Objective: To investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

Sumoylation is a newly discovered post-translational modification, in which a small ubiquitin-like modifier (SUMO) is covalently conjugated to a lysine residue in a target protein. This provides an efficient way to modulate the activity, stability and subcellular localization of a wide variety of substrates. Sumoylation plays a key role in the occurrence and development of type 2 diabetes mellitus (T2DM). This paper addresses the relationship between sumoylation and T2DM in regulation of pancreatic β-cell function, the metabolic order in skeletal muscles, liver and other organs and diabetes-associated complications. A deeper knowledge of sumoylation may enable us to better understand the pathogenesis of T2DM and sumoylation system at the molecular level, which can help provide new ideas for the early diagnosis and subsequent treatment of T2DM and its associated complications.

Objective To analyze the burden and epidemic trends of gastric cancer in China from 1990 to 2021, and to provide a scientific basis for the formulation of effective prevention and control strategies. Methods　Data from the 2021 Global Burden of Disease (GBD) database were used to extract the number of the incidence, prevalence, and death cases, as well as the disability-adjusted life years (DALY) for gastric cancer in China from 1990 to 2021. The corresponding crude rates and age-standardized rates were calculated. The Joinpoint regression model was employed to analyze the trends in the burden of gastric cancer, and a comprehensive examination was conducted from multiple dimensions including age, gender, and time. Results From 1990 to 2021, the age-standardized incidence rate (ASIR) of gastric cancer in China decreased from 48.03 per 100,000 to 29.05 per 100,000, the age-standardized prevalence rate (ASPR) decreased from 67.17 per 100,000 to 57.23 per 100,000, the age-standardized mortality rate (ASMR) decreased from 46.05 per 100,000 to 21.51 per 100,000, and the age-standardized DALY rate (ASDR) decreased from 1181.61 per 100,000 to 501.26 per 100,000. The AAPCs of ASIR, ASPR, ASMR, and ASDR were -1.61%, -0.50%, -2.44%, and -2.75%, respectively. The incidence, prevalence, mortality and DALY rates showed a trend of increasing first and then decreasing with age. Although females had higher incidence, prevalence, mortality, and DALY numbers in the older age groups, males exhibited higher crude rates across all age groups. Conclusion　The overall disease burden of gastric cancer in China showed a downward trend from 1990 to 2021, and men and middle-aged and elderly people are the key populations for prevention and control efforts.

Objective: To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies. Methods: Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models. Results: A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively. Conclusions Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.

Objective To analyze the epidemiological characteristics of lung cancer death in Gansu Province, and to provide a theoretical basis for formulating the prevention and control measures of lung cancer. Methods The lung cancer death data from national monitoring sites in Gansu Province from 2014 to 2023 were selected. Excel2013 and SPSS17.0 were used to calculate lung cancer mortality, standardized mortality, potential years of life lost (PYLL), potential years of life lost rate, standardized potential years of life lost rate, and average years of life lost (AYLL). The annual percent change (APC) of the crude lung cancer mortality rate and standardized mortality rate was calculated using Joinpiont 4.8.0.1 software. The mortality difference decomposition method was used to analyze demographic and non-demographic factors. Results From 2014 to 2023, the crude mortality rate of lung cancer among the residents of the monitoring sites in Gansu Province showed an increasing trend. The mortality rate of males was higher than that of females. The mortality rate in urban areas was higher than that in rural areas. The population structure was the main factor leading to the increase of lung cancer mortality rate in urban areas, while other non-demographic factors were the main factors leading to the increase of lung cancer mortality rate in rural areas. The crude lung cancer mortality rate was low at the age of < 30, and then the mortality rate increased with age. Lung cancer PYLL was higher in males than in females, and AYLL was higher in females than in males. Conclusion The mortality rate of lung cancer in the monitoring sites in Gansu Province is on the rise. The urban areas and male population are the key areas and groups for intervention. It is suggested to further strengthen the early screening and intervention of lung cancer to reduce the mortality rate of lung cancer.

Objective     To evaluate the clinical effectiveness of valve-sparing aortic root replacement (VSARR) in the treatment of patients with dilated aortic root after operation for tetralogy of Fallot (TOF). Methods     A retrospective analysis was conducted on clinical data of TOF patients with aortic root dilation who underwent VSARR in our hospital from 2016 to 2022. Results     Finally 14 patients were collected, including 8 males and 6 females, with a median age of 22 years ranging from 12-48 years. Among them, 5 patients had severe aortic valve regurgitation, 4 moderate regurgitation, and 5 mild or no regurgitation. Six patients had sinus of valsalva dilation, and 8 significant dilation of the ascending aorta. One patient had residual shunt due to ventricular septal defect, and 9 severe pulmonary valve regurgitation. The David procedure was performed in 10 patients, Yacoub procedure in 2 patients, and Florida sleeve in 2 patients. There was no perioperative mortality in the group. The median follow-up time was 2.9 years (ranging from 0.4 to 6.0 years). One patient had mild aortic valve regurgitation, and the rest had minimal or no regurgitation. One patient had mild stenosis of the left ventricular outflow tract, and the rest patients had no obvious stenosis. Conclusion     VSARR is a satisfactory treatment for aortic root dilation in patients with TOF, with no significant increase in the incidence of left ventricular outflow tract stenosis or aortic regurgitation during mid-term follow-up.

By consulting the ancient and modern literature， the textual research of Pharbitidis Semen has been conducted to clarify the name， origin， distribution of production areas， quality specification， harvesting， processing and so on， so as to provide reference for the development and utilization of the relevant famous classical formulas. Through textual research， it can be seen that Pharbitidis Semen was first published in Mingyi Bielu（《名医别录》）， and all dynasties have taken Qianniuzi as the correct name. Based on the original research， the main source of Pharbitidis Semen used in previous dynasties is the dried mature seeds of Pharbitis nil， which is consistent in ancient and modern times. The white Pharbitidis Semen appearing in Compendium of Materia Medica（《本草纲目》） from Ming dynasty is similar to the present P. purpurea. It is produced all over the country， and the quality is better if the particles are full and free of impurities. In ancient times， the harvesting time was mostly in the September. Now it is autumn. The fruits are ripe and harvested， dried to remove impurities for standby. In ancient times， the processing methods of Pharbitidis Semen were mainly wine steaming， steaming and frying until half cooked and grinding the head and end. In modern times， they have been simplified to stir-frying method. The nature， taste， meridian tropism and their effects also change supplements with the deepening of practice. Before the Ming dynasty， they were all bitter， cold and toxic. In the Ming dynasty， there appeared the characteristics of pungent， hot and small poisonous. The efficacy has evolved from controlling low Qi， curing foot edema， removing wind toxin， and facilitating urination to facilitating water and defecation， eliminating phlegm and drinking， and eliminating accumulated insects. The main clinical contraindications are those with weak spleen and kidney， those with weak spleen and stomach， pregnant women， and should not be used with croton and croton cream. Based on the textual research， it is suggested that when developing the classic famous formula with Pharbitidis Semen as the main raw material in the future， it is clear that the source should be the dried mature seeds of Pharbitis nil（black product is its black-brown seeds， white product is its beige seeds）. The processing requirements indicated in the original formula are all processed according to the requirements， and the raw product is recommended to be used as medicine if not specified.

Objective To investigate the effect of paeoniflorin on aerobic glycolysis of macrophages induced by resiquimod.Methods THP-1 cells were treated with phorbol ester(PM A)to differentiate into macrophages.The cells were divided into control group,model group and low,medium,high dose experimental group.The cells in the control group were cultured normally;in the model group,2 μg·mL-1 resiquimod was used to stimulate macrophages for 24 h to induce aerobic glycolysis.The low,medium and high dose experimental groups were treated with 1,10 and 100 μmol·L-1 paeoniflorin for 24 h on the basis of the model group.Cell activity was detected by cell counting kit-8(CCK-8)method.Lactate and glucose determination kit were used to detect lactate secretion and glucose consumption of cells in each group.The protein and mRNA expression levels of(PKM2)and(LDHA)were detected by Western blot and real-time fluorescence quantitative polynucleotide chain reaction(q-PCR)respectively.Immunofluorescence method was used to compare the fluorescence intensity of PKM2 in each group.Results After 24 h stimulation of THP-1 cells with 2 μg·mL-1 resiquimod,the glucose contents in cell culture supernatants of control group,model group and low,medium and high dose experimental groups were(14.70±0.44),(9.83±0.43),(10.68±0.29),(11.79±0.33)and(13.63±0.74)mmol·L-1;the lactate secreted by cells were(6.17±0.48),(11.94±0.55),(9.08±0.55),(7.79±0.66)and(6.50±0.55)mmol·L-1;the protein expression levels of PKM2 in cells were 1.00±0.00,1.33±0.18,1.02±0.17,0.74±0.17 and 0.73±0.18;the protein expression levels of LDHA were 1.00±0.00,1.20±0.09,0.90±0.14,0.76±0.12 and 0.78±0.17;the PKM2 mRNA levels were 1.00±0.09,2.11±0.23,1.98±0.31,1.38±0.25 and 0.93±0.32;the LDHA mRNA levels were 1.00±0.13,1.85±0.25,1.44±0.21,0.91±0.24 and 0.96±0.14;the average fluorescence intensities of PKM2 were 136.41±33.63,217.94±5.33,210.27±1.03,204.14±3.27 and 186.79±14.03.Compared with control group,the above indicators in model group showed statistically significant differences(P＜0.05,P＜0.01);compared with model group,the differences in the above indicators in medium and high dose experimental group were all statistically significant(P＜0.05,P＜0.01).Conclusion Paeoniflorin can inhibit the aerobic glycolysis of macrophages induced by resiquimod.

Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49％,101.88％and 101.89％,respectively,with 90％confidence intervals of 98.18％-111.20％,97.80％-106.13％and 97.87％-106.07％,all within the range of 80.00％-125.00％.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34％,103.55％and 102.98％,respectively with 90％confidence intervals of 101.69％-113.31％,99.94％-107.30％and 99.65％-106.43％,all within the range of 80.00％-125.00％.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.

Objective To evaluate tolerability,safety and pharmacokinetics of JS026 and JS026-JS016 single dose intravenous infusion in healthy adults.Methods This phase 1,randomized,double-blind,placebo-controlled,dose-escalation study totally included 48 participants:32 healthy subjects were enrolled in JS026 single intravenous infusion groups and 16 healthy subjects were enrolled in JS026-JS016 groups.JS026 was sequentially administered from low dose to high dose(30-1 000 mg),with intravenous infusion of JS026 or placebo in JS026 single-dose groups,and intravenous infusion of JS026-JS016 or placebo in the combination drug groups.Blood was collected according to the time point designed for trial.Serum concentrations of JS026 and JS016 were determined by enzyme linked immunosorbnent assay(ELISA),and pharmacokinetics parameters were calculated by WinNonlin 8.2.The power model method was used to evaluate the linear analysis of dose and drug exposure.Results 47 subjects completed trial and 1 subject lost to follow-up.After a single intravenous injection of JS026 of 30 mg,100 mg,300 mg,600 mg,and 1 000 mg,mean Cmax were(9.47±1.53),(33.20±4.95),(96.10±13.70),(177.00±22.20)and(353.00±56.70)μg·mL-1,respectively;mean AUC0-∞ were(4 225.00±607.00),(1.78 × 104±3 268.00),(5.83 × 104±1 038.00),(1.07 × 105±152.00),(1.66 × 105±327.00)μg·h·mL-1,respectively;mean t1/2 of JS026 were 563-709 h.The Cmax and AUC0-∞ of JS026 were basically similar alone or in combination with JS016.The results of Power model showed that Cmax and AUC0-∞ increased approximately linearly with the increasing dose of JS026.Treatment emergent adverse event was not increasing when dose increased and most of adverse event associated with drugs were abnormal on laboratory tests and haematuria,thus JS026 and JS016 was well tolerated in all groups.Conclusion The single intravenous infusion of JS026 can almost be thought to be a linear relationship between the doses and drug serum exposure.JS016 had no significant effect on serum concentration of JS026 and JS026 was well tolerated and safe in healthy subjects within 30-1 000 mg.