Obesity is an important manifestation of the imbalance of energy regulation, and its complications can cause irreparable damage to the body. Finding the pathogenesis of obesity at the molecular level can help fundamentally avoid these irreversible complications. Extended synaptotagmins (E-Syts) are proteins related to the formation of endoplasmic reticulum (ER) and plasma membrane (PM). Because of the short discovery time, there is huge room for exploration. In terms of the role of the established structure of E- Syts at the molecular level, it has a non-negligible link with the pathogenesis of obesity. Starting with the structure of hypothalamus, this paper reviews the literature evidence of this connection, hoping to find a new research angle for reducing the incidence of obesity.

Objective To investigate the advantages and efficacy of traction with titanium clips in endoscopic submucosal dissection(ESD)for large laterally spreading tumor(LST)in rectum and sigmoid colon.Methods 67 patients with large sigmoid or rectal LST underwent ESD from January 2018 to June 2022 were analyzed retrospectively,including 32 patients in Group A and 35 patients in Group B.Group A was treated with clip-line traction and group B was treated with traditional ESD.The size of lesion,the total operation time,the submucosal dissection time,submucosal dissection rate,submucosal injection number,en bloc resection rate,R0 resection rate,curative resection rate and complications of the two groups were compared.Results LST-G-M was the most common type and villous adenoma was the main pathology in both groups.There were no differences in en bloc resection rate,R0 resection rate and incidence of complications between the two groups.The average size of group A was(13.6±8.4)cm2,significantly larger than that in group B(9.3±4.7)cm2,the total operation time was(42.3±10.3)min in group A,significantly shorter than that in group B(47.9±10.1)min,submucosal dissection time was(30.7±8.2)min in group A,significantly shorter than that in group B(36.1±7.6)min,submucosal injection number was(2.7±1.1)times in group A,significantly less than that in group B(3.5±1.2)times,submucosal dissection rate was(0.4±0.2)cm2/min in group A,significantly faster than that in group B(0.2±0.1)cm2/min,the differences were statistically significant(P<0.05).Conclusion Compared with traditional ESD,clip-line traction can provide a better surgical field and more effective dissection for large LST in rectum and sigmoid colon.

Objective:To investigate the effectiveness and safety of domestic upper gastrointestinal endoscopic ultrasound (EUS).Methods:A total of 160 patients undergoing EUS at Shengjing Hospital of China Medical University (Center1) and Shenzhen People's Hospital (Center 2) from March to July 2021 were randomly selected by stratified blocked randomization, and were treated with SonoScape EG-UG5T (the test group) or Fujifilm EG-580UT (the control group). The primary outcome was the ultrasound image quality excellence rate, and the comparison was verified by non-inferiority. The secondary outcomes were the endoscopic image quality excellence rate, the operational performance excellence rate, and the system stability evaluation. The safety evaluation was based on the occurrence of intraoperative and postoperative adverse events in the subjects.Results:In the intention-to-treat analysis set (ITT), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (77/77), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.8%). In the per protocol analysis set (PPS), the excellence rate of ultrasound image quality in the test group and the control group was 100.0% (78/78) and 100.0% (75/75), respectively. The rate difference between the two groups was 0.0% (95% CI: -4.7%-4.9%). The lower limit of the confidence interval of ultrasound image quality excellence rate of both data sets was greater than the non-inferiority threshold value of -8%, which inferred that the non-inferiority hypothesis of the test machine non-inferior to the control machine was valid. The endoscopic image quality excellence rate and the operational performance excellence rate of the test group and the control group was 100.0% in both the ITT and PPS analyses, and there was no statistically significant difference between the two groups ( P=1.000). The system instability event rate was 0.0% (0/78) in the test group and 3.9% (3/77) in the control group ( P=0.120). No adverse event occurred in either group. Conclusion:The domestic upper gastrointestinal endoscopic ultrasound is standard-compliant for clinical application under normal conditions in terms of effectiveness, safety, and stability.

Objective:To explore the clinical efficacy and safety of daratumumab-based combined regimens for relapsed/refractory multiple myeloma (RRMM).Methods:A retrospective case series study was conducted. The clinical data of 38 patients with RRMM in Jining NO.1 People's Hospital from Janunary 2020 to December 2022 were retrospectively analyzed. All patients were treated with daratumumab-based combined regimens. The Dd regimen (12 cases) was treated with daratumumab and dexamethasone, the DPD regimen (20 cases) was treated with pomalodomide based on the Dd regimen, the DVD regimen (6 cases) was treated with bortezomib based on the Dd regimen. The therapeutic efficacy and adverse reactions of all groups were analyzed. Kaplan-Meier method was used for survival analysis.Results:The median follow-up time was 9.5 months (1.0 months, 32.5 months) and the median treatmemt time was 6.2 months (3.2 months, 25.6 months). Among 38 patients, 7 cases (18.7%) achieved complete remission, 9 cases (23.6%) achieved very good partial remission, 10 cases (26.3%) achieved partial remission, 4 cases (10.5%) achieved minimal remission, 5 cases (13.1%) achieved stable disease, 3 cases (7.9%) had the progression of the disease. The overall response rate (ORR) was 78.9% (30/38). The ORR was 66.7%(8/12), 83.3%(5/6), 85.0%(17/20), respectively in the Dd group, DVD group and DPD group. There was no statistically significant difference in the ORR between the DVD group and DPD group ( χ2 = 0.01, P>0.05); there was no statistically significant difference in the ORR between the DVD group and Dd group ( χ2 = 0.55, P>0.05); there was no statistically significant difference in the ORR between the DPD group and Dd group ( χ2 = 1.47, P>0.05). The median progression-free survival (PFS) time was 12.5 months (95% CI: 8.5-24.2 months),the median overall survival (OS) time was not reached, and the 1-year OS rate was 89.4%. Among 38 patients, the main adverse reactions during treatment were infusion-related adverse reactions in 5 cases, grade 3 neutropenia in 7 cases, grade 3 thrombocytopenia in 9 cases, severe anemia in 12 cases; no one had drug discontinuation or drug reduction due to the intolerance of adverse reactions. Conclusions:Daratumumab-based combined regimens in the treatment of RRMM show a favorable efficacy and safety.

Objective:To explore the clinical effect and safety of venetoclax combined with azacitidine for high-risk myelodysplastic syndromes (MDS).Methods:A retrospective case series study was conducted. The clinical data of 48 patients with high-risk MDS in Jining No.1 People's Hospital from January 2020 to May 2023 were collected, and all patients were divided into the control group (20 cases) and the test group (28 cases) according to medications. The control group was treated with azacitidine alone, and the test group was treated with venetoclax combined with azacitidine regimen. The total effective rate and adverse reactions of the 2 groups were compared after 3 courses of treatment.Results:Among 48 patients, 30 cases were male and 18 cases were females; the median onset age [ M ( Q1, Q3)] was 62 years (54 years, 75 years). There were no statistically significant differences in gender, age, white blood cell count, neutrophil count, hemoglobin, platelet count, bone marrow original cells proportion between the 2 groups (all P>0.05). After 3 courses of treatment, the total effective rate in the test group was 75% (22/28), and the rate in the control group was 45% (9/20), and there was a statistically significant difference between the two groups ( χ2 = 5.74, P<0.05). The incidence of grade 3 and the above adverse reactions in the control group and the test group was 25% (5/20), 54% (15/28), respectively, and the difference was statistically significant ( χ2 = 1.62, P>0.05). Conclusions:Venetoclax combined with azacitidine regimen for high-risk MDS can improve the clinical efficacy, and the adverse reactions can be tolerated.

Objective:To explore the incidence of secondary hemophagocytic lymphohistiocytosis (sHLH) in elderly patients with severe SARS-CoV-2 infection, and to analyze and summarize its clinical features and risk factors for early identification of high-risk groups.Methods:A retrospective cohort study was conducted. From January to May 2020, No. 960 Hospital of People's Liberation Army, the Second Hospital Affiliated to Cheeloo College of Medicine of Shandong Province, the First Rehabilitation Hospital of Shandong Province, the Public Health Clinical Center Affiliated to Shandong University, and Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine received 248 patients over 60 years old who were diagnosed with severe SARS-CoV-2 infection during their assistance to Hubei or support for diagnosis and treatment of SARS-CoV-2 infection in Shandong Province. The clinical data of patients were collected. According to the hemophagocytic lymphohistiocytosis diagnosis scoring (HScore) criteria, the patients were divided into sHLH group (HScore > 169) and non-sHLH group (HScore < 98). The demographic data, clinical features, laboratory results, the proportion of organ failure and 60-day mortality of patients were collected and compared between the two groups. The risk factors of sHLH and 60-day death were evaluated through binary multivariate Logistic regression analysis in elderly patients with severe SARS-CoV-2 infection. The receiver operator characteristic curve (ROC curve) was plotted to analyze the diagnostic value of indicators only or combined for sHLH.Results:Among 248 elderly patients with severe SARS-CoV-2 infection, 82 patients with incomplete data and untraceable clinical outcomes, and 35 patients with HScore of 98-169 were excluded. Finally, 131 patients were enrolled in the final follow-up and statistics, including 25 patients in the sHLH group and 106 patients in the non-sHLH group. Compared with the non-sHLH group, plasma albumin (ALB), hemoglobin (Hb), lymphocyte count (LYM), platelet count (PLT), fibrinogen (Fib) and prealbumin (PAB) in the sHLH group were significantly reduced, while alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), MB isoenzyme of creatine kinase (CK-MB), serum creatinine (SCr), C-reactive protein (CRP), D-dimer, ferritin (Fer), lactate dehydrogenase (LDH), procalcitonin (PCT), cardiac troponin I (cTnI), triglycerides (TG), interleukin-6 (IL-6), total bilirubin (TBil) were significantly higher. The fever and fatigue in the sHLH group were more severe than those in the non-sHLH group, and the patients in the sHLH group had higher rates of shock, acute kidney injury, liver dysfunction, and cardiac injury than the non-sHLH group. The 60-day mortality of patient in the sHLH group was significantly higher than that in the non-sHLH group [84.0% (21/25) vs. 40.6% (43/106), P < 0.01]. Binary multivariate Logistic regression analysis showed that high Fer [odds ratio ( OR) = 0.997, 95% confidence interval (95% CI) was 0.996-0.998], D-dimer ( OR = 0.960, 95% CI was 0.944-0.977), LDH ( OR = 0.998, 95% CI was 0.997-0.999) and TG ( OR = 0.706, 95% CI was 0.579-0.860) were independent risk factors for sHLH in elderly patients with severe SARS-CoV-2 infection (all P < 0.01), while elevated Fer ( OR = 1.001, 95% CI was 1.001-1.002), LDH ( OR = 1.004, 95% CI was 1.002-1.005) and D-dimer ( OR = 1.036, 95% CI was 1.018-1.055) were independent risk factors for 60-day death of patients (all P < 0.01). The death risk of the sHLH patients was 7.692 times higher than that of the non-sHLH patients ( OR = 7.692, 95% CI was 2.466-23.987, P = 0.000). ROC curve analysis showed that a three-composite-index composed of LDH, D-dimer and TG had good diagnostic value for sHLH in elderly patients with severe SARS-CoV-2 infection [area under the ROC curve (AUC) = 0.920, 95% CI was 0.866-0.973, P = 0.000]. Conclusions:Elderly patients with severe SARS-CoV-2 infection complicated by sHLH tend to be critically ill and have refractory status and worse prognosis. High Fer, LDH, D-dimer and TG are independent risk factors for sHLH, and are highly suggestive of poor outcome. The comprehensive index composed of LDH, D-dimer and TG has good diagnostic value, and can be used as an early screening tool for sHLH in elderly patients with severe SARS-CoV-2 infection.

Letrozole,a third generation non-steroidal aromatase inhibitor,has been approved for the treatment of breast cancer in women.In recent years,it has been used in the field of growth and development in children,such as childhood dwarfism,somatic delayed pubertal growth and precocious puberty,but the long-term effects on liver and kidney function,lipid metabolism,reproductive function and bone metabolism are unclear.Studies have shown that letrozole can cause abnormal testicular morphology,changes in seminiferous tubules and interstitial tissues,reduce bone density,affect the bal-ance of bone metabolism,and cause cognitive impairment and apoptosis of nerve cells.The mecha-nism of reproductive toxicity of letrozole may be related to its influence on the development and matura-tion of testicular cells,the expression of sex hormones and gonadotropins in vivo,and the distribution and expression of estrogen receptors in testicular tissues.The mechanism of bone metabolic toxicity is related to its increase in the proliferation and differentiation of osteoclasts induced by receptor activator of NF-κB ligand,as well as the increase of apoptosis,oxidative stress and NF-κB activity of osteo-blasts.The mechanism of cognitive toxicity is related to its regulation of classical and nonclassical effects of the hippocampus,reduction of glutamate uptake by astrocytes,and reduction of L-type calcium channel blockade of caspase 3 activation.This article is to provide reference for safe and effective use of letrozole in clinical pediatrics.

Objective: To investigate the epidemiological characteristics of sexually transmitted diseases (STDs) in Zhejiang Province from 2018 to 2022, so as to provide insights into improving STDs prevention and control strategies. Methods: Data of syphilis, gonorrhea, condyloma acuminatum, genital herpes and genital Chlamydia trachomatis infections reported in Zhejiang Province from 2018 to 2022 were collected from the Infectious Disease Surveillance System of Chinese Disease Prevention and Control Information System. The temporal, spatial and population distribution of STDs were analyzed, and the trends in incidence of STDs were evaluated using annual percent change (APC). Results: A total of 386 770 STDs cases were reported in Zhejiang Province from 2018 to 2022, with mean annual reported incidence of 127.80/105. The mean annual reported incidence from high to low was syphilis (44.11/105), genital Chlamydia trachomatis infections (40.20/105), gonorrhea (24.92/105), condyloma acuminatum (13.32/105), and genital herpes (5.34/105). The incidence of STDs appeared a tendency towards a decline from 2018 to 2022 (APC=-9.332%, P<0.05), with an average annual growth rate of -9.41%. Syphilis (APC=-11.536%, P<0.05), condyloma acuminatum (APC=-7.509%, P<0.05), and genital Chlamydia trachomatis infections (APC=-9.009%, P<0.05) showed a appeared a tendency towards a decline. The top three highest reported incidence were reported in Hangzhou City (185.98/105), Taizhou City (133.85/105) and Lishui City (122.73/105), respectively. The mean annual reported incidence of females was higher than that of males (140.60/105 vs. 117.83/105; P<0.05). Most STDs cases were at ages of 20 to 49 years (265 314 cases, 68.60%). Farmers (118 096 cases, 30.53%), household and unemployed personnel (85 924 cases, 22.22%) were the predominant occupation. Conclusions The incidence of STDs appeared a tendency towards a decline in Zhejiang Province from 2018 to 2022, with regional differences in incidence. People at ages of 20 to 49 years, farmers, household and unemployed personnel are high-risk populations for STDs.

Objective:To investigate the correlation between serum brain-derived neurotrophic factor (BDNF) and post-stroke cognitive impairment (PSCI) in patients with acute ischemic stroke, and to evaluate its predictive value for PSCI.Methods:Patients with acute ischemic stroke admitted to the Affiliated Hospital of Jining Medical University from April 2018 to September 2020 were prospectively enrolled. Cognitive impairment was assessed by Montreal Cognitive Assessment (MoCA) at 3 months after onset. Multivariate logistic analysis was used to determine the independent correlation between serum BDNF and PSCI, and receiver operating characteristics (ROC) curve was used to evaluate its predictive value for PSCI. Results:A total of 511 patients with acute ischemic stroke were enrolled, including 332 males (65.0%), aged 60.67±10.18 (range 49-80) years. The median score of the National Institutes of Health Stroke Scale (NIHSS) at the baseline was 5.0 (interquartile range 2.7-6.7), and 413 patients (80.8%) had anterior circulation stroke. The median of serum BDNF was 11.54 μg/L (interquartile range 6.13-16.25 μg/L). PSCI occurred in 310 patients (60.7%). Univariate analysis showed that there were significant differences in age, history of previous transient ischemic attack, baseline NIHSS score and serum BDNF between the PSCI group and the non-PSCI group (all P<0.05). Multivariate logistic analysis showed that there was a significant independent correlation between serum BDNF and PSCI (odds ratio 0.514, 95% confidence interval 0.356-0.807; P=0.005). ROC curve analysis showed that the area under the curve of serum BDNF predicting PSCI was 0.863 (95% confidence interval 0.830-0.896; P<0.001). The best cut-off value was 10.78 μg/L, and the sensitivity and specificity were 74.9% and 86.8% respectively. Conclusion:Higher baseline serum BDNF was a protective factor for PSCI and had good predictive value for PSCI.

Enterohepatic circulation plays an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Bile acid is the basic substance of enterohepatic circulation and plays an important role in lipid metabolism, intestinal flora regulation, and host immunity. This article summarizes the research advances in bile acid which acts as a signal molecule to activate bile acid receptors in the liver and intestine, such as farnesoid X receptor, G protein-coupled receptor 5, pregnane X receptor, and vitamin D receptor, and is thus involved in the pathogenesis of NAFLD. It is expected to develop effective drugs for the treatment of NALFD based on the above targets, but there is still a need for further exploration.