ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Hepatocellular carcinoma(HCC)is one of the most common tumor types and remains a major clinical challenge.Increasing evidence has revealed that mitophagy inhibitors can enhance the effect of chemotherapy on HCC.However,few mitophagy inhibitors have been approved for clinical use in humans.Pyrimethamine(Pyr)is used to treat infections caused by protozoan parasites.Recent studies have reported that Pyr may be beneficial in the treatment of various tumors.However,its mechanism of action is still not clearly defined.Here,we found that blocking mitophagy sensitized cells to Pyr-induced apoptosis.Mechanistically,Pyr potently induced the accumulation of autophagosomes by inhibiting autophagosome-lysosome fusion in human HCC cells.In vitro and in vivo studies revealed that Pyr blocked autophagosome-lysosome fusion by upregulating BNIP3 to inhibit synaptosomal-associated protein 29(SNAP29)-vesicle-associated membrane protein 8(VAMP8)interaction.Moreover,Pyr acted synergistically with sorafenib(Sora)to induce apoptosis and inhibit HCC proliferation in vitro and in vivo.Pyr enhances the sensitivity of HCC cells to Sora,a common chemotherapeutic,by inhibiting mitophagy.Thus,these results provide new insights into the mechanism of action of Pyr and imply that Pyr could potentially be further developed as a novel mitophagy inhibitor.Notably,Pyr and Sora combination therapy could be a promising treatment for malignant HCC.

Objective:To investigate the genetic, clinical, and post-treatment characteristics of patients with glycogen storage disease type Ⅲ (GSD Ⅲ).Methods:A retrospective cohort analysis was performed on the genetic and clinical data of 26 cases with GSD Ⅲ who visited the Children's Hospital affiliated with Fudan University from June 2017 to December 2023. The patients were divided into non-missense variation and missense variation groups according to the types of mutation in the AGL gene.The correlation between genotype and phenotype was analyzed. All patients were treated with uncooked cornstarch after diagnosis. The changes before and after treatment were compared in patients who underwent more than twelve months of follow-up. A P value of <0.05 was used to denote statistical significance. Results:Among the 26 cases enrolled, 13 were female and 13 were male, and the median age of diagnosis was 28 (6 to 134) months. A total of thirty-five different types of AGL gene variation were detected, with c.1735+1G＞T (9/52, 17.3%) as the hotspot variation. The common clinical manifestations were elevated aminotransferases (26/26, 100%), hepatomegaly (25/26, 96.2%), fasting hypoglycemia (25/26, 96.2%), hyperketonemia (16/18, 88.9%), hypertriglyceridemia (TG) (20/26, 76.9%), elevated CK (16/25, 64.0%), and an abnormal electrocardiogram (12/16, 75.0%). Four cases (15.4%) had symptoms of myopathy at diagnosis. Liver biopsy was performed in eighteen cases, among whom 83.3% (15/18) had liver fibrosis≥S2. The number of cases with elevated levels of CK ( P＝0.031) and ALT ( P＝0.038)was pronounced in the non-missense variation group compared to that in the missense variation group. There were no statistically significant differences in age, height, liver size, degree of fibrosis, fasting blood glucose (Glu) and TG ( P>0.05). The median follow-up time of 14 cases was 40.5 (20-73) months, with improvement in body stature, reduced liver size, decreased ALT and TG, and improved Glu. However, four (28.6%) cases had new myopathy symptoms with raised CK ( P<0.05) and with advancing age, increased ALT diminished while CK level elevated ( P<0.05). Conclusions:The common clinical manifestations at the early stage of the GSD Ⅲdiagnosis are elevated aminotransferases, hepatomegaly, fasting hypoglycemia, hyperketonemia, high triglycerides, elevated CK, and fibrotic liver in China. Myopathy symptoms may arise following uncooked cornstarch treatment; however, there is significant improvement in height, liver-related, and metabolic parameters.

Objective To study the impact of a subject's testing state on residual noise level and ABR wave V amplitude during non-sedated ABR testing using Kalman-weighted averaging(KWA).Methods Twenty-one adults(18～34 years old,42 ears)with normal hearing were enrolled for non-sedated ABR testing under three different states(lying,sitting,and writing)in a quiet room using a new Kalman-weighted averaging ABR system(vivosonic integrity system).The residual noise level and the amplitude of wave V for click ABR(cABR)of each subject were recorded.The traditional ABR test system(interacoustics,IA)was also used to record ABR with the residual noise level and the amplitude of wave V measured at the same time.Results ① There was no significant difference in am-plitude of wave V between traditional ABR and non-sedated ABR in three different testing states(P＞0.05).②The residual noise levels in the lying and sitting states of KWA ABR were lower than those of traditional ABR,but there was no statistically difference(P＜0.05).The residual noise level of the KWA ABR system in writing state was significantly higher than that of the other three conditions(P＜0.05).③ There was no significant difference between the left and right ears in the residual noise level and amplitude of wave V for non-sedated ABR in writing state(P＞0.05).Conclusion Compared with traditional ABR,the non-sedated KWA ABR system in uriting state was significantly higher than that of the other three conolitions.Haw ever,the residual noise level in lying and sit-ting states had no significant difference with conditional ABR,and different states of the subject had impact on the residual noise level in the ABR testing to sone extent.

Objective To investigate the distribution of TCM syndromes and syndrome elements of irritable bowel syndrome(IBS);To provide reference for clinical TCM syndrome differentiation and treatment.Methods The patients with IBS who filled in the questionnaire were collected from 18 tertiary Chinese medicine hospitals in China from November 2019 to December 2022,including Xiyuan Hospital,China Academy of Chinese Medical Sciences,Guangdong Provincial Hospital of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine.The contents of questionnaire included the patients'general condition,medical history(onset time,condition changes),Rome Ⅳ symptom diagnostic scale,somatic symptom cluster scale,quality of life scale,hospital anxiety and depression scale,TCM syndromes,etc.The methods of factor analysis and systematic clustering analysis were used,the factors of disease and syndrome were extracted,and the classification of TCM syndrome types was summarized.Results Totally 157 patients were included,87 were male and 70 were female.The age was from 18 to 74 years old.The longest course of disease was 30 years and the shortest was 3 months,with an average of(48.31±5.61)months.Anxiety score:was 3.66±0.30,depression score was 3.39±0.28.The most common TCM symptom was emotional distress(83.4%),followed by diarrhea(80.9%)and abdominal pain(72.6%).The results of factor analysis showed that rotation finally converged after 16 iterations,and 8 common factors and 33 variables were obtained,with a cumulative contribution rate of 60.016%.The sites of IBS were mainly distributed in liver,spleen,large intestine and stomach.The main syndrome factors were qi stagnation,phlegm,dampness,heat and yang deficiency.The results of clustering analysis of 8 common factors showed that the main TCM syndrome types were liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome,and liver-stomach digression syndrome.The main TCM syndrome of diarrhea-predominant IBS was liver stagnation and spleen deficiency syndrome,and the main TCM syndrome of mixed type and constipation type was damp-heat accumulation syndrome.There were statistically significant differences in the distribution of TCM syndrome types in patients with different types(P<0.05).Conclusion The location of IBS is mainly in liver,spleen and large intestine,especially in liver.The TCM syndrome types are mainly liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome.

Referring to ZHANG Xichun's experience in treating dysentery from cold-fire accumulation， the treatment of ulcerative colitis （UC） in this paper can be divided into three stages including cold-fire accumulation stage， excessive heat and putrid intestine stage， and healthy qi deficiency and pathogen lingering stage. For people with slippery and excess pulse in the cold-fire accumulation stage， Xiaochengqi Decoction （小承气汤） added with Baishao （Radix Paeoniae Alba） and Gancao （Radix et Rhizoma Glycyrrhizae） can be used for purgation， while those with deficient pulse， Huazhi Decoction （化滞汤） or Xieli Decoction （燮理汤） can be used. In the excessive heat and putrid intestine stage， Tongbian Baitouweng Decoction （通变白头翁汤） and Jiedu Shenghua Elixir （解毒生化丹） are suggested. In the healthy qi deficiency and pathogen lingering stage， it is advised to use Jiedu Shenghua Elixir added with Shanyao （Rhizoma Dioscoreae）， and Sanbao Porridge （三宝粥）. Additionally， the medication rules， dosage and administration characteristics of Huanglian （Rhizoma Coptidis）-Rougui （Cortex Cinnamomi）， Yadanzi （Fructus Bruceae）， Diyu （Radix Sanguisorbae）， Shanyao and Liuhuang （Sulphur） by ZHANG Xichun have been summarized with the help of modern pharmacological research， so as to provide new ideas for the treatment of UC by TCM.

OBJECTIVE To study the difference of Huangqin decoction combined with Paeoniae Radix Alba(BS) and Paeoniae Radix Rubra(CS)'s effect on ulcerative colitis(UC) based on network pharmacological analysis and animal experiment. METHODS The active constituents of BS and CS were retrieved from TCMSP database and literature, and the potential target was predicted by Swiss Target Prediction. Ulcerative Colitis was used as key words to search disease targets in DisGenet, OMIM, and Genecard databases. The intersection target was obtained by Venny 2.1.0. Cytoscape 3.7.2 software was used to construct network of drug-consumption targets. The STRING platform was used for protein-protein interaction(PPI) network analysis, and Metascape database was applied for GO/WIKI analysis. A dextran sulfate sodium(DSS) induced UC mouse model was established to compare the anti-UC effects of Huangqing decoction combined with BS(HQT-BS) and CS(HQT-CS), respectively. RESULTS There were 7 active components of HQT-BS and 11 active components of HQT-CS in the treatment of ulcerative colitis, respectively, 5 of which were the same. There were 146 and 157 targets respectively, 106 of which were the same. The core targets of HQT-BS were SRC, HSP90AA1, and PIK3R1, while the core targets of HQT-CS were SRC, HSP90AA1, and STAT3. WIKI enrichment analysis showed that several signaling pathways were shared by both BS and CS, such as EGFR tyrosine kinase inhibitor resistance, Notch signaling pathway. EGF/EGFR signaling pathway was the specific pathway related to BS, while Nuclear receptors meta-pathway and Kit receptor signaling pathway were the specific pathways related to CS, respectively. Animal experiments showed that both HQT-BS and HQT-CS could significantly improve colon shortening and tissue pathological alternation induced by DSS. However, HQT-CS was more effective in reducing the expression of interleukin-6 and neurogenic locus notch homolog protein1. CONCLUSION Both HQT-BS and HQT-CS have anti-UC effect, and HQT-CS is the better one.

Background::The disease burdens for endometrial cancer (EC) vary across different countries and geographical regions and change every year. Herein, we reported the updated results of the Global Burden of Disease Study 2019 on EC with respect to age-standardized incidence and mortality from 1990 to 2019.Methods::The annual percentage change (APC) of incidence and mortality was evaluated using joinpoint regression analysis to examine the temporal trends during the same timeframe in terms of the global landscape, different sociodemographic indices (SDI), and geographic regions. The relationship between Human Development Index (HDI) and incidence and mortality was additionally explored.Results::The age-standardized incidence rates (ASIRs) revealed a significant average global elevation by 0.5% per year (95% confidence interval [CI], 0.3–0.7; P <0.001). The age-standardized mortality rates (ASMRs), in contrast, fell by an average of 0.8% per year (95% CI, ?1.0 to ?0.7; P <0.001) worldwide. The ASIRs and ASMRs for EC varied across different SDIs and geographical regions. We noted four temporal trends and a significant reduction by 0.5% per year since 2010 in the ASIR, whereas we detected six consecutively decreasing temporal trends in ASMR during the entire period. Notably, the estimated APCs were significantly positively correlated with HDIs (ρ = 0.22; 95% CI, 0.07–0.35; P = 0.003) with regard to incident cases in 2019. Conclusions::Incidence rates for EC reflected a significant increase overall (although we observed a decline since 2010), and the death rates declined consecutively from 1990 to 2019. We posit that more precise strategies can be tailored and then implemented based on the distinct age-standardized incidence and mortality burden in different geographical areas.

Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

The human gastrointestinal tract is the largest reservoir of bacteria in the body,inhabiting a very complex and active microbial community.Under normal circumstances,the interaction between the intestinal flora and the host maintains a dynamic balance.Spleen deficiency syndrome is a common classic syndrome type in TCM clinical practice.A large number of studies have shown that spleen deficiency syndrome is closely related to intestinal microorganisms,and the balance of intestinal flora is the basis for the normal functioning of the spleen's main transportation and transformation functions.Intestinal flora imbalance can lead to a series of manifestations of spleen deficiency.In addition,intestinal flora is an important medium for the metabolism of polysaccharide components and the effectiveness of traditional Chinese medicine for invigorating the spleen,and traditional Chinese medicine for invigorating the spleen can also play a therapeutic role by regulating the structure and quantity of intestinal flora.This article summarizes the relationship between intestinal flora and spleen deficiency syndrome in physiology,pathology,and the efficacy of traditional Chinese medicine for invigorating the spleen.Based on intestinal flora,the study of spleen deficiency syndrome aims to provide some thoughts and suggestions for revealing the connotation of spleen deficiency syndrome in traditional Chinese medicine.