To compare the effect of endoscopic submucosal dissection (ESD) and endoscopic pedicle ligation with nylon rope or metal clip followed by electrical resection on postoperative hemorrhage for thick colorectal pedicle polyps, clinical data of patients undergoing endoscopic polypectomy in Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University) from January 2018 to November 2022 were retrospectively collected, and the patients were divided into ESD group and pre-ligation group according to different treatment methods. Postoperative bleeding data of the two groups were compared and analyzed. A total of 265 patients were included, including 124 in ESD group and 141 in pre-ligation group. There were no significant differences in gender, age, polyp sites, polyp diameter or pedicle diameter between the two groups ( P>0.05). The postoperative bleeding rate in the ESD group was significantly lower than that in the pre-ligation group [4.0% (5/124) VS 10.6% (15/141), χ2=4.126, P=0.042]. Compared with ESD group, more bleeding occurred in the left colon in the pre-ligation group, with statistically significant difference [40.0% (2/5) VS 93.3% (14/15), P=0.032]. The hospital stay was longer in the ESD group than that in the pre-ligation group (4.6±1.9 days VS 3.4±1.5 days, t=5.641, P<0.001). ESD is more effective than pre-ligation in reducing postoperative hemorrhage for coarse pedicle colorectal polyps, especially for those on distal colon.

Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.

Objective:To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice.Methods:Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group ( n=5) and a high-fat feeding modeling group ( n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group ( n=7) and a UC-MSCs treatment group ( n=7). The UC-MSCs treatment group was given UC-MSCs (1×10 6/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1β (IL-1β) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1β in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results:In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1β decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1β secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3β (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions:UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.

【Objective】 To investigate the clinicopathological features and prognosis of clear cell papillary renal cell carcinoma (CCPRCC). 【Methods】 The clinicopathological and follow-up data of 40 CCPRCC patients treated during Jun. 2011 and Oct.2021 were retrospectively analyzed. The prognosis was compared with that of 40 cases of clear cell renal cell carcinoma (ccRCC) and 19 cases of papillary renal cell carcinoma (PRCC) treated in the same period. Survival analysis was performed by Log-rank test and Kaplan-Meier survival curves were plotted. 【Results】 Among the 40 patients, 28 were male and 12 were female, aged 31-84 years; 38 cases had unilateral and 2 cases had bilateral tumors; 3 cases had multifocal lesions. All patients received surgery. The maximum diameter of the masses ranged from 3.0 to 95.0 mm, with an average of (27.6±18.1) mm. Pathological grade was Fuhrman 1-2 in all cases. Immunohistochemical tests were positive for CK7 and CA-IX. During the follow-up of 5-129 (average 56) months, 1 case died after bone metastasis, 2 had ipsilateral recurrence, and 1 developed primary esophageal cancer. CCPRCC patients had a significantly better prognosis than CCRCC (P<0.001) and PRCC (P=0.005) patients, while there was no significant difference in the prognosis between CCRCC and PRCC patients (P=0.93). 【Conclusions】 CCPRCC has low malignancy. The diagnosis relies on characteristic pathological and immunohistochemical features. Surgery is an effective treatment. CCPRCC has a better overall prognosis than CCRCC and PRCC.

Congenital generalized lipodystrophy type 1 (CGL1) is an autosomal recessive genetic disease caused by mutations in AGPAT2 gene. The main clinical mainifestations include body subcutaneous fat loss, muscle hypertrophy, obvious subcutaneous veins, pseudoacromegaly, hirsutism, and acanthosis nigricans. What′s more, CGL1 is always accompanied by metabolic diseases. Therefore, it is easily misdiagnosed as metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, acromegaly, or Cushing′s syndrome. Meanwhile, it is difficult to distinguish it from partial lipoatrophy syndrome. In this article, we present clinical and molecular characteristics of a patient with CGL1 and review mutations reported in literature to replenish current knowledge about this orphan disease.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To investigate the best neutralization ratio of protamine and heparin during off-pump coronary artery bypass grafting(OPCABG) by analyzing the advantages and disadvantages of heparin residue after OPCABG.Methods:From July 2018 to January 2019, 112 patients undergoing elective OPCABG were included in this study. The patients’ whole blood was drawn at 2 time points, including before entering operating room and entering intensive care unit, to receive thrombelastography(TEG) and heparinase-modified thromboelastography(hmTEG) . Conventional coagulation indexes such as activated coagulation time(ACT) were also detected. All the patients were divided into 3 groups, the non-heparin residue group(30 cases), heparin residue group 1(42 cases) and heparin residue group 2(40 cases) according to the laboratory results of TEG, hmTEG and ACT. We observed the dosage of each group of protamine and heparin, as well as the ratio of heparin and protamine. The changes of R time in TEG and ACT between 3 groups were analyzed and compared. Postoperative chest tube drainage at postoperative 12 h and 48 h, cTnI peak value, incidence of perioperative myocardial infarction(MI), incidence of reoperation and poor wound healing, amount of blood loss and transfusion, and acute renal injury were compared between the 3 groups.Results:No significant trio-group differences existed in basic clinical characteristics(all P>0.05). Postoperative R(CKH)time was similar in the 3 groups( P>0.05). Comparing with heparin residue group 1 and heparin residue group 2, the ACT after protamine neutralizing heparin and postoperative R time were decreased, the dosage of protamine, ratio of heparin and protamine, cTnI peak value were increased in the non-heparin residue group( P<0.05). Comparing with heparin residue group 2, the dosage of heparin, postoperative chest tube drainage at postoperative 12h and 48h, amount of blood transfusion and transfusion probability were significantly decreased in non-heparin residue group( P<0.05), but compared with group 1 of heparin residue, there was no significant difference in the above indexes( P>0.05). The perioperative myocardial infarction, incidence of reoperation and poor wound healing, postoperative acute renal injury and time of in ICU stay showed no significant differences between the 3 groups( P>0.05). Conclusion:Moderate heparin residue after OPCAB suggests that it has myocardial protective effect, and does not significantly increase the risk of bleeding. A large number of heparin residues can affect the coagulation function and lead to bleeding tendency, increase the amount of blood loss and transfusion. It is reasonable to make ACT after protamine neutralize heparin higher than the level of ACT before operation, and not higher than 20% of the level before operation.

Objective    To explore the relationship between glycated hemoglobin (HbA1c) level and blood glucose fluctuations after coronary artery bypass grafting (CABG) and adverse events in non-diabetic patients, thus providing theoretical support for intensive preoperative blood glucose management in patients undergoing CABG surgery. Methods    A total of 304 patients undergoing CABG with or without valvular surgery from October 2013 to December 2017 were enrolled in this prospective, single-center, observational cohort study. We classified them into two different groups which were a low-level group and a high-level group according to the HbA1c level. There were 102 males and 37 females, aged 36–85 (61.5±9.5) years in the low-level group, and 118 males and 47 females aged 34–85 (63.1±9.4) years in the high-level group. The main results were different in hospital mortality and perioperative complications including in-hospital death, myocardial infarction, sternal incision infection, new stroke, new-onset renal failure and multiple organ failure. To assess the effects of confounding factors, multivariate logistic regression analysis was used. Results     Postoperative blood glucose fluctuation was more pronounced in the high-level group than that in the low-level group before admission [0.8 (0.6, 1.2) mmol/L vs. 1.0 (0.8, 1.8) mmol/L, P<0.01]. This study also suggested that the  incidence of major adverse events was significantly lower in the low-level group compared with the high-level group (P=0.001). Multivariate logistic regression analyses to correct the influence of other confounding factors showed that HbA1c (OR=2.773, P=0.002) and postoperative blood glucose fluctuations (OR=3.091, P<0.001) could still predict the occurrence of postoperative adverse events. Conclusion    HbA1c on admission can effectively predict blood glucose fluctuations in 24 hours after surgery. Secondly, HbA1c on admission and postoperative blood glucose fluctuations can further predict postoperative adverse events. It is suggested that we control the patient's preoperative HbA1c at a low level, which is beneficial to control postoperative blood glucose fluctuation and postoperative adverse events.

The widespread application of next generation sequencing (NGS) in clinical settings has enabled testing, diagnosis, treatment and prevention of genetic diseases. However, many issues have arisen in the meanwhile. One of the most pressing issues is the lack of standards for reporting genetic test results across different service providers. The First Forum on Standards and Specifications for Clinical Genetic Testing was held to address the issue in Shenzhen, China, on October 28, 2017. Participants, including geneticists, clinicians, and representatives of genetic testing service providers, discussed problems of clinical genetic testing services across in China and shared opinions on principles, challenges, and standards for reporting clinical genetic test results. Here we summarize expert opinions presented at the seminar and report the consensus, which will serve as a basis for the development of standards and guidelines for reporting of clinical genetic testing results, in order to promote the standardization and regulation of genetic testing services in China.

Objective The aim of the study is to evaluate the early and long-term outcomes of mitral valve repair for degenerative mitral regurgitation.Methods From January 2003 to December 2015,clinical profiles of 1 903 patients with degenerative mitral regurgitation who underwent mitral valve repair at our institution were analyzed retrospectively.There were 1 312 males (68.9 ％) and 591 females (31.1％) the mean age was (54.2 ± 13.1) years.Early and long-term outcomes were summarized and risk factors for adverse events were assessed.Results There were 35 in-hospital deaths(1.8％) and in-hospital mortality for isolated mitral valve repair was 0.9％ (10/1 163).Perioperative complications included central nerve system complications(0.7％),respiratory failure requiring tracheotomy(1.8％),acute renal injury requiring hemodialysis(1.2％) and reoperation for bleeding(0.7 ％).NYHA function class Ⅲ-Ⅳ (OR =3.65),atrial fibrillation (OR =2.85) and ejection fraction ＜0.6(OR =2.34) were identified as independent risk factors for in-hospital mortality.12 years over follow-up,overall survival,freedom from reoperation for mitral valve and freedom from recurrent moderate/severe regurgitation were 85％ 、91％ and 75％,respectively.Age ＞ 60 years(HR =7.43),preoperative stroke(HR =6.51),ejection fraction ＜ 0.6 (HR =3.87),left ventricular end-systolic dimension ＞ 40 mm (HR =3.98) and pulmonary systolic pressure ＞ 50 mmHg (1 mmHg =0.133 kPa) (HR =2.85) were independent predictive factors for late death.Ejection fraction ＜ 0.6 (HR =4.01),left ventricular end-diastolic dimension ＞ 60 mm(HR =1.88),leaflet lesion involving anterior leaflet (HR =2.40) and residue mild regurgitation(HR =4.17) were independent predictors for late recurrent regurgitation.Leaflet lesion involving anterior leaflet(HR =2.40) and residue mild regurgitation (HR =3.35) were independent predictor for late reoperation for mitral valve.Conclusion Mitral valve repair is safe and effective in degenerative mitral regurgitation.Early surgical intervention for asymptomatic patients with preserved left ventricular function before onset of atrial fibrillation and pulmonary artery hypertension is associated with decreased incidence of adverse events and improved long-term outcomes.Early surgical intervention should be restricted in experienced high-volume centers.