Application of Clinical Prediction Models for Postoperative Complications of Colorectal Cancer / 肿瘤防治研究

Postoperative complications of colorectal cancer (CRC) are the main cause of postoperative death and seriously affect the quality of life and survival time of patients. The application of a clinical prediction model for postoperative complications of CRC can help promptly identify high-risk patients. Accordingly, reasonable intervention measures can be actively taken to reduce the incidence of postoperative complications of CRC. A scientific basis can also be provided to improve the prognosis of patients. In this work, literature on the risk-factor analysis and prediction-model construction of postoperative complications of CRC at home and abroad in recent years was collected and reviewed. The evaluation content and efficiency of the clinical prediction models in postoperative complications of CRC were summarized. Their advantages and disadvantages were also analyzed. The purpose of this study was to provide a reference for the subsequent optimization of such models and the development of a strong, clinically practical, and universal risk-screening tool for postoperative complications of CRC.

Clinical Efficacy of Qiangxin Decoction Combined with Baduanjin in Treatment of Elderly Patients with Chronic Heart Failure and Weakness / 中国实验方剂学杂志

ObjectiveChronic heart failure （CHF） is the terminal stage of cardiovascular disease. The adverse cardiovascular events of CHF patients with weakness have increased significantly. Traditional Chinese medicine （TCM） has a good effect on CHF. However，there are few reports on the clinical observation of the treatment of CHF with weakness in elderly patients by TCM combined with conventional health-preserving exercises. This study aimed to explore the clinical efficacy of Qiangxin decoction combined with Baduanjin in the treatment of elderly patients with CHF and weakness. MethodSixty CHF patients with Qi deficiency，blood stasis，and water retention syndrome admitted to the Cardiovascular Department of the First Affiliated Hospital of Guangxi University of Chinese Medicine from January 2020 to December 2021 were enrolled. The patients in the control group were treated with conventional western medicine according to the guidelines，while those in the treatment group received additional Qiangxin decoction and Baduanjin exercise based on the therapeutic protocol of the control group. The levels of serum N-terminal B-type brain natriuretic peptide precursor （NT-proBNP），creatine kinase （CK），lactate dehydrogenase （LDH），free fatty acid （FFA），left ventricular ejection fraction （LVEF），left ventricular end-diastolic dimension （LEVDD），6-minute walk distance （6MWD），Minnesota Living with Heart Failure Questionnaire （MLHFQ）， and Tilburg Frailty Indicator （TFI） scores of the two groups were observed before and one month after treatment. At the same time，the re-admission within three months was compared between the two groups. ResultThere was no significant difference between the two groups in terms of the general data and the therapeutic indexes before treatment. After treatment，the NT-proBNP，CK，LDH，FFA，LVEDD，MLHFQ， and TFI scores of the two groups were lower than those before treatment（P<0.05，P<0.01）， and the LVEF and 6MWD were higher（P<0.05，P<0.01）. The efficacy of the treatment group was superior to that of the control group after treatment （P<0.05，P<0.01）. The re-admission rate within three months in the treatment group was 7.1% （2/28）， lower than 30.8% （8/26） in the control group （χ2=4.897，P<0.05）. ConclusionQiangxin decoction combined with Baduanjin is helpful to improve the body energy metabolism，heart function，quality of life，and weakness level of elderly CHF patients with weakness， and reduce the rate of re-admission.

Discrepancy between behavioral-indicated and perceived candidacy for HIV pre-exposure prophylaxis among men who have sex with men in Chengdu, China / 北京大学学报(医学版)

OBJECTIVE@#To explore the discrepancy between behavioral-indicated candidacy and perceived candidacy (behavioral-perceived gap) and its associated factors of human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM), so as to identify the focus population of PrEP interventions and to design and implement targeted interventions.@*METHODS@#We recruited a sample of 622 HIV-negative MSM who were regular clients of a community-based organization located in Chengdu, China, from November to December 2021. A cross-sectional questionnaire was used to collect the participants' information on social demographics, PrEP-related knowledge and cognitions, and risk behaviors. In this study, behaviorally eligible for PrEP was defined as performing at least one type of high-risk behavior in the past six months, including inconsistent condom use, sex with an HIV-positive partner, confirmed sexual transmitted infections (STI) diagnosis, substance use, and post-exposure prophylaxis (PEP) experience. Logistic regression models were fitted, and multivariate analyses were adjusted for social demographics.@*RESULTS@#Among the 622 eligible participants, 52.6% (327/622) were classified as behaviorally eligible for PrEP. Only 37.9% (124/327) of the participants perceived themselves as appropriate candidates for PrEP and 62.1% (203/207) had discrepancy between behavioral-indicated and perceived candidacy. 85.9% (281/327) had heard of PrEP, and 14.2% (40/281) accessed PrEP information through health care providers. Of the 327 participants eligible for behavior-indicated PrEP use, about half (47.1%) knew how to obtain PrEP medication and 33.0% had a professional PrEP counseling experience. The majority (93.3%) had no or few friends using PrEP. 54.1% scored eight or above in PrEP knowledge level. 66.7% reported having two or more sexual partners in the past six months. After adjusting for age and recruitment channel, we found six factors that were associated with perceived candidacy for PrEP, including PEP use [adjusted odds ratio (ORA)=2.20; 95% confidence interval (CI): 1.33-3.63], PrEP availability (ORA=1.69; 95%CI: 1.06-2.68), a greater number of PrEP-using friends (ORA=4.92; 95%CI: 1.77-13.65), PrEP know-ledge (ORA=2.21; 95%CI: 1.38-3.56), multiple sexual partnership (ORA=1.77; 95%CI: 1.07-2.94), and perceiving a higher risk of HIV infection (ORA=4.02; 95%CI: 1.73-9.32). Substance use during sex and PrEP information channel were not statistically associated with this beha-vioral-perceived gap.@*CONCLUSION@#We observed a high discrepancy between behavioral-indicated and perceived candidacy for PrEP among Chengdu MSM in China. Future PrEP implementation efforts should be made in skills training in assessing HIV infection risk, increasing PrEP knowledge, providing professional PrEP counselling, and fostering PrEP support environment.

Association between semen collection time and semen parameters: an observational study / 亚洲男科学杂志(英文版)

The process of semen collection plays a key role in the quality of semen specimens. However, the association between semen collection time and semen quality is still unclear. In this study, ejaculates by masturbation from 746 subfertile men or healthy men who underwent semen analysis were examined. The median (interquartile range) semen collection time for all participants was 7.0 (5.0-11.0) min, and the median time taken for semen collection was lower in healthy men than that in subfertile men (6.0 min vs 7.0 min). An increase in the time required to produce semen samples was associated with poorer semen quality. Among those undergoing assisted reproductive technology (ART), the miscarriage rate was positively correlated with the semen collection time. After adjusting for confounders, the highest quartile (Q4) of collection time was negatively associated with semen volume and sperm concentration. A longer time to produce semen samples (Q3 and Q4) was negatively correlated with progressive and total sperm motility. In addition, there was a significant negative linear association between the semen collection time and the sperm morphology. Higher risks of asthenozoospermia (adjusted odds ratio [OR] = 2.06, 95% confidence interval [CI]: 1.31-3.25, P = 0.002) and teratozoospermia (adjusted OR = 1.98, 95% CI: 1.10-3.55, P = 0.02) were observed in Q3 than those in Q1. Our results indicate that a higher risk of abnormal semen parameter values was associated with an increase in time for semen collection, which may be related to male fertility through its association with semen quality.

Performance evaluation of nucleic acid testing system for blood screening in high-altitude areas / 中国输血杂志

【Objective】 To validate the performance of a nucleic acid testing(NAT) system for blood screening in the high-altitude Nagqu region of Tibet, in order to assess the capability of NAT in high-altitude areas and further enhance blood safety. 【Methods】 Various methods were employed to evaluate the analytical sensitivity, reproducibility, ability to prevent cross-contamination, and comparison between different NAT systems. 【Results】 The NAT system in the Nagqu region of Tibet achieved a 100% detection rate for high-concentration HBV DNA and HIV-1 RNA samples, and over 90% for medium-concentration samples. PROBIT analysis revealed the lower limits of detection (LOD) for HBV DNA and HIV-1 RNA to be 8.29 IU/mL (95% CI, 5.88~20.55 IU/mL) and 40.52 IU/mL (95% CI, 30.26~85.92 IU/mL), respectively. For HCV RNA genotype 2a, the LOD was 97.14 IU/mL (95% CI, 71.00~182.67 IU/mL), all of which were lower than the declared minimum detectable concentrations in the instructions. Reproducibility analysis demonstrated a 100% level of consistency within the system. Cross-contamination performance verification showed a strong ability to resist cross-contamination. Comparative analysis of repeated testing of low-concentration HBV DNA samples and multi-system testing in plain areas revealed consistency rates of 77.78%(14/18) and 77.27%(17/22), respectively, indicating certain differences between the NAT system in Nagqu region and other systems. 【Conclusion】 The NAT system exhibited excellent performance in blood screening at high altitudes. The results of performance validation in high-altitude blood screening NAT systems were largely consistent with those in plain areas, providing a reliable basis for enhancing blood safety in high-altitude regions.

Protective effect of chrysin regulates AMPK-NLRP3 signaling mediated pyroptosis to alleviate hepatic fibrosis / 药学学报

This study investigated the protective effect of chrysin on hepatic fibrosis by regulating AMP-activated kinase (AMPK)-NOD-like receptor protein 3 (NLRP3) mediated pyroptosis pathway. The hepatic fibrosis model of mice was established by thioacetamide (TAA) in vivo. Except the control and chrysin alone groups, the mice were injected intraperitoneally with TAA at 100 mg·kg-1, three times per week for the first week. From the 2nd to 5th week, mice were injected intraperitoneally with TAA at 200 mg·kg-1, three times per week for the next 4 weeks. Chrysin groups were intragastrically administrated once per day to 5th week. The histopathological changes were detected by HE and Masson staining. The levels of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were assessed by the kits. All animal experiments were approved by the Medical Ethics Committee of Affiliated Zhongshan Hospital of Dalian University (DWLL2019060). LX-2 cells were stimulated by (transforming growth factor-β, TGF-β) in vitro. The protein expressions of AMPKα, p-AMPKα, NLRP3, cysteinyl aspartate specific proteinase-1 (caspase-1), gasdermin D (GSDMD) were detected by Western blot, and the mRNA levels of collagen-Ι, α-smooth muscle actin (α-SMA), interleukin-1β (IL-1β), IL-18, caspase-1, GSDMD were analysis by reverse transcription-polymerase chain reaction (RT-PCR). Chrysin attenuated the increases in serum AST and ALT levels in the TAA group, while significantly improved the changes of liver morphology, reduced liver tissue inflammatory cell infiltration and inhibited collagens deposition. Compared with TAA group, chrysin effectively activated AMPKα phosphorylation and inhibited hepatic NLRP3 inflammasome activation. Additionally, the protein expressions and mRNA levels of IL-1β, IL-18, caspase-1 and GSDMD in chrysin groups were decreased. Chrysin inhibited the expressions of collagen-Ι and α-SMA, enhanced the phosphorylation of AMPKα, and decreased the expressions of NLRP3 and GSDMD. Therefore, chrysin may inhibit inflammatory injury and pyroptosis possibly by activating AMPK and inhibiting NLRP3 inflammasome to alleviate hepatic fibrosis.

Role of liquid biopsy in early screening and curative effect monitoring and prognosis of gastric cancer / 国际外科学杂志

Gastric cancer is a common cancer in digestive system in China. It′s in the forefront of cancer in terms of morbidity and case fatality, posing a great threat to people′s health. With the advent of the era of precision medicine, the treatment of each patient with gastric cancer must follow the principle of individualization. However, individualized treatment is based on the development of biomarkers. Liquid biopsy has been reported to be a biomarker capable of detecting information about tumorigenesis and progression, and has been suggested as a useful tool for personalized treatment. Compared with traditional "tissue biopsy" , liquid biopsy has significant advantages because it is noninvasive and painless, reduces cost and time for diagnosis, and could be used for diagnosis, prognosis, prediction of disease progression, or as a surrogate marker of response to treatment.For this purpose, the author will review the related detection techniques of liquid biopsy and its role in early screening, efficacy evaluation and recurrence monitoring of gastric cancer.

Analysis of the efficacy of a modified posteromedial approach for Klammer III posterior Pilon fractures / 中华创伤杂志(英文版)

PURPOSE@#To analyze the curative effect and technical points of a modified posteromedial approach in the treatment of Klammer III posterior Pilon fracture.@*METHODS@#A retrospective analysis of patients with Klammer III posterior Pilon fractures were conducted in our department from January 2018 to December 2019. Before the surgery, the patients were fully relieved of swelling and pain, and a comprehensive examination was carried out. The posteromedial approach exposed the posterior and medial fracture block of the distal tibia. According to the fracture of external malleolus, it is determined whether to combine a lateral incision and protect tendons and vascular nerves by a retractor, and then perform a fracture reduction and internal fixation. Postoperatively, the patients were treated with analgesia, detumescence, anticoagulation and rehabilitation exercise. The American orthopaedic foot and ankle society (AOFAS) score and visual analogue score were recorded at regular follow-up after surgery. A t-test was used for the comparison of the preoperative and final AOFAS score.@*RESULTS@#There were 7 male and 13 female (n = 20) included in the study, aged 22 to 88 years (average age 54.2 years). The injury mechanisms were falling from a height (n = 7), traffic accident (n = 6), walking injury (n = 2) and heavy injury (n = 5). The postoperative follow-up duration was 12-24 months (mean 16.95 months). The AOFAS score of the 20 patients before and after surgery were compared. The preoperative AOFAS score was 38.90 ± 3.91, and the final AOFAS score was 80.55 ± 4.20, (p < 0.001). The mean final visual analogue scores at rest, active and weight-bearing walking were 0.30, 0.85 and 1.70, respectively. One patient reported poor postoperative wound healing and required a return to hospital for debridement and anti-infection treatment.@*CONCLUSION@#In the treatment of Klammer III posterior Pilon fractures, the modified posteromedial approach can fully expose the fracture block and the collapsed articular surface of the medial malleolus, achieve good reduction and internal fixation with limited injury of the tendon and vascular nerves, and have a better prognosis.

Right upper lobe resection assisted by Toumai® endoscopic surgery robot in two patients / 中国胸心血管外科临床杂志

@#Objective    To analyze the efficacy and safety of Toumai® endoscopic surgery robot in right upper lobe resection. Methods    The clinical data of 2 patients with non-small cell lung cancer who received right upper lobe resection with Toumai® endoscopic surgery robot in Shanghai Chest Hospital, Shanghai Jiao Tong University in November 2021 were retrospectively analyzed. Both patients were male, aged 66 years and 44 years, respectively. Results    The operation was successful in both patients with no conversion to thoracotomy, surgical complication or death. The operation time was 65 min and 48 min, and the amount of intraoperative bleeding was 80 mL and 50 mL, respectively. The postoperative hospital stay was 3 days. There was no blood transfusion during the perioperative period. Conclusion    The application of Toumai® endoscopic surgery robot in lobectomy is preliminarily proved to be safe and effective. Compared with Da Vinci robotic surgery system, it has similar clear 3D vision and flexible and stable operation, which can become one of the important choices for the new generation of minimally invasive chest surgery.

Patient factors influencing preoperative expectations of patients undergoing total knee arthroplasty / 北京大学学报(医学版)

OBJECTIVE@#To investigate the expectations of patients for total knee arthroplasty (TKA), and to analyze its influencing factors.@*METHODS@#Experimental design: Single center, retrospective, multiple regression analysis. The data including the age, height, and weight of 108 patients undergoing unilateral TKA due to end-stage osteoarthritis were obtained. The patients' preoperative Hospital for Special Surgery (HSS) knee arthroplasty expectation score, the Western Ontario and McMaster Universities (WOMAC) score, Knee Society score (KSS), the MOS 36-item short-from health survey (SF-36) score, and visual analogue scale (VAS) were evaluated, and the 30-second chair-stand test (30-CST), 40-meter fast-paced walk test (40-FPWT), 12-level stair-climb test (12-SCT), 3-meter timed up-and-go test (TUG), 6-minute walk test (6-MWT), and recorded daily steps for 7 consecutive days were performed. The SPSS 22.0 software was used for statistical analysis. The observed values of various data were described. Pearson correlation analysis was used to evaluate the correlation between various parameters, and the multi-factor linear regression analysis was used to investigate the influencing factors of the patients preoperative expectation scores.@*RESULTS@#The average expectation score of this group of patients was 58.98±5.44. In the Pearson correlation analysis, the patient's preoperative expectation had a weak correlation to the result of the patient's 12-SCT, TUG, 6-MWT, KSS function score, and SF-36 mental component score (correlation coefficient 0.1-0.3). The patient's preoperative expectation had a moderate correlation to the patient's daily average steps, 30-CST, 40-FPWT, KSS, WOMAC and its pain, stiffness, function scores, SF-36 physical functioning, role-physical, bodily pain, vitality, and physical component score (correlation coefficient 0.3-0.6). In the multivariate linear regression analysis, only the results of 30-CST and the role-physical, bodily pain and vitality in the SF-36 scale were related to the patient's expectation score (P < 0.05).@*CONCLUSION@#The estimated expectation score of patients before TKA is not high. Patients with more severe preoperative pain, worse physical function, and lower overall health are more eager to improve after surgery. Thus surgeons must communicate fully with patients with unrealistic expectations before surgery in order to obtain more satisfactory results postoperatively.

Clinical evaluation of endoscopic super-hemorrhoidal banding for 112 cases of internal hemorrhoids with prolapse (with video) / 中华消化内镜杂志

Objective:To evaluate the safety and efficacy of endoscopic super-hemorrhoidal banding (SHB) in the treatment of internal hemorrhoids with prolapse.Methods:From June 2019 to June 2020, a total of 112 patients with grade Ⅱ and Ⅲ internal hemorrhoids underwent endoscopic SHB at People′s Hospital of Qiandongnan Miao and Dong Autonomous Prefecture. The efficacy of SHB, intraoperative and postoperative complications associated with the operation and patients′ satisfaction were prospectively studied. The follow-up time was over six months.Results:A total of 112 patients received SHB for internal hemorrhoids, 74 patients (66.1%) with grade Ⅱ hemorrhoids and 38 patients (33.9%) with grade Ⅲ hemorrhoids. The operations were successfully performed in all patients. No anal pain or bleeding was reported during the operation. All patients experienced various degrees of anal bulge after the operation, which lasted for 2-24 hours before spontaneous disappearance. Five patients with grade Ⅲ internal hemorrhoids showed dysuria, which was relieved with local heat on the bladder. One patient with grade Ⅲ internal hemorrhoid had bloody stool on day 14. The bleeding was stopped with another banding at the site of bleeding ulcer. All patients completed the follow-up. No complications such as bleeding, pain, infection or stenosis occurred in one month after operation. Eighteen patients with grade Ⅲ had partial prolapse after operation without bleeding or other symptoms. Six of them received additional SHB treatment and prolapse disappeared. No postoperative complications occurred in the six months of follow-up in all patients. The satisfaction rate was 100.0% according to the survey.Conclusion:Endoscopic SHB is an effective, safe and simple technique for internal hemorrhoids with prolapse.

Quality evaluation of compound Chinese medicines as related to clinical efficacy / 药学学报

The quality evaluation of compound Chinese medicines is an important but challenging issue in this research field, which has been paid much controversial due to the constrained association with clinical efficacy. Developing a methodology for quality evaluation of compound Chinese medicines related to clinical efficacy is an important measure in research on Chinese material medica quality to ensure clinical effectiveness and safety. Therefore, based on the research concept that "originating from clinic-testing in experiment-returning to clinic", and taking Xiaoke prescription as an example, the characteristic information of metabolome, proteome and microbiome are discussed from the clinical aspect, and the integrated markers associated with clinical efficacy constructed with artificial intelligence technology. Taking the integrated markers as the link and indication are connecting the clinical and basic, the main pharmacodynamic substances and key targets of Xiaoke prescription that are related to clinical efficacy are explained. Clinical samples are used for validation. Based on the main pharmacodynamic substances and key targets, methods and key technologies for chemical and biological evaluation of the quality of Xiaoke prescription are established, providing a methodology for quality evaluation of compound Chinese medicines, including clinical efficacy response indicators (related to clinic), main pharmacodynamic substances (chemical evaluation), and key targets (biological evaluation), to provide new ideas and methods for improving the quality evaluation of compound Chinese medicines.

Study on Mechanism of Quercetin in Heart Failure Based on Network Pharmacology and Experimental Validation / 中国实验方剂学杂志

Objective:To predict the therapeutic targets and related signaling pathways of quercetin in the treatment of heart failure （HF） by network pharmacology and molecular docking methods，and further clarify its mechanisms through <italic>in vitro</italic> cell model. Method:The pharmacological targets of quercetin were obtained by SwissTargetPrediction and Targetnet databases； the heart failure related targets were obtained by Online Mendelian Inheritance in Man（OMIM），GeneCards and Therapeutic Target Database（TTD） databases； the protein-protein interaction（PPI） network was analyzed by STRING database（Search Tool for Recurring Instances of Neighbouring Genes），and the PPI network diagram of quercetin for heart failure target was established. Cytoscape 3.7.2 software was used for analyzing and screening the anti-heart failure network nodes of quercetin，and the obtained targets were enriched with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analysis by DAVID database. In order to explore the mechanism of quercetin in the treatment of heart failure，we used cell model to verify the function in heart failure treatment. Results:The predicted results showed that there were 23 targets for the treatment of heart failure，such as Matrix Metallopeptidase-9（MMP-9），androgen receptor（AR），coagulation factor 2（F2），insulin like growth factor 1 receptor（IGF1R），epidermal growth factor receptor（EGFR），janus kinase-2（JAK2），cytochrome P450 family 19 subfamily A member 1（CYP19A1），estrogen receptor-1（ESR1），tumor necrosis factor（TNF），protein tyrosine phosphatase receptor type C（PTPRC） and cytochrome P450 family 17 subfamily A member 1（CYP17A1） etc. The results suggest that quercetin may play a role in the treatment of heart failure by intervening in the physiological processes of cardiovascular cell proliferation and metabolism，regulating hypoxia-inducible factor 1 （HIF-1）signaling pathway and steroid hormone biosynthesis. Conclusion:Quercetin has the characteristics of multi-target，multi-channel and multi-channel in the treatment of heart failure. It may play a role in the treatment of heart failure by regulating MMP-9，EGFR and other key genes，participating in the biological process of cardiac and vascular cell proliferation and metabolism.

Analysis of surgical strategy of percutaneous endoscopic lumbar discectomy in young and middle-aged double-segment patients with lumbar disc herniation / 北京大学学报(医学版)

OBJECTIVE@#To investigate clinical efficacy and safety of single and double segmental percutaneous lumbar discectomy for young and middle-aged patients with double-segment disc herniation.@*METHODS@#Retrospective analysis was undertaken for 32 young and middle-aged patients with percutaneous endoscopic lumbar discectomy (PELD) in the treatment of double-segment lumbar disc herniation from January 2015 to October 2018 in Peking University First Hospital. In the study, 18 cases were treated with single-segment treatment and 14 cases with double-segment treatment. Visual analogue score (VAS) and oswestry disability index (ODI) assessment were used to compare clinical symptom outcomes before surgery, 3 months after surgery and at the last follow-up. Macnab criteria were used to assess the patients' overall satisfaction after surgery. Imaging parameters included lumbar lordosis, intervertebral height at each segment and endplate angle of lesion segment on the X-ray. And Michigan State University(MSU) rating and Pfirrmann scoring system were used to evaluate the grade of disc herniation and disc degeneration respectively on magnetic resonance imaging (MRI). The perioperative parameters included the surgeon, anesthesia method, operation time, postoperative hospital stay, postoperative bracing time and perioperative complications.@*RESULTS@#The mean follow-up time was (26.78±10.64) months. There was no significant difference in the follow-up time and baseline information between the two groups(P > 0.05). ODI scores 3 months post-operatively and at the last follow-up were lower in the double segment (P < 0.05). The ODI improvement was also more significant in the double-segment group at the last follow-up (P < 0.05). There was no significant difference in radiographic parameters at baseline (P>0.05). MSU scale for the primary segment was significantly lowered after both operations (P < 0.05). MSU scale for secondary segment was significantly lowered in double segment group but not in single segment group. Other imaging parameters were similar between the two groups (P > 0.05). The operation time of the single-segment group was significantly shorter than that of the double-segment group(P < 0.001). No perioperative complications were found in either group, but three patients underwent secondary lumbar surgery during the postoperative follow-up period in the single-segment group.@*CONCLUSION@#For young and middle-aged patients with double-segment disc herniation, this study suggests double-segment PELD may be more advantageous than single-segment PELD in terms of asuring clinical efficacy without increasing perioperative risks.

Profiling of HAT1-mediated Lysine Acetylation Modification in Liver Cancer / 中国生物化学与分子生物学报

Lysine acetylation has emerged as one of the most important post-translational modifications that participates in various biological and pathological processes. Histone acetyltransferase 1 (HAT1) as the first identified protein ε-amino lysine acetyltransferase is able to regulate the acetylation of histones and non-histone proteins. However‚ the acetylation substrates and sites mediated by HAT1 in liver cancer are poorly understood. In this study‚ we demonstrated that HAT1 was highly expressed in the liver cancer tissues‚ which was negatively associated with the prognosis of patients. Based on the establishment of the HAT1-knockout HepG2 cell line‚ we employed a quantitative proteomics approach to study the profiling of acetylation mediated by HAT1 in HepG2 cells. Interestingly‚ we identified a total of 858 Kac sites on 547 proteins in the HepG2 cell line‚ in which HAT1 mediated the levels of Kac of 74 sites on 68 proteins. The pathways and metabolic processes that were affected by HAT1-dependent acetylation modification were analyzed by bioinformatics. The results show that Kac regulates disease development‚ RNA biology‚ spliceosome and nucleosome assembly‚ oxidative stress‚ various signaling pathways and metabolic pathways‚ etc.. Moreover‚ we verified that the HAT1-mediated acetylation modification could promote abnormal lipid metabolism. CCK8 assays‚ clone formation and Edu assays revealed that HAT1 could remarkably enhance the cell proliferation of liver cancer in vitro. Thus‚ our finding explored the profiling of HAT1-mediated protein acetylation in HepG2 cells‚ which provides new insights into the underlying mechanism by which HAT1 mediates the development of liver cancer. Clinically‚ the HAT1-mediated acetylation sites could be used for the precise targets of drug development.

PCNA Confers the Conversion of Hepatitis B Virus Relaxed Circular DNA to Covalently Closed Circular DNA by Its DNA Binding Domain / 中国生物化学与分子生物学报

Chronic hepatitis B virus (HBV) infection is a primary cause for liver cancer. And the main challenge of curing hepatitis B is the elimination of the stable covalently closed circular DNA (cccDNA) of the viral genome. The formation of HBV cccDNA requires the filling of single-stranded region and the ligation of nicks in relaxed circular DNA (rcDNA) strands. Previously, our group reported that proliferating cell nuclear antigen (PCNA) was involved in the formation of HBV cccDNA. However, the underlying mechanism of the conversion of HBV rcDNA to cccDNA is poorly understood. In the present study, we aim to explore the mechanism by which PCNA contributes to the conversion of HBV rcDNA to cccDNA. Our data showed that PCNA was involved in the process of HBV rcDNA repair. The knockout of PCNA by the CRISPR/Cas9 system remarkably blocked the conversion of HBV rcDNA to cccDNA, while the ectopic expression of PCNA could effectively rescue the event (P<0. 001). Knockout of PCNA significantly slowed down the conversion kinetics of HBV rcDNA to cccDNA (P<0. 01). Mechanically, the DNA binding domain of PCNA was required for the process of HBV rcDNA repair to cccDNA (P<0. 01). Thus, we conclude that PCNA confers the conversion of HBV rcDNA to cccDNA by its DNA binding domain. Clinically, PCNA might serve as a novel target for antiviral therapy.

Iron deficiency and early childhood caries: a systematic review and meta-analysis / 中华医学杂志(英文版)

BACKGROUNDS@#Previous surveys have found that children with iron deficiency (ID) were likely to suffer from early childhood caries (ECC). We aimed to assess the scientific evidence about whether ID is intrinsically related to ECC.@*METHODS@#The medical subject headings (MeSH) terms and free words were searched on PubMed, Web of Science, Cochrane, China National Knowledge Infrastructure, Wanfang, and the Database for Chinese Technical Periodicals from March 2020 to September 2020. Two researchers independently screened the articles. Data extraction and cross-checking were performed for the studies that met the inclusion criteria. Meta-analysis was performed using the Cochrane Collaboration's Review Manager 5.3 software.@*RESULTS@#After excluding duplication and irrelevant literature, 12 case-control studies were included in the study. The meta-analysis demonstrated that children with ECC were more likely to have ID (odds ratio [OR] = 2.63, 95% confidence interval [CI]: [1.85, 3.73], P < 0.001). There was no statistically significant association found between the level of serum ferritin and ECC (weighted mean difference (WMD) = -5.80, 95% CI: [-11.97, 0.37], P = 0.07). Children with ECC were more likely to have iron-deficiency anemia (OR = 2.74, 95% CI: [2.41,3.11], P < 0.001). The hemoglobin (HGB) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -9.96, 95% CI: [-15.45, -4.46], P = 0.0004). The mean corpuscular volume (MCV) levels in the ECC group were significantly lower compared with that in the ECC-free group (WMD = -3.72, 95% CI: [-6.65, -0.79], P = 0.01).@*CONCLUSIONS@#ID was more prevalent in children with ECC, and the markers of iron status in the ECC group, such as serum ferritin, HGB, and MCV, were relatively lower than the ECC-free group.

Exploration on rationality evaluation approach of drug combination medication based on sequential analysis and machine learning / 中国中药杂志

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.

Apical ectodermal ridge regulates three principal axes of the developing limb / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Understanding limb development not only gives insights into the outgrowth and differentiation of the limb, but also has clinical relevance. Limb development begins with two paired limb buds (forelimb and hindlimb buds), which are initially undifferentiated mesenchymal cells tipped with a thickening of the ectoderm, termed the apical ectodermal ridge (AER). As a transitional embryonic structure, the AER undergoes four stages and contributes to multiple axes of limb development through the coordination of signalling centres, feedback loops, and other cell activities by secretory signalling and the activation of gene expression. Within the scope of proximodistal patterning, it is understood that while fibroblast growth factors (FGFs) function sequentially over time as primary components of the AER signalling process, there is still no consensus on models that would explain proximodistal patterning itself. In anteroposterior patterning, the AER has a dual-direction regulation by which it promotes the sonic hedgehog (Shh) gene expression in the zone of polarizing activity (ZPA) for proliferation, and inhibits Shh expression in the anterior mesenchyme. In dorsoventral patterning, the AER activates Engrailed-1 (En1) expression, and thus represses Wnt family member 7a (Wnt7a) expression in the ventral ectoderm by the expression of Fgfs, Sp6/8, and bone morphogenetic protein (Bmp) genes. The AER also plays a vital role in shaping the individual digits, since levels of Fgf4/8 and Bmps expressed in the AER affect digit patterning by controlling apoptosis. In summary, the knowledge of crosstalk within AER among the three main axes is essential to understand limb growth and pattern formation, as the development of its areas proceeds simultaneously.

BRCA1/2 mutation status in patients with metachronous breast and ovarian malignancies: clues towards the implementation of genetic counseling / 부인종양

Objective@#The characteristics of patients with metachronous breast and ovarian malignancies and the pathogenic role of BRCA1/2 mutations remain poorly understood. We investigated these issues through a review of hospital records and nationwide Taiwanese registry data, followed by BRCA1/2 mutation analysis in hospital-based cases. @*Methods@#We retrospectively retrieved consecutive clinical records of Taiwanese patients who presented with these malignancies to our hospital between 2001 and 2017. We also collected information from the Data Science Center of the Taiwan Cancer Registry (TCR) between 2007 and 2015. Next-generation sequencing and multiplex ligation-dependent probe amplification were used to identify BRCA1/2 mutations and large genomic rearrangements, respectively. When BRCA1/2 mutations were identified in index cases, pedigrees were reconstructed and genetic testing was offered to family members. @*Results@#A total of 12,769 patients with breast cancer and 1,537 with ovarian cancer were retrieved from our hospital records. Of them, 28 had metachronous breast and ovarian malignancies. We also identified 113 cases from the TCR dataset. Eighteen hospital-based cases underwent BRCA1/2 sequencing and germline pathogenic mutations were detected in 7 patients (38.9%, 5 in BRCA1 and 2 in BRCA2). All BRCA1/2 mutation carriers had ovarian high-grade serous carcinomas. Of the 12 patients who were alive at the time of analysis, 5 were BRCA1/2 mutation carriers. All of them had family members with BRCA1/2-associated malignancies. @*Conclusions@#Our results provide pilot evidence that BRCA1/2 mutations are common in Taiwanese patients with metachronous breast and ovarian malignancies, supporting the clinical utility of genetic counseling.