OBJECTIVE To establish an HPLC method for determination of the related substances in papaverine hydrochloride. METHODS NanoChrom ChromCore 120 C8 column was used; the mobile phase A consisted of 3.4 g·L−1 potassium dihydrogen phosphate aqueous solution, adjust pH to 3.5 with phosphoric acid-acetonitrile(90∶10), the mobile phase B was methanol, with gradient elution at the flow rate of 0.8 mL·min−1; the detection wavelength was 238 nm; the column temperature was 50 ℃. RESULTS The minimum separation between the main component and each impurity was >1.5; Papaverine and its thirteen impurities showed a good linear relationship in the self-concentration range(r>0.999); and the average recoveries were 93.1%−101.2% with RSDs of 2.3%−8.1%. CONCLUSION The method is accurate, sensitive and reliable, which is suitable for the determination of related substances in papaverine hydrochloride.

Objective:To explore the association between polymorphisms of transforming growth factor-β(TGF-β)signaling pathway and non-syndromic cleft lip with or without cleft palate(NSCL/P)among Asian populations,while considering gene-gene interaction and gene-environment interaction.Methods:A total of 1 038 Asian NSCL/P case-parent trios were ascertained from an international consortium,which conducted a genome-wide association study using a case-parent trio design to investigate the genes affec-ting risk to NSCL/P.After stringent quality control measures,343 single nucleotide polymorphism(SNP)spanning across 10 pivotal genes in the TGF-β signaling pathway were selected from the original genome-wide association study(GWAS)dataset for further analysis.The transmission disequilibrium test(TDT)was used to test for SNP effects.The conditional Logistic regression models were used to test for gene-gene interaction and gene-environment interaction.Environmental factors collected for the study in-cluded smoking during pregnancy,passive smoking during pregnancy,alcohol intake during pregnancy,and vitamin use during pregnancy.Due to the low rates of exposure to smoking during pregnancy and al-cohol consumption during pregnancy(＜3％),only the interaction between maternal smoking during pregnancy and multivitamin supplementation during pregnancy was analyzed.The threshold for statistical significance was rigorously set at P=1.46 × 10-4,applying Bonferroni correction to account for multiple testing.Results:A total of 23 SNPs in 4 genes yielded nominal association with NSCL/P(P＜0.05),but none of these associations was statistically significant after Bonferroni's multiple test correction.How-ever,there were 6 pairs of SNPs rs4939874(SMAD2)and rs1864615(TGFBR2),rs2796813(TGFB2)and rs2132298(TGFBR2),rs4147358(SMAD3)and rs1346907(TGFBR2),rs4939874(SMAD2)and rs1019855(TGFBR2),rs4939874(SMAD2)and rs12490466(TGFBR2),rs2009112(TGFB2)and rs4075748(TGFBR2)showed statistically significant SNP-SNP interaction(P＜1.46 × 10-4).In contrast,the analysis of gene-environment interactions did not yield any significant results after being cor-rected by multiple testing.Conclusion:The comprehensive evaluation of SNP associations and interac-tions within the TGF-β signaling pathway did not yield any direct associations with NSCL/P risk in Asian populations.However,the significant gene-gene interactions identified suggest that the genetic architec-ture influencing NSCL/P risk may involve interactions between genes within the TGF-β signaling path-way.These findings underscore the necessity for further investigations to unravel these results and further explore the underlying biological mechanisms.

Objective:To investigate the feasibility of a three-dimensional no new U-Net (3D nnU-Net) deep learning (DL) network for the automatic segmentation of colorectal cancer (CRC) based on abdominal CT images.Methods:This was a cross-sectional study. From January 2018 to May 2023, a total of 2180 primary CRC patients, confirmed by pathology at the Guangdong Provincial Hospital of Traditional Chinese Medicine (center 1, n=777), Nanfang Hospital, Southern Medical University (center 2, n=732), and Sun Yat-sen Memorial Hospital (center 3, n=671), were enrolled in this retrospective study. The baseline abdominal CT examination of each patient was conducted using CT equipment from 7 different models across 4 vendors, at the 3 centers, encompassing both the arterial phase (AP) and venous phase (VP). Two radiologists manually delineated the volume of interest to circumscribe the entire tumors in dual-enhanced phase CT images. The CT data of CRC patients from center 1 and center 3 were merged and divided into a training set ( n=1 159) and a validation set ( n=289) using a weighted random method with a ratio of 4∶1. The patients from center 2 were used as an independent external test set ( n=732). The 3D nnU-Net segmentation model was trained and tested. Using manually annotated label data as the benchmark, segmentation performance of the model was evaluated based on different phases and tumor locations. The segmentation coverage rate (SCR), Dice similarity coefficient (DSC), recall (REC), precision (PRE), F1-score, and 95% Hausdorff distance (HD 95) were calculated. The mean manual segmentation time and the mean automatic time were compared using independent samples t-test. Results:In the independent external test set, the performance of the 3D nnU-Net model based on the AP CT images was superior to that based on the VP CT images. On the AP images, the SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.865, 0.714, 0.716, 0.736, 0.714, and 27.228, respectively; on the VP images, they were 0.834, 0.679, 0.710, 0.675, 0.679, and 29.358, respectively. The model achieved the best performance on right-sided colon cancer, with SCR, DSC, REC, PRE, F1-score, and HD95 on the AP CT images at 0.901, 0.775, 0.780, 0.787, 0.775, and 21.793, respectively. Next were left-sided colon cancer and rectal cancer, while the segmentation performance for transverse colon cancer was the worst (SCR, DSC, REC, PRE, F1-score, and HD 95 were 0.731, 0.631, 0.641, 0.630, 0.631 and 38.721, respectively). The automatic segmentation time on a single phase was (1.0±0.3) min, while the manual segmentation time was (17.5±6.0) min ( t=128.24, P<0.001). Conclusions:After training and validating on a dataset from multiple centers with various CT scanner vendors, the 3D nnU-Net DL model demonstrates the capability to automatically segment CRC based on abdominal CT images, while also showcasing commendable robustness and generalization ability.

Objective:To investigate the safety of minimally invasive liver resection for resectable hepatocellular carcinoma (HCC) complicated with portal hypertension.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopathological data of 807 patients with resectable HCC who underwent minimally invasive liver resection in 8 medical centers, including Sir Run Run Shaw Hospital, Affiliated with the Zhejiang University School of Medicine et al, from June 2011 to November 2022 were collected. There were 670 males and 137 females, aged 58(50,66)years. Of the 807 patients, 173 cases with portal hypertension were divided into the portal hypertension group, and 634 cases without portal hypertension were divided into the non-portal hypertension group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and post-operative situations; (3) subgroup analysis. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.001. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was constructed using the non-parameter rank sun test. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 807 patients, 268 cases were successfully matched, including 134 cases in the portal hypertension group and 134 cases in the non-portal hypertension group. The elimination of the tumor diameter and robot-assisted surgery confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. The occlusion time of porta hepatis, cases with intraoperative blood transfusion, cases with postoperative complication, cases with complication >Ⅱ grade of Clavien-Dindo classification, cases of Clavien-Dindo classification as Ⅰ grade, Ⅱ grade, Ⅲ grade, Ⅳ grade, cases with liver related complication were 27.0(15.0,43.0)minutes, 33, 55, 15, 13, 29, 14, 1, 37 in the portal hypertension group, versus 35.0(22.0,60.0)minutes, 17, 25, 5, 14, 9, 4, 1, 13 in the non-portal hypertension group, showing significant differences in the above indicators between the two groups ( Z=-2.15, χ2=6.30, 16.39, 4.38, 20.72, 14.16, P<0.05). (3) Subgroup analysis. Results of subgroups analysis showed that in cases with major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 243.5(174.6,296.3)minutes, 200.0(150.0,600.0)mL, 7.5(6.0,13.0)days in the portal hypertension group, versus 270.0(180.0,314.5)minutes, 200.0 (75.0,450.0)mL, 7.0(5.5,10.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.54, -1.73, -0.92, P>0.05). In cases with non-major live resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 8.0(5.0,10.0)days in the portal hypertension group, versus 170.0(120.0,227.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.5,9.0)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-1.39, -0.10, 1.05, P>0.05). In cases with anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 210.0(150.0,285.0)minutes, 150.0(50.0,200.0)mL, 8.0(6.0,9.3)days in the portal hypertension group, versus 225.5(146.3,306.8)minutes, 100.0(50.0,250.0)mL, 7.0(6.0,9.0)days in the non-portal hypertension group, showing no significant difference in the above indica-tors between the two groups ( Z=-0.75, -0.26, -0.91, P>0.05). In cases with non-anatomical liver resection, the operation time, volume of intraoperative blood loss, duration of postoperative hospital stay were 173.5(120.0,231.5)minutes, 175.0(50.0,300.0)mL, 7.0(5.0,11.0)days in the portal hyper-tension group, versus 186.0(123.0,262.5)minutes, 100.0(50.0,200.0)mL, 7.0(5.0,9.5)days in the non-portal hypertension group, showing no significant difference in the above indicators between the two groups ( Z=-0.97, -1.12, -0.98, P>0.05). Conclusion:Minimally invasive liver resection or even major liver resection is safe and feasible for screened HCC patients complicated with portal hyper-tension, but attention should be paid to the prevention and treatment of postoperative complications.

Minute pulmonary meningothelial-like nodules (MPMNs) are benign small lesions in the lungs, with similar pathological characteristics to the meningeal epithelium. MPMNs have similar imaging manifestations to malignant tumors, which can lead to misdiagnosis in clinical practice. There is no consensus on the pathogenesis of MPMNs, with some suggest that MPMNs derive from reactive proliferation, while others suggest that MPMNs share a common origin and molecular mechanism with meningiomas in the central nervous system. Understanding the characteristics of MPMNs and studying their pathogenesis will help improve the understanding and diagnosis of MPMNs. In this article, we reviewed the clinical, pathological, imaging characteristics, differential diagnosis and pathogenesis of MPMNs. We also analyze the existing research advances regarding the pathogenesis and propose prospects for further research.
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Objective:To investigate the effects of compression treatment on occurrence of venous thromboembolism (VTE) after tension-free inguinal hernia repair.Methods:The retrospective cohort study was conducted. The clinical data of 13 263 patients with inguinal hernia who were admitted to 58 medical centers from January to December in 2017 were collected, including 1 668 in Beijing Chaoyang Hospital of Capital Medical University, 782 in East Hospital Affiliated to Tongji University, 558 in Huadong Hospital of Fudan University, 525 in Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, 488 in Ruijin Hospital of Shanghai Jiaotong University School of Medicine, 382 in Tianjin People's Hospital, 378 in Peking University Third Hospital, 364 in Beijing Hospital, 356 in Shengjing Hospital of China Medical University, 348 in Huashan Hospital of Fudan University, 348 in Sichuan Provincial People's Hospital, 328 in Affiliated Hospital of Zunyi Medical University, 304 in Beijing Luhe Hospital of Capital Medical University, 296 in People's Hospital of Changshou District in Chongqing, 290 in Anhui Provincial Hospital, 281 in the First Affiliated Hospital of Dalian Medical University, 281 in Xinjiang Uygur Autonomous People's Hospital, 247 in Qilu Hospital of Shandong University, 220 in Wuhan NO.1 Hospital, 214 in the First Hospital of China Medical University, 213 in West China Hospital of Sichuan University, 206 in the Second Affiliated Hospital of Chongqing Medical University, 202 in Taiyuan Central Hospital of Shanxi Medical University, 197 in the First Affiliated Hospital of Wenzhou University, 191 in Zhongda Hospital of Southeast University, 190 in Tianjin Medical University General Hospital, 189 in Xuzhou Central Hospital, 188 in the First Affiliated Hospital of Harbin Medical University, 187 in the Second Hospital Affiliated to Naval Medical University, 175 in Chengdu Fifth People's Hospital, 173 in Tianjin Nankai Hospital, 172 in the Fourth Affiliated Hospital of China Medical University, 172 in Zhangjiakou First Hospital, 161 in Henan Provincial People's Hospital, 153 in the First Affiliated Hospital of Xi'an Jiaotong University, 149 in Shandong Provincial Hospital, 142 in the Second Hospital of Shandong University, 137 in the First Affiliated Hospital of Hunan University of Medicine, 136 in the Fourth Hospital of Harbin Medical University, 127 in Pingjiang District of the First Affiliated Hospital of Soochow University, 102 in the Central Hospital of Wuhan, 100 in the First Affiliated Hospital of Soochow University, 98 in Peking Union Medical College Hospital of Chinese Academy of Medical Sciences, 97 in the First Affiliated Hospital of Chongqing Medical University, 96 in Xijing Hospital Affiliated to Air Force Medical University, 90 in the Fourth Medical Center of Chinese PLA General Hospital, 81 in Hunan Provincial Hospital of Traditional Medicine, 80 in the First Hospital of Tsinghua University, 80 in Xinhua Hospital of Hubei Province, 61 in the First Affiliated Hospital of Zhengzhou University, 57 in Peking University International Hospital, 50 in Peking University First Hospital, 39 in Zhongnan Hospital of Wuhan University, 38 in Jilin Yan'an Hospital, 37 in China-Japan Union Hospital of Jilin University, 20 in Taikang Xianlin Drum Hospital, 16 in Chinese PLA General Hospital, 3 in the First Affiliated Hospital of Fujian Medical University. There were 11 852 males and 1 411 females, aged from 18 to 102 years, with a median age of 64 years. Of 13 263 patients, 9 995 with compression treatment after tension-free inguinal hernia repair were divided into compression group and 3 268 without compression treatment after tension-free inguinal hernia repair were divided into non-compression group. Observation indicators: (1) compression treatment of patients in the compression group; (2) occurrence of VTE after tension-free inguinal hernia repair in the two groups; (3) analysis of influencing factors for VTE after tension-free inguinal hernia repair. Follow-up using telephone interview was performed to detect history of patient's thrombosis, medical history of patient's family and the incidence of postoperative VTE up to February 2018. Measurement data with skewed distribution were represented as M ( P25, P75) or M (range), and comparison between groups was analyzed using the Wilcoxon rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test. Univariate analysis and multivariate analysis were conducted using the Logistic regression model. Results:(1) Compression treatment of patients in the compression group: of the 9 995 patients in the compression group, 6 086 underwent compression treatment with 0.5 kg of sandbag or 500 mL of packed 0.9% sodium chloride solution, 1 881 underwent compression treatment with trusses, 745 underwent compression treatment with girdles, 675 underwent compression treatment with elastic underwear combined with 0.5 kg of sandbag, and 608 underwent compression treatment with elastic underwear. (2) Occurrence of VTE after tension-free inguinal hernia repair in the two groups: patients of the two groups after matching were followed up. Occurrence of VTE after matching were 15 and 1 in the compression group and non-compression group, respectively, showing no significant difference between the two groups ( χ2=2.010, P>0.05). (3) Analysis of influencing factors for VTE after tension-free inguinal hernia repair: results of univariate analysis showed that cases with varix of lower limb, cases with oral contracep-tives or hormone replacement therapy history, cases with VTE history, clinical classification, clinical typing, surgical method, cases with anticoagulant drugs history, cases undergoing oral antiplatelet drugs, cases undergoing postoperative VTE prevention with medication were related factors for occurrence of VTE after tension-free inguinal hernia repair ( odds ratio=13.98, 37.71, 19.21, 4.43, 4.21, 0.07, 0.08, 0.10, 31.04, 95% confidence interval: 3.15?62.11, 8.35?170.24, 6.15?60.00, 1.43?13.76, 1.20?14.82, 0.01?0.49, 0.02?0.27, 0.04?0.29, 8.53?112.93, P<0.05). Results of multivariate analysis showed that cases with VTE history and surgical method were independent influencing factors for occurrence of VTE after tension-free inguinal hernia repair ( odds ratio=7.78, 11.19, 95% confidence interval: 2.06?29.42, 1.45?86.55, P<0.05). Conclusion:Cases with VTE history and surgical method are independent influencing factors for occurrence of VTE after tension-free inguinal hernia repair.

One of the most common birth defects is cleft palate only (CPO) of which non-syndromic cleft palate only (NSCPO) accounts for 50%. NSCPO is a complex disease where multiple genes and environmental factors contribute to its risk. Unlike non-syndromic cleft lip with or without cleft palate (NSCL/P), previous genome-wide association studies only identified a few common genetic variations achieving genome-wide significance. This review summarizes the recent findings on genetic epidemiology of NSCPO. According to the current evidence, the candidate genes are divided into three categories: candidate genes with strong evidence, candidate genes with suggestive evidence, and candidate genes with inadequate evidence. The findings of epigenetic studies, the next generation sequencing studies, interaction analysis on NSCPO are also reviewed.

Objective:To compare the outcomes of low-dose-rate prostate brachytherapy (BT) and radical prostatectomy (RP) in patients with T 1c-T 3a prostate cancer. Methods:A group of 745 patients with T 1c-T 3a prostate cancer between January 2010 and August 2017 at Peking Union Medical College Hospital were identified. The records of these patients, who were followed up for a minimum of 2 years, were reviewed. 384 cases received BT. Their characters included age(72.1±6.6), tPSA (12.4±6.1) ng/ml, prostate volume (33.6±13.8) ml, Gleason grade group (2.0±1.2). In this group, T 1c-T 2a stage was diagnosed in 189 cases, T 2b-T 2c stage in 182 cases and T 3a stage in 13 cases.361 cases received RP. Their characters included age(65.7±6.2), tPSA(12.6±6.4) ng/ml, prostate volume (37.2±17.8) ml, Gleason grade group (1.9±1.2). In this group, T 1c-T 2a stage was diagnosed in 177 cases, T 2b-T 2c stage in 170 cases and T 3a stage in 14 cases.The log-rank test compared survival rates between the two modalities, and Cox regression identified factors associated with bRFS. Results:Median follow-up was 60 months. Kaplan-Meier analysis did not show any statistically significant differences in terms of cRFS( P=0.321), cancer specific survival (CSS, P=0.643) and overall survival (OS, P=0.565) rate between the two groups. BT was associated with improved bRFS compared to RP( P=0.018). Risk of biochemical recurrence was significantly lower with BT compared with RP in the patients with a biopsy Gleason grade group 2 and 3 ( P=0.008), or prostate volume ≤35 ml ( P=0.027), or tPSA ≤10 ng/ml ( P=0.013), or the clinical T stages of T 2b and T 2C( P=0.031), or in the intermediate-risk group according to NCCN risk classification ( P=0.003). On multivariate analysis of all 745 patients, age≤ 70 and T stage≥T 2b was associated with significantly shorter bRFS. Conclusions:BT produced equivalent cRFS, CSS and OS compared to RP, while it was associated with improved bRFS. BT On multivariate analysis of all 745 patients, age≤ 70 and T stage≥T 2b was associated with significantly lower bRFS.

Objective: Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a common birth defect with its genetic evidence widely explored. This study explored the potential the parent-of-origin (PoO) effect of WNT pathway on the risks of NSCL/P, using a case-parent trio design. Methods: Data on the single nucleotide polymorphism (SNP) of WNT genes were selected from a genome-wide association study (GWAS). A total of 806 Chinese non-syndromic cleft lip patients, with or without cleft palate (NSCL/P) case-parent trios, were gathered from an international consortium. PoO effect of WNT pathway genes and its haplotypes were explored by log-linear models. Additional Wald tests were performed to assess: a) the heterogeneity of PoO effect between different maternal exposures, b) the interaction between PoO effect, c) maternal exposure to environmental tobacco smoke (ETS), and d) multivitamin supplementation during pregnancy. The threshold for statistical significance was adjusted as 3.47×10^-4, according to Bonferroni correction. Results: After quality control, a total of 144 SNPs within seven genes were included for analyses, among which 8 SNPs were of potential PoO effect (P<0.05). However, none of them achieved the statistical significance after Bonferroni correction. The haplotype rs4074668-rs12725747 (T-A) on WNT9A showed significant PoO effect, based on the haplotype test for PoO (P=2.74×10^-4). In addition, no statistically significant interaction was found in further exploration of this haplotype under environmental exposures as ETS or multivitamin supplementation. Conclusions Genes in the WNT pathway may influence the NSCL/P risks through the potential PoO effect. Particularly, the haplotype rs4074668-rs12725747 (T-A) on WNT9A presented significant PoO effect on NSCL/P, statistically. From this current study, findings on WNT pathway related risks among the NSCL/P, need to be further validated by independent samples in the future.

Objective: To study serum HCV antibody (anti-HCV) with geographic distribution characteristics in Zhejiang Province. Methods: A stratified random cluster sampling method was used. Serum samples of the surveyed population were collected from selected hospitals, anti-HCV antibodies were examined, then hepatitis C infection rates among different genders, regions and age groups were analyzed. The anti-HCV rate was compared using the χ ² test. Results: The average anti-HCV positive rate in Zhejiang Province was 0.24% [95% confidence interval (CI): 0.16% ~ 0.32%]. The antibody positive rate in the plain area was 0.32% (95% CI: 0.19% ~ 0.45%), which was significantly higher than the coastal islands 0.05%(95% CI: 0.00% ~ 0.12%, χ ² = 7.638, P < 0.05). There was no significant difference between plain area and hilly area 0.22% (95% CI: 0.03% - 0.41%). There was no statistically significant difference in anti-HCV positive rates between males and females (χ ² = 2.238, P = 0.135). The highest positive rate of anti-HCV (0.93%) was in the population aged 56-60 years and the lowest in the population aged less than 20 years. Anti-HCV positive rate of all age groups in 2017 was lower than that of 2006 seroepidemiological study of hepatitis C. Conclusion Zhejiang Province is a region with low anti-HCV positive rate and the disease prevalence further reduced than 10 years ago. The positive rate of anti-HCV in plain areas is higher than islands. Middle-aged and elderly people are the age group with high prevalence, and the anti-HCV positive rate in people under 20 years old is exceptionally low. Gender differences in anti-HCV positive rate have little effect.