Gambogic acid, a caged xanthone compound derived from Garcinia, has been proven to be an important substance basis for the pharmacological effects of the plant. In recent years, it has received continuous attention due to its broad and significant pharmacological activities. Modern pharmacological investigations have demonstrated that gambogic acid endows various therapeutic effects such as anti-inflammatory, antioxidant, and anti-tumor activities, as well as benefits in retinopathy, organ protection, anti-microbial infection, bone protection, and neuropathic pain relief. Nevertheless, there is currently a lack of systematic summary and integration of the pharmacological effects and mechanisms of gambogic acid, which is critical for advancing the clinical application of this natural product. In addition, current research has raised concerns about potential safety risks associated with gambogic acid, such as organ toxicity, developmental toxicity, and hemolysis. Given this, this paper systematically reviewed and summarized the pharmacological effects, mechanisms, and toxicological profiles of gambogic acid, aiming to provide reference and data support for its clinical translation.
Xanthones/toxicity* ; Humans ; Animals ; Drugs, Chinese Herbal/toxicity* ; Garcinia/chemistry*

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

Acute Disease ; Aged ; Anti-Bacterial Agents/therapeutic use* ; Bacteremia/microbiology* ; Female ; Hepatitis B, Chronic/complications* ; Hepatitis C, Chronic/complications* ; Humans ; Hypersplenism/complications* ; Liver Cirrhosis/complications* ; Meningococcal Infections/microbiology* ; Neisseria meningitidis/isolation & purification* ; Peritonitis/microbiology*

BACKGROUND: The significant morbidity and mortality resulted from the infection of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for urgent development of effective and safe vaccines. We report the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, KCONVAC, in healthy adults. METHODS: Phase 1 and phase 2 randomized, double-blind, and placebo-controlled trials of KCONVAC were conducted in healthy Chinese adults aged 18 to 59 years. The participants in the phase 1 trial were randomized to receive two doses, one each on Days 0 and 14, of either KCONVAC (5 or 10 μg/dose) or placebo. The participants in the phase 2 trial were randomized to receive either KCONVAC (at 5 or 10 μg/dose) or placebo on Days 0 and 14 (0/14 regimen) or Days 0 and 28 (0/28 regimen). In the phase 1 trial, the primary safety endpoint was the proportion of participants experiencing adverse reactions/events within 28 days following the administration of each dose. In the phase 2 trial, the primary immunogenicity endpoints were neutralization antibody seroconversion and titer and anti-receptor-binding domain immunoglobulin G seroconversion at 28 days after the second dose. RESULTS: In the phase 1 trial, 60 participants were enrolled and received at least one dose of 5-μg vaccine (n = 24), 10-μg vaccine (n = 24), or placebo (n = 12). In the phase 2 trial, 500 participants were enrolled and received at least one dose of 5-μg vaccine (n = 100 for 0/14 or 0/28 regimens), 10-μg vaccine (n = 100 for each regimen), or placebo (n = 50 for each regimen). In the phase 1 trial, 13 (54%), 11 (46%), and seven (7/12) participants reported at least one adverse event (AE) after receiving 5-, 10-μg vaccine, or placebo, respectively. In the phase 2 trial, 16 (16%), 19 (19%), and nine (18%) 0/14-regimen participants reported at least one AE after receiving 5-, 10-μg vaccine, or placebo, respectively. Similar AE incidences were observed in the three 0/28-regimen treatment groups. No AEs with an intensity of grade 3+ were reported, expect for one vaccine-unrelated serious AE (foot fracture) reported in the phase 1 trial. KCONVAC induced significant antibody responses; 0/28 regimen showed a higher immune responses than that did 0/14 regimen after receiving two vaccine doses. CONCLUSIONS: Both doses of KCONVAC are well tolerated and able to induce robust immune responses in healthy adults. These results support testing 5-μg vaccine in the 0/28 regimen in an upcoming phase 3 efficacy trial. TRIAL REGISTRATION http://www.chictr.org.cn/index.aspx (No. ChiCTR2000038804, http://www.chictr.org.cn/showproj.aspx?proj=62350; No. ChiCTR2000039462, http://www.chictr.org.cn/showproj.aspx?proj=63353).
Adult ; COVID-19 ; COVID-19 Vaccines ; Double-Blind Method ; Humans ; SARS-CoV-2 ; Vaccines, Inactivated/adverse effects*

BACKGROUND: Despite the recent large number of studies comparing endoscopic and laparoscopic resection for small gastrointestinal stromal tumors (GISTs) (diameter ≤ 5 cm), the results remain conflicting. The objective of this work was to perform a cumulative meta-analysis to assess the advantages and disadvantages of endoscopic resection vs. laparoscopic resection. METHODS: The meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched medical databases up to January 2020. Meta-analytical random or fixed effects models were used in pooled analyses. Meta-regression, cumulative meta-analyses, and subgroup analyses were performed to improve the accuracy of the conclusion. Sensitivity analyses were applied to assess the robustness of the results. RESULTS: A total of 12 cohort studies with 1383 participants comparing endoscopic resection and laparoscopic resection were identified, while three cohort studies with 167 participants comparing endoscopic resection and laparoscopic and endoscopic cooperative surgery were found. We found that endoscopic resection had shorter operation times (weighted mean difference [WMD] = -27.1 min, 95% confidence interval [CI]: -40.8 min to -13.4 min) and lengths of hospital stay (WMD = -1.43 d, 95% CI: -2.31 d to -0.56 d) than did laparoscopic resection. The results were stable and reliable. There were no significant differences in terms of blood loss, hospitalization costs, incidence of complications or recurrence rates. For tumor sizes 2 - 5 cm, endoscopic resection increased the risk of positive margins (relative risk [RR] = 5.78, 95% CI: 1.31 - 25.46). Although operation times for endoscopic resection were shorter than those of laparoscopic and endoscopic cooperative surgery (WMD = -41.03 min, 95% CI: -59.53 min to -22.54 min), there was a higher incidence of complications (RR = 4.03, 95% CI: 1.57 - 10.34). CONCLUSIONS In general, endoscopic resection is an alternative method for gastric GISTs ≤ 5 cm. Laparoscopic and endoscopic cooperative surgery may work well in combination. Further randomized controlled trials are recommended to validate or update these results.
Gastrectomy ; Gastrointestinal Stromal Tumors/surgery* ; Humans ; Laparoscopy ; Length of Stay ; Neoplasm Recurrence, Local/surgery* ; Postoperative Complications ; Stomach Neoplasms/surgery* ; Treatment Outcome

Objective To investigate the risk factors of perioperative complications of laparoscopic radical distal gastrectomy and influence of body shape on the short-term therapeutic effects.Methods The retrospective case-control study was conducted.The clinicopathological data of 506 patients (328 males and 178 females,average age 60 years with the range of 24-85 years) who underwent laparoscopic radical distal gastrectomy+D2 lymph nodes dissection in the 8 clinical centers between March 2016 and November 2018 were collected,including 143 in the First Affiliated Hospital of Xiamen University,66 in the Affiliated Hospital of Qinghai University,66 in the Second Affiliated Hospital of Wenzhou Medical University,64 in the Zhongshan Hospital of Xiamen University,54 in the Affiliated Hangzhou First people's Hospital of Zhejiang University School of Medicine,48 in the Zhangzhou Affiliated Hospital of Fujian Medical University,35 in the Affiliated Quanzhou First Hospital of Fujian Medical University,30 in the Second Affiliated Hospital of Xiamen Medical College.The maximum thickness of subcutaneous fat at the level of umbilicus (USCF),the maximum vertical distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UAPD),the maximum horizontal distance between the anterior abdominal skin and the back skin at the level of the umbilicus (UTD),the maximum verticaldistance between the anterior abdominal skin and the back skin at the level of the xiphoid bone (XAPD),the maximum horizontal distance between the.anterior abdominal skin and the back skin at the level of the xiphoid bone (XTD),the distance between the anterior abdominal skin and the root of celiac artery (CAD) and the maximum horizontal distance at a right angle to CAD (CATD) were measured using preoperative imaging examinations.Observation indicators:(1) intraoperative and postoperative situations;(2) follow-up situations;(3) risk factors analysis of perioperative complications;(4) influence of body shape related indexes on intraoperative situations and postoperative recovery:① Pearson univariate correlation analysis,② liner regression model analysis.Followup using outpatient examination and telephone interview was performed to detect the postoperative survival and tumor recurrence or metastasis up to December 2018.Measurement data with normal distribution were represented as Mean±SD.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using the chi-square test.Comparisons of ordinal data were analyzed by Mann-Whitney U nonparametric test.Risk factors of perioperative complications of laparoscopic distal gastrectomy were analyzed by Logistic regression model.Influence of body shape related indexes on intraoperative situations and postoperative recovery was analyzed by Pearson univariate correlation analysis and liner regression model.Results (1) Intraoperative and postoperative situations:all the 506 patients underwent successful laparoscopic distal gastrectomy,including 103 with Billroth Ⅰ anastomosis,140 with Billroth Ⅱ anastomosis,201 with Billroth Ⅱ + Braun anastomosis,62 with Roux-en-Y anastomosis.The operation time,volume of intraoperative blood loss,number of lymph nodes dissected,time to postoperative anal exsufflation,time for initial fluid diet intake,time for initial semi-fluid diet intake and duration of postoperative hospital stay were (233±44)minutes,(102±86)mL,34±13,(3.6±1.5)days,(5.8±3.3)days,(8.3±3.8)days,(12.2±5.7)days respectively in the 506 patients.Of 506 patients,196 were defined as pathological stage Ⅰ,122 were defined as pathological stage Ⅱ and 188 were defined as pathological stage Ⅲ postoperatively.Of 506 patients,93 had 106 times of perioperative complications,including 33 times of pulmonary and upper respiratory infection,12 times of incisional infection,11 times of anastomotic leakage,11 times of abdominal infection,8 times of intestinal obstruction,8 times of gastroplegia,6 times of abdominal hemorrhage,5 times of bacteremia,3 times of anastomotic hemorrhage,3 times of lymph fluid leakage,2 times of pancreatic leakage,1 time of urinary infection,1 time of anatomotic stenosis,1 time of deep venous thrombosis and 1 time of pulmonary embolism;the same patient can merge multiple complications.Eleven patients were in the Clavien-Dindo classification ≥ Ⅲ.(2) Follow-up situations:465 of 506 patients were followed up for 1-32 months with a median time of 12 months.During the follow-up,451 had postoperative survival and 38 had tumor recurrence or metastasis.(3) Risk factors analysis of perioperative complications.① Results of univariate analysis showed that age,body mass index (BMI),preoperative hemoglobin,preoperative serum albumin and XAPD were related factors affecting perioperative complications of laparoscopic distal gastrectomy (x2 =10.289,7.427,5.269,5.481,4.285,P＜ 0.05).② Results of multivariate analysis showed that age,BMI,preoperative serum albumin were independent related factors affecting perioperative complications of laparoscopic distal gastrectomy (odds ratio =1.033,1.118,0.937,95％ interval confidence:1.011-1.057,1.025-1.219,0.887-0.990,P＜0.05).(4) Influence of body shape related indexes on intraoperative situations and postoperative recovery.① Results of Pearson univariate correlation analysis showed correlations between UAPD,XAPD,CAD,CATD and volume of intraoperative blood loss (r=0.107,0.169,0.179,0.106,P＜0.05),between UAPD,XAPD,CAD and the number of lymph nodes dissected (r=-0.137,-0.143,-0.173,P＜0.05),between USCF,XAPD and time to postoperative anal exsufflation (r =0.122,0.109,P＜0.05),between USCF,XAPD,CAD and time for initial fluid diet intake (r=0.132,0.108,0.132,P＜0.05),between USCF,XAPD and duration of postoperative hospital stay (r=0.116,0.100,P＜0.05).② Results of liner regression model analysis showed a positive correlation between CAD and volume of intraoperative blood loss (r =6.776),a negative correlation between CAD and the number of lymph nodes dissected (r =-0.841),with statistically significant differences (t =2.410,-1.992,P＜ 0.05);a positive correlation between USCF and time to postoperative anal exsufflation (r=0.170),between USCF and time for initial fluid diet intake (r=0.365),between USCF and duration of postoperative hospital stay (r=0.636) respectively,with statisticallysignificant differences (t =2.188,1.981,2.107,P＜ 0.05).Conclusions Abdominal shape can influence intraoperative situations and postoperative recovery of laparoscopic distal gastrectomy,but cannot increase risks ofperioperative complications.Age,BMI and preoperative serum albumin are independent related factors affecting perioperative complications of laparoscopic distal gastrectomy.

Objective: To observe the effect of modified Chaihu Shugantang on the expression of miRNA-204 in hippocampus of epileptic mice, and to explore its mechanism of neuroprotection. Method: The sixty mice were randomly divided into 6 groups:normal group, model group (pilocarpine 180 mg·kg^-1), and modified Chaihu Shugantang group (7 g·kg^-1·d^-1), modified Chaihu Shugantang+miRNA-204 mimic group (7 g·kg^-1·d^-1+ 2 μL), modified Chaihu Shugantang+miRNA-204 inhibitor group (7 g·kg^-1·d^-1+2 μL), carbamazepine group (30 mg·kg^-1·d^-1),each was given intragastric administration for 2 weeks,using pilocarpine to cause epilepsy in mice, respectively, add flavor to Bupleurum after intragastric administration, inhibition and overexpression of miRNA-204, the mice were sacrificed and their hippocampus tissues were harvested.The indicators of each group were observed, Real-time quantitative PCR detecting system (Real-time PCR) was used to detect mouse hippocampal miRNA-204 expression, Western blot analysis of autophagy-related protein microtubule-associated protein light chain 3 (LC3), autophagy-associated marker protein 7 (ATG7) expression, hematoxylin pathological condition of hippocampus in each group was observed by hematoxylin-eosin(HE)staining.The autophagy of hippocampus in each group was observed by transmission electron microscopy. Result: Compared with normal group, the expression of miRNA-204 was significantly decreased in model group (P<0.01), the pathological changes in the hippocampal C1 area were the most obvious, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was increased (P<0.01), and the autophagy was small. Compared with model group, the expression of miRNA-204 in the hippocampus of the modified Chaihu Shugantang group was increased (P<0.05), the pathological changes in the hippocampal C1 area were alleviated, the expression of ATG7, LC3Ⅱ/LC3Ⅰ was decreased (P<0.05), and the autophagy was small. The number of body decreased,the expression of miRNA-204 in hippocampus of modified Chaihu Shugantang+miRNA-204 mimic group was significantly increased (P<0.01), the pathological changes in hippocampal C1 area were the lightest, and the expression of ATG7, LC3Ⅱ/LC3I was decreased (P<0.01), the number of autophagosomes was the least.Compared with modified Chaihu Shugantang group, the above-mentioned indicators of modified Chaihu Shugantang+miRNA-204 inhibitor group had the same change trend and the change range decreased (P<0.05). Conclusion: Modified Chaihu Shugantang can improve the pathological changes of hippocampus in mice with epilepsy and play a neuroprotective role. The mechanism may be to increase the expression of miRNA-204 in hippocampus of mice with epilepsy, inhibit excessive autophagy of neurons and reduce apoptosis.

Objective:To study HPLC fingerprints of Achyranthis Bidentatae Radix from different origins,compare different specifications in the same origin,and explore the effect of origin and specifications on the quality of Achyranthis Bidentatae Radix and relationship between the specifications and the internal quality of Achyranthis Bidentatae Radix, in order to provide basis for the identification of its origin. Method:The HPLC fingerprints of Achyranthis Bidentatae Radix from different origins and with different specifications in the same origin were collected. The similarity analysis,cluster analysis and principal component analysis were adopted to analyze the fingerprints,the differences in fingerprints of Achyranthis Bidentatae Radix from different origins and with different specifications in the same origin were compared. Result:Analysis of different origins and principal component analysis could be used to distinguish Achyranthis Bidentatae Radix from five producing areas,and the identification results of origin analysis was better than those of cluster analysis and similarity analysis. Analysis of different specifications, similarity analysis or principal component analysis could not distinguish Achyranthis Bidentatae Radix with different specifications. Conclusion:There are significant differences in chemical composition and peak height among Achyranthis Bidentatae Radix from different origins,with less differences in chemical composition and peak height of Achyranthis Bidentatae Radix with different specifications, the principal component analysis could be used to identify origins of Achyranthis Bidentatae Radix.

OBJECTIVE: To explore the application value and clinical effect of three-dimensional printing combined with composite plate internal fixation in the treatment of old acetabular posterior wall fracture. METHODS: From May 2010 to October 2016, Mimics 19.0 software was used to plan preoperatively according to a 1:1 print pelvic 3D model. At the same time, 23 patients with old acetabular posterior wall fractures were treated with combined plate internal fixation, including 15 males and 8 females, aged 20 to 63 (43.0±5.1) years old, and the time from injury to operation was 23 to 101(47.0±10.5) days. According to Letournel-Judet classification, 11 cases were posterior wall fracture, 7 cases were transverse with posterior wall fracture, and 5 cases were posterior column with posterior wall fracture. All patients were treated with single Kocher-Langenbeck approach combined plate internal fixation, and the evaluation indexes were recorded during operation, after operation and during follow-up. RESULTS: The operation time of 23 patients was (113.5±11.5) min, bleeding was (550.0±104.7) ml and fluoroscopy was (12.7±0.8) s. Matta radiographic reduction criteria were used: excellent in 14 cases, good in 7 cases and poor in 2 cases; 23 patients were followed up for 10 to 24 (16.0±5.6) months. The hip function was evaluated according to the modified Merle d'Aubingne and Postal scoring system at the last follow-up: excellent in 11 cases, good in 8 cases, fair in 3 cases and poor in 1 case. There were 3 cases of traumatic arthritis, 1 case of femoral head necrosis, 2 cases of heterotopic ossification and 5 cases of sciatic nerve irritation. CONCLUSIONS 3D printing technique is an effective and fast method for the treatment of old acetabular posterior wall fractures. In addition, the printing model can provide three-dimensional morphological structure for the operator, combined with preoperative simulation, facilitate intraoperative reduction, and effectively improve the efficiency of surgery.
Acetabulum ; Adolescent ; Adult ; Aged ; Bone Plates ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; Humans ; Male ; Printing, Three-Dimensional ; Treatment Outcome ; Young Adult

Objective:To investigate and compare the fingerprints of different polarity fractions (petroleumether,chloroform,ethyl acetate,n-butanol,water) of fresh Gardeniae Fructus with different fruit shapes,and further understand the content difference and distribution of its chemical composition. Method:Gardeniae Fructus was reflux extracted by water in order to obtain the water extract; water extract 0.1 g and dissolved with 50 mL water,then it was extracted by petroleum ether,chloroform,ethyl acetate and n-butanol in turn in order to obtain the different extraction phases and the water phase. Each phase was condensed to extractum. Finally,the samples were analyzed by high performance liquid chromatography (HPLC) fingerprints and the similarity evaluation software was used for data analysis. Result:Fingerprint of chloroform fraction of water extract in gardenia from different habitats can be used to distinguish Gardeniae Fructus from Fujian,Henan and Jiangxi. The differences between the water extract of Gardeniae Fructus from Fujian and those of Henan and Jiangxi were mainly manifested in the petroleum ether fraction, and the fat-soluble components of Gardeniae Fructus were more than those of Henan and Jiangxi. The differences between the water extract of Gardeniae Fructus from Henan and those of Fujian and Jiangxi were mainly manifested in the ethyl acetate fraction,and the content of iridoid glycosides was significantly higher than that in Fujian and Henan. The differences between the water extract of gardenia from Jiangxi and those of Fujian and Henan were mainly manifested in the n-butanol fraction,organic acid peak C1 not detected. The fingerprint of chloroform fraction of water extract in Gardeniae Fructus can be used to distinguish Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs from Fujian and Henan,and the contents of all components of Gardeniae Fructus of seven ribs were more than those in Gardeniae Fructus of six ribs. The fingerprint of petroleum ether fraction of water extract in Gardeniae Fructus can be used to distinguish Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs from Jiangxi. The Z3 peak of Gardeniae Fructus of six ribs from Henan was obviously higher than that of Gardeniae Fructus of seven ribs. The contents of all components on chloroform and ethyl acetate fractions of water extract in Gardeniae Fructus of seven ribs were significantly higher than those of Gardeniae Fructus of six ribs. Conclusion:There are significant differences on chemical constituents and content among Gardeniae Fructus from Fujian,Henan and Jiangxi. The main difference of fingerprint between Gardeniae Fructus of six ribs and Gardeniae Fructus of seven ribs is the peak height.