Objective : To investigate the effects of resveratrol(Res) on fibroblast-like synoviocytes(FLS) in patients with rheumatoid arthritis(RA), and to explore the possible mechanism of Res inhibiting the release of inflammatory factors from FLS. Methods : FLS from RA patients were culturedin vitroand treated with different concentrations of Res(0, 20, 40, 80, 160, 320 μmol/L). The viability of FLS cells was detected by CCK-8 assay after 12 and 24 h. The contents of inflammatory factor interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in cell supernatant were detected by ELISA. The expression levels of cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS) and stimulator of interferon gene(STING) were measured by Western blot; After lentivirus infection with FLS caused the cells to overexpress cGAS, the cells were divided into Control group(blank control), cGAS group(cGAS overexpression), Res+cGAS group(Res 160 μmol/L+cGAS overexpression) and Res group(Res 160 μmol/L). The expression level of STING protein in cells of each group was determined by Western blot, the viability of FLS cells in each group was detected by CCK-8, and the contents of inflammatory factor IL-6 and TNF-α in the supernatant of cells of each group were detected by ELISA method. Results : The results of CCK-8 experiment showed that under 40, 80, 160 μmol/L Res treatment, FLS viability decreased significantly after 24 h compared with blank control group(P<0.01). ELISA results showed that the contents of IL-6 and TNF-α in cell supernatant were also significantly decreased after treatment with Res of 40, 80 and 160 μmol/L(P<0.01). Meanwhile, Western blot results showed that Res could significantly decrease the protein expression levels of STING and cGAS in FLS cells after treatment of 40, 80 and 160 μmol/L(P<0.05,P<0.01). Compared with the Control group, the expression level of STING protein in FLS increased after overexpression of cGAS(P<0.05); compared with the Res group, the content of inflammatory factors in the supernatant of FLS and the expression level of STING protein in FLS significantly increased after overexpression of cGAS(P<0.01,P<0.05). Conclusion The appropriate concentration of Res can inhibit the release of inflammatory cytokines in FLS cells, which may be related to the blocking of cGAS-STING signaling pathway.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

Objective To determine the appropriate time to perform laparoscopic cholecystectomy(LC)for acute calculous cholecystitis.Methods The clinical data of 125 patients with acute calculous cholecystitis who underwent LC between Jan.2018 and Dec.2021 were retrospectively analyzed.According to the interval time from symptom onset to operation,all patients were divided into 2 groups:immediate group(43 cases)who underwent LC within 24 hours and delayed group(82 cases)who underwent LC in 25-72 h.The operation time,intraoperative blood loss,conversion to laparotomy,postoperative complications,postoperative hospitalization days and hospitalization expenses between the two groups were compared.Results The operation time,intraoperative blood loss of immediate group were lower than those of delayed group[50(45,65)min vs 65(55,95)min,10(10,20)ml vs 20(10,30)ml,P＜0.05].There were no significant differences between the two groups with respect to incision infection,bile leak and biliary duct injury(4.7％vs13.4％,2.3％vs 2.4％,2.3％vs 1.2％,P＞0.05),but the total rate of postoperative complications in immediate group reduced significantly(9.3％vs 29.3％,P＜0.05).No mortality occurred in either group.Both of postoperative hospitalization days and direct medical costs reduced in immediate group[5(5,7)d vs 7(6,7)d,6 503(6 231,7 749)yuan vs 7 056(6 448,9 105)yuan,P＜0.05].Conclusion LC for the operable patient with acute calculous cholecystitis,during 24 h from onset of symptom,significantly reduced the operation time,intraoperative blood loss and postoperative hospital stay without increasing the rate of bile leak and biliary duct injury.

Objective:To explore the clinical characteristics of persistent HBeAg positivity in patients with chronic hepatitis B treated with nucleos(t)ide analogues.Methods:A retrospective analysis was performed according to different data types. An independent sample t-test, Mann-Whitney U test, chi-square test, or Fisher's exact probability method were used. Chronic hepatitis B patients followed up for four years were collected from the follow-up case database of the Department of Infectious Diseases of Zhongshan Third Hospital from January 2009 to December 2018 and were divided into two groups, A and B, with 87 and 145 cases respectively, according to the duration of HBeAg-negativity≤ 3 and persistent positivity >3 years. Statistical analysis was conducted on the age, gender, family history, baseline, follow-up visit duration, liver function, and other data among the two patient groups.Results:There were no statistically significant differences in gender, age, family history of liver cirrhosis, family history of liver cancer, liver cirrhosis condition before treatment, fatty liver disease combined condition before treatment, baseline HBsAg, anti-HBc, alanine aminotransferase, albumin, or total bilirubin between the two groups of patients ( P ?>?0.05). HBV DNA and HBeAg were significantly higher in group B than those in group A at baseline, with P≤0.001. Aspartate aminotransferase and γ-glutamyl transferase were significantly higher in group A than those in group B at baseline. The proportion of family history of hepatitis B was significantly higher in group B (69.0%) than that in group A (50.6%) among the two groups of patients, and the difference was statistically significant ( P ?=?0.005). The proportion of mothers with hepatitis B was significantly higher in group B (25.5%) than in group A (11.5%), P ?=?0.010. During the treatment process, the HBV DNA quantification was significantly higher in group B than that in group A at 0.5 and 1 years (P≤0.002). The proportion of HBV DNA <100IU/ml was also significantly different at six months and one year (χ 2=30.327, P ??0.05). Conclusion:HBeAg-positive patients with chronic hepatitis B have persistent HBeAg positivity when treated with long-term nucleos(t)ide analogues. Accordingly, a greater proportion of this kind of patient family and mothers have a remarkable history of hepatitis B and a reduced HBV DNA relapse rate in the early stages (within a year or less).

[Purpose]To analyze the trend of gastric cancer incidence and age characteristics in Jiangsu cancer registration areas from 2009 to 2019.[Methods]Cancer registration data from 2009 to 2019 meeting quality control requirements were collected from 16 cancer registries in Jiangsu Province.The crude incidence rate and age-standardized incidence rate by Chinese standard population in 2000(ASIRC)were calculated by gender,urban/rural areas and age groups.The inci-dence trends were analyzed by Joinpoint.A birth cohort model was constructed to calculate the in-cidence rate of gastric cancer for men and women born between 1929 and 2019.The age composi-tion of gastric cancer incidence in Jiangsu Province between 2009 and 2019 was calculated and compared.[Results]The crude incidence rate and ASIRC of gastric cancer in Jiangsu cancer regi-stration areas from 2009 to 2019 showed a significant decreasing trend in both male and female or urban and rural areas,in which the decrease in male(AAPC=-1.28％,P＜0.001)was higher than that of female(AAPC=-1.17％,P=0.030),and the decrease in urban(AAPC=-1.66％,P＜0.001)was higher than that of rural(AAPC=-0.72％,P＜0.001).The incidence rates of gastric cancer in age groups of 40～79 years old showed a significant decreasing trend from 2009 to 2019 with the AAPC ranging from-6.75％to-3.54％(all P＜0.05).In age groups of 40～79 years old,the inci-dence rates of gastric cancer among people with different years of birth showed a decreasing trend with the increase of the birth year.For ASIRC,the composition of patients aged 60 years old above increased by 0.63％(95％CI:0.46％～0.81％)per year from 2009 to 2019.[Conclusion]The inci-dence rate of gastric cancer in cancer registration areas of Jiangsu Province from 2009 to 2019 showed a decreasing trend,the average age of incidence showed a trend of backward moving,and for age-standardized incidence the proportion of patients over 60 years old was increased.

Objective:To investigate clinical efficacy and safety of venetoclax (VEN)-based regimens in the treatment of acute myeloid leukemia (AML).Methods:The clinical data of 41 AML patients treated with venetoclax-based regimens from January 2021 to December 2021 in Ruijin Hospital North of Shanghai Jiao Tong University School of Medicine were retrospectively analyzed. The treatment regimens included VEN+demethylating drugs ± gene mutation inhibitors or VEN+chemotherapy with a median number of 2 courses (1- 5 courses).Results:The median age of all patients was 60 years (18-73 years), and there were 24 males and 17 females. After 1 course of VEN-based therapy, 22 (53.7%) patients achieved complete remission (CR) or morphological complete remission without complete blood count recovery (CRi), including 5 patients achieving minimal residual disease (MRD) negative. After 2 courses of treatment, of 17 patients available for efficacy evaluation, 7 patients achieved MRD negative. Among 20 relapsed/refractory AML patients, 9 cases achieved CR/CRi after 1 course of treatment, of which 1 patient had MRD negative. Among 21 patients initially treated and re-treated, 13 cases achieved CR/CRi and 1 case achieved partial remission after 1 course of treatment, of which 4 cases had MRD negative.Conclusions:VEN-based treatment regimens for AML have a high remission rate and tolerable adverse effects.

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Based on the unique syndrome characteristics of metabolic associated fatty liver disease （MAFLD） in Lingnan （岭南） area， this paper discussed the clinical experience of Huangqi （Radix Astragali） in the treatment of MAFLD in Lingnan area. It is summarized that spleen deficiency and yang weakness， and internal accumulation of damp-turbidity are the source of the disease， and at the early stage， Huangqi， commonly 15~30 g， could be used to fortify the spleen and warm the earth， thereby making the deficiency fire latent， as well as raise the clear and warm the exterior so as to inhibit damp-turbidity； medication needs to be progressively supplemented， and can be used together with Taizishen （Radix Pseudostellariae）， Baizhu （Rhizoma Atractylodis Macrocephalae）， Fuling （Poria）， and Fangfeng （Radix Saposhnikoviae） to back up the earth and inhibit dampness. Qi stagnation and blood constraint， yin dampness and heat accumulation are the pathogenesis of disease progression. Huangqi should be taken to invigorate the spleen and flourish the liver， unblock yang， and move stagnation. The dosage is often maintained at 30~60 g， to circulate the qi and unblock yang qi in the middle jiao （焦）， usually combined with Chaihu （Radix Bupleuri）， Baishao （Radix Paeoniae Alba） and Yujin （Radix Curcumae） integrating warm and cool medicinals. Stubborn turbid and fat condensing in the liver is a severe stage of the disease and may be concurrent with various pathogens such as dampness， phlegm， and heat， for which 60~90 g Huangqi should be used to invigorate blood and disperse fat， reinforce healthy qi and expel pathogens， often with medicinals that can disperse fat and direct the turbid downward such as Shanzha （Fructus Crataegi）， Juemingzi （Semen Cassiae）， Lulutong （Fructus Liquidambaris） and Zexie （Rhizoma Alismatis）. When prescribing， it is suggested to combine with other medicinals according to the season， thereby adjusting the ascending and descending of the property of Huangqi， thereby conforming to the nature of the four seasons.

Objective:To establish a quantitative detection method for the main components of dust mite allergens Der p 1, Der p 2 specific immunoglobulin E (sIgE) by using the nano-magnetic particle chemiluminescence immunoassay.Methods:The performance indexes of the established method were evaluated after setting up and optimizing the chemiluminescence detection system and immune reaction conditions of sIgE for dust mite allergen. Serum sIgE levels of 50 suspected allergic patients with dust mite were determined by this chemiluminescence method. At the same time, this method was compared with the Phadia kit and the consistency was analyzed by Kappa test. Results:The optimal amount of magnetic beads was 25 μg, the optimal reaction buffer (pH=7.4) contained 0.1 mol/L Tris-HCl and 0.25%( W/ W) casein, the optimal coating solution contatined 20 mmol/L phosphate buffer (PB) and 1%( W/ W) bovine serum albumin (BSA), and the luminescence enhancement solution contained 0.05%( V/ V) Triton X-100. The two-step immunoreaction was adopted, and the detection could be completed with 20 μl sample at the optimal reaction temperature of 37℃. The limit of detection (LOD) of the established nano-magnetic particle chemiluminescence system in detecting Der p 1 and Der p 2 sIgE antibodies were both less than 0.01 kU/L, with the linear range of 0.2-100.0 kU/L, the precision of less than 7%, and the cross contamination rate of 0.19% and 0.21%. Compared with the Phadia system, the positive and negative coincidence rate of Der p 1 were 78.0%(32/41) and 9/9 with good consistency ( Kappa=0.65, P=0.008), and the positive and negative coincidence rate of Der P 2 were 93.3%(28/30) and 85.0%(17/20) with good consistency ( Kappa=0.79, P=0.003). Conclusion:The nano-magnetic particle chemiluminescence immunoassay is successfully established for detecting dust mite allergen sIgE, which has good detection performance and good consistency with Phadia system.

Objective:To investigate the risk factors for intrahepatic cholangiocarcinoma (ICC) after hepatectomy for hepatolithiasis.Methods:The retrospective case-control study was conducted.The clinico-pathological data of 1 071 patients who underwent hepatectomy for hepatolithiasis at the Eastern Hepatobiliary Surgery Hospital of Navy Medical University between January 2010 and December 2011 were collected. There were 379 males and 692 females, aged (53±12)years, with the range of 12-86 years. Patients completed preoperative examinations. For regional hepatolithiasis, the anatomical hepatectomy was performed. For diffused hepatolithiasis, regional damaged lesions which confined to liver segment or lobe were resected. Hepaticolithotomy or cholangio-lithotomy was performed if necessary. When severe stricture of hilar bile duct affects biliary drainage, cholangiojejunostomy or biliary stricture plasty was performed. Observation indicators: (1) preoperative examination, surgical and postoperative situations; (2) follow-up; (3) risk factors analysis of ICC within the 5 years after hepatectomy for hepatolithiasis. Follow-up using outpatient examination and telephone interview was performed to detect the incidence of ICC after hepatectomy up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were described as M (range). Count data were described as absolute numbers or percentages. Continuous variables were converted into categorical variables according to the common clinical values or the best cut-off value of receiver operating characteristic curve. Binary logistic regression model was used for risk factors analysis. The factors with P<0.10 in univariate analysis were included for the multivariate analysis. Results:(1) Preoperative examination, surgical and postoperative situations. Results of preoperative examination: duration of hepatolithiasis-related symptoms of the 1 071 patients was 8.2 years(range, 0-27.0 years), the levels of CA19-9 and CEA were (163±87)U/mL and (5.0±2.1)μg/L, and stones located at left liver, right liver, bilateral sides, common hepatic duct or common bile duct were detected in 545, 245, 228, 53 patients. There were 226 patients complicated with biliary stricture and 172 with segmental atrophy. Of the 1 071 patients, 595 underwent anatomical hepatectomy, 272 underwent regional non-anatomical hepatectomy, 143 underwent cholangiolithotomy, and 61 underwent cholangiojejunostomy. Results of postoperative imaging examination showed residual biliary stricture in 26 patients and residual biliary stones in 74 patients. (2) Follow-up: 1 071 patients were followed up for (8.6±1.5)years. Of the 1 071 patients, 92 developed ICC, with an incidence of 8.590%(92/1 071). There were 32, 66, 90 patients developing ICC within 3, 5, 8 years after hepatectomy, with the incidence of 2.988%(32/1 071), 6.162%(66/1 071), 8.403%(90/1 071). (3) Risk factors analysis of ICC within the 5 years after hepatectomy for hepatolithiasis. The receiver operating characteristic curve of duration of hepatolithiasis-related symptoms for ICC within the 5 years after hepatectomy was constructed, and duration of hepatolithiasis-related symptoms was converted into categorical variable for following analysis using 7 years as the cut-off value based on Youden index. Results of univariate analysis showed that duration of hepatolithiasis-related symptoms>7 years, complication with metabolic diseases, segmental atrophy, postoperative residual stones were related factors for ICC within the 5 years after hepatectomy ( odds ratio=2.939, 2.654, 1.903, 2.361, 95% confidence interval: 1.582-5.460, 1.145-6.154, 1.068-3.390, 1.118-4.987, P<0.05). Results of multivariate analysis based on factors with P<0.10 in the univariate analysis showed that duration of hepatolithiasis-related symptoms>7 years, complication with metabolic diseases, segmental atrophy, postoperative residual stones were independent risk factors for ICC within the 5 years after hepatectomy ( odds ratio=2.843, 2.469, 1.922, 2.202, 95% confidence interval: 1.523-5.309, 1.042-5.851, 1.064-3.472, 1.021-4.747, P<0.05). Conclusions:There was risk of developing ICC after hepatectomy for cholelithiasis. The duration of hepatolithiasis-related symptoms >7 years, complication with metabolic diseases, segmental atrophy and postoperative residual stones are independent risk factors for ICC development within 5 years after hepatectomy.