ObjectiveTo explore the effect and mechanism of Jianpi Xiaoai prescription （JPXA） in ameliorating the 5-fluorouracil （5-FU） resistance of colon cancer. MethodsA HCT116/5-FU resistant cell line was established. Different concentrations （10%， 15%， 20%） of JPXA-containing serum and drug-free serum were used for intervention， and 10% fetal bovine serum （10% FBS）， fibroblast growth factor receptor （FGFR） inhibitor （AZD4547）， and recombinant fibroblast growth factor 2 （FGF2） were set as the control groups. Sensitive HCT116 cells were used in the FGF2 group， while HCT116/5-FU cells were used in other groups. Drug resistance， the level of FGF2 in the cell culture medium， the mRNA level of FGF2 in cells， and the protein levels of FGF2/FGFR and phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） were determined. The drug-resistant cells were transplanted into the axilla of nude mice to establish a tumor model. The modeled mice were allocated into model， JPXA （15 g·kg^-1）， 5-FU （0.02 g·kg^-1）， JPXA+5-FU （15 g·kg^-1+0.02 g·kg^-1）， AZD4547 （0.012 5 g·kg^-1）， and AZD4547+5-FU （0.012 5 g·kg^-1+0.02 g·kg^-1） groups. The tumor growth and the protein levels of FGF/FGFR and PI3K/Akt in each group were observed. ResultsThe survival rate of HCT116/5-FU cells decreased in all the JPXA groups with different concentrations. The cell survival rate was decreased most obviously in the 20% JPXA group. The level of FGF2 in the cell culture medium and the mRNA level of FGF2 in cells of each JXPA group decreased， and the decrease was the most significant in the 20% group （P<0.01）. HCT116/5-FU cells showed up-regulated protein levels of FGF2 and phosphorylated fibroblast growth factor receptor 1 （p-FGFR1）， but down-regulated protein level of FGFR1 （P<0.01）. JPXA down-regulated the expression of FGF2 and p-FGFR1 and up-regulated the expression of FGFR1 （P<0.05）. In addition， JPXA down-regulated the expression levels of phosphorylated protein kinase B （p-Akt） and phosphorylated mammalian target of rapamycin （p-mTOR）， while up-regulating the expression levels of Akt and Bcl-2-asociated death promoter （Bad） （P<0.05）. Animal experiments showed that the JPXA combined with 5-FU significantly inhibited the growth of drug-resistant tumors， reduced the protein levels of FGF2， p-FGFR1， phosphorylated phosphatidylinositol-3-kinase （p-PI3K）， p-Akt， and p-mTOR， and increased the expression of Bad. It indicated that JPXA can inhibit the FGF2/FGFR1 signaling in colon cancer and regulate PI3K/Akt and downstream signaling pathways. ConclusionJPXA can ameliorate the chemotherapy resistance of colon cancer through down-regulating FGF2 expression and inhibiting the activation of the PI3K/Akt signaling pathway.

Objective:To evaluate the efficacy and safety of transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for erythematotelangiectatic rosacea (ETR).Methods:This was a randomized controlled trial conducted from March to October 2024. At Sichuan Provincial People′s Hospital, 60 patients with newly diagnosed ETR were prospectively enrolled and randomized by a random number table into study group [ n=30; 6 male and 24 female; aged 18-60 (38.9±9.8) years] and control group [ n=30; 4 male and 26 female; aged 18-60 (35.7±10.1) years]. The study group received transdermal delivery of compound glycyrrhizin injection by a medium-frequency drug-delivery therapeutic apparatus together with oral azithromycin and hydroxychloroquine sulfate, whereas the control group received oral azithromycin and hydroxychloroquine sulfate. The efficacy evaluations were conducted at baseline and at weeks 2, 4, 6, and 8 post-treatment. Outcome measures included percentage of erythema area, stratum corneum hydration, transepidermal water loss (TEWL), clinician′s erythema assessment (CEA), erythema and telangiectasia scores, dermatology life quality index (DLQI), and efficacy rate. Adverse reactions during treatment were also recorded. Results:Compared with baseline, both groups exhibited significant reductions in percentage of erythema area, TEWL, CEA, erythema and telangiectasia score, and DLQI, and significant increases in stratum corneum hydration at each post-treatment time point (all P<0.05). After 2, 4, 6, and 8 weeks of treatment, the percentage of erythema area, erythema and telangiectasia scores in the study group were all lower than those in the control group, while the stratum corneum hydration level in the study group was higher than that in the control group (all P<0.05). After 4, 6, and 8 weeks of treatment, TEWL, CEA, and DLQI in the study group were all lower than those in the control group (all P<0.05). After 4 weeks of treatment, the efficacy rate in the study group was 56.7% (17/30), which was higher than that of the control group at 23.3% (7/30, P=0.046). After 6 weeks of treatment, the efficacy rate in the study group was 83.3% (25/30), higher than that of the control group at 50.0% (15/30, P=0.020). After 8 weeks of treatment, the efficacy rate in the study group was 86.7% (26/30), higher than that of the control group at 66.7% (20/30, P<0.001). No severe adverse reactions were observed in either group. Conclusion:Transdermal delivery of compound glycyrrhizin injection as an adjunctive treatment for ETR demonstrates favorable efficacy and good safety.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Based on the high-fat diet-induced hyperlipidemia rat model, this study aimed to evaluate the lipid-lowering effect of Arisaema Cum Bile and explore its mechanisms, providing experimental evidence for its clinical application. Biochemical analysis was used to detect serum levels of alanine aminotransferase(ALT), aspartate aminotransferase(AST), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), triglycerides(TG), and total cholesterol(TC) to assess the lipid-lowering activity of Arisaema Cum Bile. Additionally, 16S rDNA sequencing and metabolomics techniques were employed to jointly elucidate the lipid-lowering mechanisms of Arisaema Cum Bile. The experimental results showed that high-dose Arisaema Cum Bile(PBA-H) significantly reduced serum ALT, AST, LDL-C, TG, and TC levels(P<0.01), and significantly increased HDL-C levels(P<0.01). The effect was similar to that of fenofibrate, with no significant difference. Furthermore, Arisaema Cum Bile significantly alleviated hepatocyte ballooning and mitigated fatty degeneration in liver tissues. As indicated by 16S rDNA sequencing results, PBA-H significantly enhanced both alpha and beta diversity of the gut microbiota in the model rats, notably increasing the relative abundance of Akkermansia and Subdoligranulum species(P<0.01). Liver metabolomics analysis revealed that PBA-H primarily regulated pathways involved in arachidonic acid metabolism, vitamin B_6 metabolism, and steroid biosynthesis. In summary, Arisaema Cum Bile significantly improved abnormal blood lipid levels and liver pathology induced by a high-fat diet, regulated hepatic metabolic disorders, and improved the abundance and structural composition of gut microbiota, thereby exerting its lipid-lowering effect. The findings of this study provide experimental evidence for the clinical application of Arisaema Cum Bile and the treatment of hyperlipidemia.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Metabolomics ; Hyperlipidemias/microbiology* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Hypolipidemic Agents/pharmacology* ; Liver/metabolism* ; Humans ; Alanine Transaminase/metabolism* ; Triglycerides/metabolism* ; Aspartate Aminotransferases/metabolism*

OBJECTIVES: To investigate the application value of thromboelastography (TEG) in assessing coagulation function in children with severe hemophilia A (HA) after emicizumab (EMI) therapy. METHODS: A retrospective analysis was performed on the activated partial thromboplastin time (APTT) and TEG testing results of 17 children with severe HA before and after EMI treatment at Shenzhen Children's Hospital from January 2023 to July 2024. Correlation analysis was conducted between coagulation factor VIII (FVIII) equivalent activity and reaction time (R value) measured by TEG. RESULTS: After EMI treatment, the mean bleeding rate for children with severe HA was 1.6 events per year, with 15 children (88%) without spontaneous bleeding or joint bleeding. The children with severe HA showed a significant reduction in APTT after EMI treatment (P<0.05), with a significantly shorter APTT than the normal control group (P<0.05). There was no correlation between APTT and FVIII equivalent activity after treatment (P>0.05). After EMI treatment, TEG parameters, including R value, kinetic time, alpha angle (α), maximum amplitude, clot strength, and coagulation index, shifted from a hypocoagulable state before treatment to a nearly normal state after treatment (P<0.05). The R value demonstrated a strong negative correlation with FVIII equivalent activity (r=-0.758, P<0.05). CONCLUSIONS The bleeding condition of children with severe HA can be effectively controlled after EMI treatment. Routine APTT testing cannot reflect true coagulation function, whereas TEG testing is clinically valuable in assessing the coagulation function of children with severe HA undergoing EMI treatment.
Humans ; Thrombelastography ; Hemophilia A/physiopathology* ; Male ; Child ; Antibodies, Bispecific/therapeutic use* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Blood Coagulation/drug effects* ; Child, Preschool ; Retrospective Studies ; Female ; Partial Thromboplastin Time ; Adolescent ; Infant

Objective To observe the efficacy of self-made auxiliary reduction device combined with sinus tarsi approach(STA)in the treatment of Sanders type Ⅱ to Ⅳ calcaneal fractures.Methods A total of 40 patients with Sanders type Ⅱ to Ⅳ calcaneal fractures admitted to our hospital from January to June 2023 were selected and divided into the control group and the observation group by the random number table method,with 20 cases in each group.Patients in the control group underwent surgical treatment with the heel extensile lateral approach(ELA),while patients in the observation group underwent surgical treatment with the auxiliary reduction device combined with STA.The surgical-related indicators,postoperative complications and ankle-foot anatomical indicators of patients in the two groups were compared.The recovery of limb function was evaluated by the American Orthopaedic Foot and Ankle Society(AOFAS)ankle-hindfoot scale and Maryland foot function score.Results There was no statistically significant difference in the operation time,postoperative incision drying time,or duration of postoperative pain between the two groups(P>0.05).The postoperative suture removal time of the patients in the observation group was shorter than that of the control group,and the difference was statistically significant(P<0.05).The incidence of skin edge necrosis of incision and the total incidence of complications of patients in the observation group were significantly lower than those in the control group(P<0.05).The B?hler angle and Gissane angle of patients in both groups increased after surgery compared with those before surgery(P<0.05);there was no statistically significant difference in the B?hler angle or Gissane angle after surgery of patients between the two groups(P>0.05).The AOFAS score1 week after surgery of the patients in the observation group was higher than that in the control group(P<0.05),while there were no statistically significant differences in the AOFAS scores or Maryland scores of patients at other time points between the two groups(P>0.05).Conclusion The use of the auxiliary reduction device in surgical treatment with STA for Sanders type Ⅱ to Ⅳ calcaneal fractures can effectively restore the function of the foot and ankle,with short postoperative suture removal time and low incidence of postoperative complications.

OBJECTIVE: Humans are exposed to complex mixtures of environmental chemicals and other factors that can affect their health. Analysis of these mixture exposures presents several key challenges for environmental epidemiology and risk assessment, including high dimensionality, correlated exposure, and subtle individual effects. METHODS: We proposed a novel statistical approach, the generalized functional linear model (GFLM), to analyze the health effects of exposure mixtures. GFLM treats the effect of mixture exposures as a smooth function by reordering exposures based on specific mechanisms and capturing internal correlations to provide a meaningful estimation and interpretation. The robustness and efficiency was evaluated under various scenarios through extensive simulation studies. RESULTS: We applied the GFLM to two datasets from the National Health and Nutrition Examination Survey (NHANES). In the first application, we examined the effects of 37 nutrients on BMI (2011-2016 cycles). The GFLM identified a significant mixture effect, with fiber and fat emerging as the nutrients with the greatest negative and positive effects on BMI, respectively. For the second application, we investigated the association between four pre- and perfluoroalkyl substances (PFAS) and gout risk (2007-2018 cycles). Unlike traditional methods, the GFLM indicated no significant association, demonstrating its robustness to multicollinearity. CONCLUSION GFLM framework is a powerful tool for mixture exposure analysis, offering improved handling of correlated exposures and interpretable results. It demonstrates robust performance across various scenarios and real-world applications, advancing our understanding of complex environmental exposures and their health impacts on environmental epidemiology and toxicology.
Humans ; Environmental Exposure/analysis* ; Linear Models ; Nutrition Surveys ; Environmental Pollutants ; Body Mass Index

Objective To investigate the clinical characteristics of intestinal obstruction caused by Meckel diverticulum in children,so as to improve the understanding,diagnosis and treatment of this disease.Methods The clinical data of 103 children with intestinal obstruction caused by Meckel diverticulum admitted to Department of General Surgery,Wuhan Children's Hospital,Tongji Medical College,Huazhong University of Science and Technology from Jul.2015 to Jun.2022 were retrospectively analyzed.There were 78 males and 25 females,with an average age of(4.7±2.6)years old(ranged from 4 months to 12 years old).All 103 cases were admitted for abdominal pain,crying,vomiting or abdominal distension with unknown causes.Results Seventy-four children underwent exploratory laparotomy and 29 underwent laparoscopic exploration.During the operation,it was found that Meckel diverticulum combined with the formation of cord oppressed the intestinal tract,resulting in intestinal obstruction in 65 cases;diverticulum perforation and adhesion obstruction in 15 cases;and secondary intussusception leading to obstruction in 23 cases.Twenty-three cases of secondary intussusception underwent manual reduction of intussusception and Meckel diverticulectomy.Thirty-nine cases were complicated with intestinal necrosis,of which 38 cases underwent cord release,necrotic bowel resection,and intestinal anastomosis;1 case underwent necrotic bowel resection and intestinal fistula due to septic shock.Twelve cases underwent cord release and diverticulectomy,14 cases underwent laparoscopic cord release and diverticulectomy,and 15 cases underwent laparoscopic surgery conversion to diverticulectomy.All patients were clinically cured and followed up for more than 1 year,and no anastomotic leakage,wound infection or other complications occurred.Conclusion The formation of cord is the main cause of intestinal obstruction caused by Meckel diverticulum,with atypical early symptoms,lack of specific symptoms,signs and examination methods,leading to a high misdiagnosis rate.It often causes serious complications such as intestinal necrosis and septic shock.For cases of intestinal obstruction with unknown causes,we should be alert to the possibility of intestinal obstruction caused by Meckel diverticulum.

Objective To develop a predictive model for guiding blood transfusion decisions in pediatric patients with traumatic brain injury(TBI)by identifying and analyzing key factors that influence blood transfusion requirements.Methods A retrospective analysis was conducted on the clinical data of 1,535 pediatric patients with TBI admitted to four medical institutions from January 1,2015,to December 31,2022.Patients were divided into two groups:those who received red blood cell transfusions during hospitalization and those who did not.Comparative analyses were performed on demographic,clinical,and laboratory data between these two groups.Logistic regression analysis was used to identify risk factors associated with in-hospital blood transfusion,and a predictive model was developed using a nomogram.The performance of this model was evaluated using a receiver operating characteristic(ROC)curve.Results Significant differences were observed between the blood transfusion and non-blood transfusion groups in terms of baseline demographics,clinical indicators,and laboratory test results(all P<0.05).Patients in the blood transfusion group exhibited significantly higher in-hospital mortality,compli-cation rates,use of mechanical ventilation,ICU admission rates,and length of stay compared to those in the non-blood transfusion group(all P<0.05).Multivariate logistic regression analysis identified heart rate,presence of other fractures,treatment methods,hemoglobin(Hb),platelet count(Plt),activated partial thromboplastin time(APTT),and D-dimer levels as independent risk factors for blood transfusion in TBI patients.The area under the ROC curve for the blood transfusion prediction model,based on these independent risk factors,was 0.95(95%CI:0.94～0.97),indicating excellent predictive accuracy.Calibration and decision curves further validated the robust-ness and reliability of the model's predictive capacity.Conclusions Heart rate,presence of other fractures,treatment methods,Hb,Plt count,APTT,and D-dimer levels serve as independent risk factors for blood transfusion in TBI patients.The prediction model developed based on these factors demonstrates excellent predictive performance,thereby guiding clinicians in making informed blood transfusion decisions and enhancing the success rate of patient outcomes.

Objective To investigate whether curcumin(CUR)can reduce chondrocyte inflammation and cartilage degradation in osteo-arthritis(OA)and the underlying mechanisms.Methods A rat model of OA was established.Rats were randomly divided into a Sham,OA,CUR+OA,and deferoxamine(DFO)+OA groups with 10 mice in each group.Chondrocytes from 5-day-old SD rats were divided into the control,interleukin-1β(IL-1β),CUR+IL-1β,and DFO+IL-1β groups.A CCK-8 assay was performed to assess the effects of CUR on cell viability alone or combined with IL-1β.Toluidine blue staining and alcian blue staining were used to observe the morphological changes of IL-1β-induced chondrocytes.The expression of inflammatory response-related proteins(COX-2 and iNOS),extracellular matrix degradation-related proteins(COL2A and MMP13),and p53,SLC7A11,and GPX4 proteins during ferroptosis were detected by Western blotting.The mitochondrial membrane potential was detected by JC-1 staining.Mitochondrial morphology was observed using transmission electron microscopy.Safranine O-fast green/HE staining was performed on cartilage tissues.Immunohistochemical staining was performed to detect COL2A and SLC7A11 expression levels.Results CUR and DFO were found to reduce IL-1β-induced inflammation,cartilage degradation,and ferroptosis,and restore mitochondrial function in chondrocytes.CUR also reversed IL-1β-induced changes in collagen Ⅱ,p53,SLC7A11,GPX4,MMP13,iNOS,and COX-2 levels.In vivo,intra-articular injection of CUR significantly improved cartilage injury in the OA rat model,and the percentages of COL2A-and SLC7A11-positive cells significantly increased in the CUR+OA and DFO+OA groups.Conclusion CUR inhibits ferroptosis and ameliorates cartilage degeneration in OA through p53 signaling pathway.