associated with poorer prognosis in NSCLC patients, suggesting their potential as prognostic indicators for evaluating the prognosis of NSCLC patients.

Effect of driving pressure guided ventilation strategy on cerebral oxygen saturation in infants with one lung ventilation during thoracoscopic surgery
Fuxiang HUANG,Haiyang LI,Dongmei QI,Weijian. HUANG
2023, 39(19):  2501-2505.  doi:10.3969/j.issn.1006-5725.2023.19.015
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Objective To investigate the effect of driving pressure (DP) guided ventilation strategy on regional cerebral oxygen saturation (SrcO2) in infants with one lung ventilation (OLV) during thoracoscopic surgery. Methods Sixty infants undergoing elective thoracoscopic surgery were randomly divided into control group (group C,n = 30)and driving pressure group (group DP, n = 30). Near?infrared spectroscopy was used to monitor SrcO2 during OLV. Cerebral oxygen desaturation (COD)was defined as SrcO2 decreased by more than 20% from baseline. The incidence of hypotension, time of ventilation rescue, the incidence of COD and its duration during OLV were recorded. MAP, HR, SrcO2, PEEP, airway peak pressure (Ppeak), static lung compliance (Cs) were recorded before (T1), 30 min after (T2) and 60 min after (T3)artificial pneumothorax, and results of arterial blood gas analysis on T1 and were T2 compared. Results There were no significant differences in the SrcO2 baseline, the mean SrcO2 during OLV, the incidence of hypotension and the incidence of COD between the two groups (P > 0.05). Times of ventilation rescue and COD duration in DP group were lower than those in C group(P < 0.05). There were no significant differences in MAP, HR, SrcO2, Ppeak, Cs, PaO2 and OI between the two groups at T1P > 0.05). Compared with T1, Ppeak increased and SrcO2 and Cs decreased in both groups at T2 and T3P < 0.05). Compared with group C, group DP had higher PaO2 and OI at T2, lower Ppeak and higher PEEP and Cs at T2 and T3P < 0.05). Conclusion DP guided ventilation strategy improved lung compliance, increased oxygen saturation and shortened the exposure of COD in infants during OLV.

Clinical efficacy of olecranon osteotomy approach vs lateral elbow approach for the treatment of transarticular coronal shear fracture of the distal humerus with open reduction and internal fixation surgery
Chengnian ZHANG,Xuecheng LI,Zheng ZHANG,Daijie. ZHANG
2023, 39(19):  2506-2510.  doi:10.3969/j.issn.1006-5725.2023.19.016
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Objective To compare the clinical efficacy of olecranon osteotomy approach vs lateral elbow approach for the treatment of transarticular coronal shear fracture of the distal humerus with reduction and internal fixation. Methods Sixty-two patients with transarticular coronal shear fracture of the distal humerus receiving open reduction and internal fixation surgery in our hospital from March 2016 to March 2021 were enrolled and assigned to two groups according to different surgical treatment methods. Control group (n = 32) received lateral elbow approach and treatment group (n = 30) received olecranon osteotomy approach. The general data, range of motion of the elbow joint, Mayo elbow performance score (MEPS), and complications between two groups were compared. Results No statistical difference was found in surgical duration and bleeding volume between the two groups (P > 0.05), while the incision length of treatment group was longer than that of the control group (P < 0.05). Compared with the control group, Mayo scale was higher in treatment group at postoperative 1, 6 and 12 months (P < 0.05). Compared with baseline data, the elbow flexion and extension range of motion improved in both groups at postoperative 12 months (P < 0.05). Treatment group was followed up for 12 to 24 months, with a mean of (14.8 ± 2.2) months, and the bone healing time was 6 to 10 weeks with a mean of (10.8 ± 2.7) weeks. In control group, the follow up time ranged from 12 to 31 months, with a mean of (15.5 ± 3.1) months, and the bone healing time was 8 to 21 weeks with a mean of (12.4 ± 3.2) weeks. Treatment group had notably decreased time on bone healing compared with control group (P < 0.05). No wound infection or vascular and nerve injury occurred in either group during the follow-up period. The incidence rate of joint stiffness, delayed fracture healing, traumatic arthritis, and heterotopic ossification yielded no statistical difference between the two groups (P > 0.05). Conclusion Compared with lateral approach, the treatment of transarticular coronal shear fracture of the distal humerus with reduction and internal fixation via olecranon osteotomy approach had better elbow joint recovery, less complications and better short-term effects.

Observation on clinical curative effect of 1 565 nm non⁃ablative fractional laser combined with silicone gel in the early treatment of head and face scar after emergency department trauma
Shuo WANG,Huaigu WANG,Banghong JIANG,Na HAN,Lei CUI,Ziye. BAI
2023, 39(19):  2511-2516.  doi:10.3969/j.issn.1006-5725.2023.19.017
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Objective To examine the effectiveness of a 1 565 nm non-ablative fractional laser combined with silicone gel in the early repair of scarring following head and face emergency trauma. Methods Randomly selecting 80 cases of early scar intervention patients who had experienced head and face emergency trauma at our hospital from September 2021 to December 2022 as research objects, we divided them into two groups and administered silicone gel application, as well as 1 565 nm Non-ablative fractional laser + silicone gel treatment. Each patient received 3 treatments with a 1-month interval between each treatment. Patients in two groups, each with 40 participants, were evaluated with the Patient Assessment Scale (PSAS), Observer Assessment Scale (OSAS), and the new Vancouver Scar Scale (VSS) prior to and two weeks after the last treatment. Results The results were documented in terms of patient satisfaction and adverse reactions during the treatment. We discovered that the PSAS, OSAS and VSS scores of the two groups of patients were lower post-treatment (P < 0.05) than before (P < 0.05). The control group score was also lower than the control group (P < 0.05). The control group satisfaction was 62.50%, while the observation group was 87.50%. The observation group was comprised of 2 individuals with pigmentation and 1 with pain, while the remainder were healthy. These two groups had distinct side effects. Conclusion It is found that both silicone gel and 1 565 nm non-ablative fractional laser can improve the scars of head and face emergency trauma patients, and the improvement effect of 1 565 nm non-ablative laser is affirmed, and the side effects are relatively small.

Immune mapping changes in the development of diabetic retinopathy
Xiaojun WU,Shimiao BU,Xiangting CHEN,Jun YU,Yong LIU,Yuehong ZHANG,Songqing XIN,Yufeng. LIU
2023, 39(19):  2517-2523.  doi:10.3969/j.issn.1006-5725.2023.19.018
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Objective To analyze the immunological regulation mechanism of the progression of diabetes to diabetic retinopathy. We used Flow cytometry to compare the differences of immune cell profiles in peripheral blood of healthy donors (HD), diabetic patients (DM), non-proliferative diabetic retinopathy patients (NPDR) and proliferative diabetic retinopathy patients (PDR). Methods Peripheral blood was collected from HD, DM, NPDR and PDR, and peripheral blood immune cells were isolated by density gradient centrifugation. The 13-color flow cytometry antibody was co-stained and detected by flow cytometry. Combined with Flowjo and its plug-in, the cells were analyzed by dimensionality reduction and clustering. Finally, Spearman correlation analysis and receiver operating characteristic (ROC) curve were used to evaluate the diagnostic value of peripheral blood immune cells in predicting the progression from DM to DR stage. Results Peripheral blood immune cells were divided into 10 groups. Among the innate immune cells, the number of mono-classical cells in DM and PDR was higher than that in healthy people (P < 0.05). In adaptive immune cells, B cells in DM and NPDR were higher than those in HD group (P < 0.05), while NKT and T cells were lower than those in HD group (P < 0.05). Compared with healthy people, B cells in PDR were increased (P < 0.05), but T cells were decreased (P < 0.05). In addition, B cells were positively correlated with each stage. And in the PDR stage, ROC curve analysis showed that the efficiency of B cells in predicting the progression of DM to DR was greater than that of other immune cells. Conclusion Differences were noted between the three stages of peripheral blood immune cell profiles in HD, DM and DR. In addition, B cells were positively correlated with each stage, and had the potential to predict the diagnostic value of disease progression.

Effect of transcatheter aortic valve implantation on severe aortic stenosis complicated with mitral regurgitation of different degrees
Xueya ZHANG,Yingchun GUO,Yiqiang YUAN,Xiaohu WANG,Xinyi WANG,Yuxin. CHEN
2023, 39(19):  2524-2528.  doi:10.3969/j.issn.1006-5725.2023.19.019
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Objective To study the effect of transcatheter aortic valve implantation (TAVI) on severe aortic stenosis (AS) complicated with mitral regurgitation (MR) of different degrees. Methods Retrospectively, 66 patients with severe aortic stenosis and TAVI surgery in Henan Provincial Chest Hospital from April 2020 to June 2022 were included and divided into group A (no regurgitation + mild regurgitation) and group B (moderate + severe regurgitation) according to presence or absence of MR as well as its severity. The changes in cardiac structure and function before and after operation and the effects of TAVI were compared between the two groups. Results The aortic valve peak gradient and aortic valve peak velocity in the two groups after operation were significantly improved compared with those before surgery (P < 0.05), but there was no statistical difference between the two groups (P > 0.05). In the moderate and severe mitral regurgitation group, the left atrial diameter [39.00(37.00,42.00)mm], left ventricular end diastolic diameter [47.00(41.00,58.00)mm], mitral regurgitation [2.90(2.40,4.70)cm2] and NT-ProBNP [2 567.80(1 196.87,3 344.90) pg/mL] were significantly lower than those before operation [41.00(38.00,48.00)mm], [55.00(44.00,60.00)mm], [7.60(5.10,11.00)cm2], [4 649.05(2 132.54, 9 333.30)pg/mL] (P < 0.05), and LVEF was higher than before surgery [50.00(42.00,61.00) vs. 45.00 (35.00, 62.00), P < 0.05]. Conclusion TAVI can be used for the treatment of patients with AS combined with MR of different degrees and it is beneficial for patients with moderate to severe mitral regurgitation as well.

Drugs and Clinic Practice
Remimazolam versus Propofol for children undergoing painless gastroscopy
Xue BAI,Hao LUO,Yayin HUANG,Junxiang HUANG,Yonghong TAN,Xingrong SONG,Bilian. LI
2023, 39(19):  2529-2533.  doi:10.3969/j.issn.1006-5725.2023.19.020
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Objective To compare the efficacy and safety of remimazolam vs propofol for children undergoing painless gastroscopy. Methods A total of 129 children aged 4 ~ 9 years, ASAⅠ-Ⅱ, BMI 18 - 30 kg/m2, scheduled for painless gastroscopy under intravenous general anesthesia were divided into two groups by random number table method: remimazolam group (R group) and propofol group (P group). Anesthesia was induced with sufentanil 0.2 μg/kg and penehyclidine hydrochloride 0.01 mg/kg. The patients in R group was given 0.5 mg/kg remimazolam and in P group was given 0.3 mg/kg propofol. The success rate of completing painless gastroscopy, heart rate, blood pressure, pulse oxygen saturation, sedation score, narcotrend index were recorded. The onset time, recovery time of orientation and adverse reactions were observed. Results The success rate of sedation in R group and P group was 82.8% and 90.8% respectively,with no statistically difference (P > 0.05). At the time of endoscopic insertion and the end of endoscopic operation, the narcotrend index value of R group was 84.7 ± 10.8, 86.4 ± 4.3, respectively, which was significantly higher than that of P group (58.9 ± 13.2 and 66.2 ± 5.0) (P < 0.05). The postoperative recovery time of R group was (14.2 ± 6.9) min, which was lower than that of P group (23.8 ± 6.7) min(P < 0.05). The incidence of injection pain in R group and P group was respectively 10.9% and 52.3%, with statistically significant difference(P < 0.05). And the other adverse reactions were not statistically significant (P > 0.05). Conclusion Both remimazolam and propofol could be safely and effectively used gastroscopy for children, and remimazolam made patients wake up quickly with a lower incidence of injection pain.

Effect of telmisartan combined with calcium dobesilate on hypertensive patients with type 2 diabetes mellitus on the blood pressure rhythm
Weiwei HU,Xiaorong LI,Chunhui TIAN,Zhifen LIU,Junqi. YING
2023, 39(19):  2534-2540.  doi:10.3969/j.issn.1006-5725.2023.19.021
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Objective To explore the effect of telmisartan combined with calcium dobesilate on hypertensive patients with type 2 diabetes mellitus (T2DM) on the blood pressure rhythm. Methods Patients with hypertension and T2DM who were treated in Hengshui people′s Hospital from January 2021 to December 2022 were selected as the study subjects. According to the principle of random grouping, the patients were divided into the control group (n = 115) and the observation group (n = 113). Patients in the control group were treated with telmisartan (40 mg once daily), while the patients in the observation group received additional calcium dobesilate treatment (0.5 g three times daily) on the basis of the treatment in the control group. Both groups of patients were treated for 12 months with follow-up visits every 3 months. The blood pressure indicators including 24-hour average systolic blood pressure (24 h SBP), 24-hour average diastolic blood pressure (24 h DBP), 24-hour average pulse pressure (24 h PP), daytime average systolic blood pressure (dSBP), daytime average diastolic blood pressure (dDBP), daytime average pulse pressure (dPP), nighttime average systolic blood pressure (nSBP), nighttime average diastolic blood pressure (nDBP) and nighttime average pulse pressure (nPP); blood glucose indicators including fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PG) and glycosylated hemoglobin (HBA1c); endothelial function indicators including endothelin-1 (ET-1), nitric oxide (NO) and vascular endothelial growth factor (VEGF); and occurrence of adverse reactions during the medication period were statistically analyzed for both groups of patients. Results Before treatment, there were no statistically significant differences (P > 0.05) in the various indicators (blood pressure, blood glucose, endothelial function) between the two groups of patients. After 3, 6, and 12 months of treatment, the blood pressure indicators (24 h SBP, 24 h DBP, 24 h PP, dSBP, dDBP, dPP, nSBP, nDBP, nPP), blood glucose indicators (FBG, 2 hPG, HBA1c), and endothelial function indicators (ET-1) were significantly lower than before treatment in both groups of patients, and the levels of these above-mentioned indicators in the observation group were lower than those in the control group, with statistically significant differences (P < 0.05). The levels of NO and VEGF in both groups of patients were significantly higher than before treatment, and the levels of NO and VEGF in the observation group were higher than those in the control group, with statistically significant differences (P < 0.05). The incidence of adverse reactions during the medication period showed no statistically significant differences between the two groups of patients (P > 0.05). Conclusion The combination of telmisartan combined with calcium dobesilate reduces blood pressure levels, regulates blood pressure rhythm, and improves endothelial function in patients with hypertension and T2DM, and shows favorable safety.

Medical Examination and Clinical Diagnosis
Values of serum HE4 combined with exosome miRNA-200a/200b/200c in the early diagnosis of CA125 negative ovarian epithelial carcinoma
Xiangbing JIANG,Lifei WANG,Chunlin WU,Feng LI,Donghua WANG,Xuemei. GAO
2023, 39(19):  2541-2545.  doi:10.3969/j.issn.1006-5725.2023.19.022
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Objective To investigate the value of serum human epididymal protein 4 (HE4) combined with micrornas (mirnas) -200a/200b/200c in exosomes in the early diagnosis of glycochain antigen 125 (CA125) negative epithelial ovarian carcinoma (EOC). Methods A total of 120 patients with CA125-negative EOC were selected as the study group, and 115 patients with ovarian epithelial benign tumor admitted during the same period were selected as the benign group. Another group of 107 healthy women who underwent physical examination in wuhan firsthospital were selected as the control group. The levels of HE4, CA125, miRNA-200a, miRNA-200b and miRNA-200c were compared among the three groups. The value of serum indexes in differentiating CA125-negative EOCs and benign ovarian epithelial tumors was analyzed by receiver operating characteristic (ROC) curve. Results The levels of HE4, miRNA-200a, miRNA-200b and miRNA-200c in the study group were significantly higher than those in the benign group and control group, statistically significant differences between the groups (P < 0.05). ROC analysis confirmed that serum HE4, miRNA-200a, miRNA-200b, and miRNA-200c could be used for the diagnosis of CA125-negative EOC. The combined diagnosis by HE4+miRNA-200a/b/c could obtain a higher area under the curve than the single or pair-based diagnosis (P < 0.05). Logistic stepwise regression analysis confirmed that, HE4 ≥ 163.110 pmol/L, miRNA-200a ≥ 2.700 2-△CT, miRNA-200b ≥ 1.665 2-△CT, miRNA-200c≥ 1.395 2-△△CT were the risk factors for CA125-negative EOC (P < 0.05). Conclusion Serum HE4, miRNA-200a, miRNA-200b and miRNA-200c can be used in the early diagnosis of CA125-negative EOC. The diagnosis with the four indicators combined has higher sensitivity and specificity.

High⁃frequency ultrasound for diabetic peripheral Neuropathy
Xiaoyi CHEN,Cuihua CHEN,Qiufeng WEI,Yubo. XIE
2023, 39(19):  2546-2550.  doi:10.3969/j.issn.1006-5725.2023.19.023
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Objective To investigate the application of high?frequency ultrasound for the diagnosis of diabetic peripheral neuropathy (DPN). Methods A total of 141 diabetic patients were selected and divided into diabetic peripheral neuropathy group (DPN group,n = 44),diabetic group (DM group,n = 56) and non?diabetic group (NDM group,n = 41). The cross?sectional area (CSA) of the sciatic, tibial, common peroneal, posterior tibial and median nerves were measured by high?frequency ultrasound in each group, and the Michigan Neuropathy Screening Instrument (MNSI) and the Toronto Clinical Scoring System (TCSS) were applied to assess peripheral nerve function in patients in the DM and DPN groups. The ROC curves were used to analyze the value of peripheral nerve cross?sectional area (CSA) in the diagnosis of DPN. Results Compared with the NDM and DM groups, the measured sciatic, tibial, and posterior tibial nerve CSA was significantly greater in the DPN group (P < 0.05); he MNSI scores was significantly higher in the DPN group compared with the DM group (P < 0.05), CSA was positively correlated with the MNSI score and TCSS score (P < 0.05);ROC curve analysis showed that the posterior tibial nerve CSA had a significant predictive value in the diagnosis of DPN. Conclusion The CSA of sciatic nerve, tibial nerve, and posterior tibial nerve measured by high?frequency ultrasound was significantly greater in the DPN group compared with the DM and NDM groups. CSA correlated well with MNSI scores and TCSS scores. High?frequency ultrasound?measured CSA of the sciatic, tibial, and posterior tibial nerves has potential value in the diagnosis of DPN.

Reviews
Progress of SphK1/S1P in the biological behavior of tumor malignancy
Wenlu ZHANG,Chunyan. XU
2023, 39(19):  2551-2555.  doi:10.3969/j.issn.1006-5725.2023.19.024
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Sphingophosphokinase 1 (SphK1) is a regulator of sphingomolipin metabolites that catalyzes the conversion of sphingosine-1-phosphate (S1P) to sphingosine-1-phosphate. SphK1/S1P is overexpressed in a variety of cancers. This paper reviewed the role and mechanism of SphK1/S1P in malignant biological behaviors of tumors, such as tumor cell proliferation, epithelial mesenchymal transformation, acquisition of stem-like properties, remodeling of tumor microenvironment, regulation of tumor immune function, and promotion of distant metastasis of tumor cells. It is suggested that SphK1/S1P plays a key role in multiple malignant biological behaviors of tumors.

TCM medicine understanding of tumor microenvironment based on cancer toxicity theory
Danting WEN,Huiping. ZHOU
2023, 39(19):  2556-2560.  doi:10.3969/j.issn.1006-5725.2023.19.025
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As a tumor ecosystem on which tumors grow and develop, tumor microenvironment is the key to tumor occurrence and development. In terms of cancer toxicity theory, the formation and transformation of tumor microenvironment are closely related to different stages of cancer toxicity development. The treatment of tumor microenvironment can be carried out according to the pathological characteristics of different stages of cancer development. Based on the theory of cancer toxicity, this paper explores the TCM understanding of tumor microenvironment by finding out the commonality of development characteristics between cancer toxicity and tumor microenvironment, and provides theoretical basis for TCM treatment of tumor microenvironment.