ObjectiveTo explore the potential mechanism of Erchen Decoction （二陈汤， ECD） in improving metabolic syndrome （MS） with phlegm syndrome. MethodsForty mice were randomly divided into a blank group of 10 mice and a modeling group of 30 mice. The MS model with phlegm syndrome was induced in the modeling group by high-fat diet. Thirty successfully modeled mice were randomly divided into a model group， a ECD group， and a metformin group， with 10 mice in each group. The ECD group was given 0.4 g/（kg·d） of ECD， while the metformin group was intervened with 11.1 g/（kg·d） of metformin solution， and the blank group and the model group were given 0.02 ml/（g·d） of sterilized drinking water， all by gavage， once daily for 4 weeks. Body weight， abdominal circumfe-rence， body length， Lee's index and food intake were recorded. Blood glucose and blood lipid levels including fasting blood glucose， triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein cholesterol （HDL-C）， and low-density lipoprotein cholesterol （LDL-C） were measured. ELISA was used to detect serum leptin levels， while HE staining was used to observe liver pathological changes. Western Blot and q-PCR were used to detect protein and mRNA expression of hypothalamic leptin receptor （LepR）， pro melanocortin （POMC）， and neuropeptide Y （NPY） in the hypothalamus. Immunofluorescence was used to detect fluorescence expression of POMC and NPY in the hypothalamic arcuate nucleus region. ResultsPathological results showed that the mice in the model group had numerous fat vacuoles in hepatocytes and significant liver fat deposition， while the ECD and metformin groups showed reduced fat vacuoles and less liver fat deposition. Compared to those in the blank group， the mice in the model group mice showed liver fat deposition， increased body weight， abdominal circumference， Lee's index and food intake； fasting blood glucose， TG， TC， LDL-C， and serum leptin levels were elevated， while HDL-C was decreased； the expression of LepR， POMC protein levels and their mRNA expression decreased， while the protein level and mRNA expression of NPY increased； the fluorescence expression of POMC in the arcuate nucleus was reduced， while NPY fluorescence expression increased （P＜0.05 or P＜0.01）. Compared to the model group， the ECD group and metformin group showed significant improvements in the above indicators （P＜0.05 or P＜0.01）. Compared to the ECD group， the metformin group showed a reduction in body weight and NPY fluorescence expression， and an increase in HDL-C levels （P＜0.05 or P＜0.01）. ConclusionECD can downregulate serum leptin levels and improve glucose and lipid metabolism in the MS of phlegm syndrome. Its mechanism of action may be to reduce liver fat deposition and thereafter affect the expression of neuropeptides related to feeding activity in the hypothalamus.

In this work, starting from 4-hydroxycoumarin, three series of 22 coumarin derivatives, among which 8 have not been reported in the literature, were synthesized and their in vitro anti-inflammatory activities and mechanisms of action were preliminarily investigated using mouse macrophage model. The results showed that most of the derivatives could significantly inhibit the production of pro-inflammatory factor NO, with compounds 2e, 2f, 2g, 2h, 2i, 2j, 4e, and 4f showing better anti-inflammatory activity than the positive control drug dexamethasone. Further experiments showed that compounds 2h and 4f significantly inhibited the production of pro-inflammatory factors IL-6, TNF-α and IL-1β in RAW264.7 macrophages, and could, therefore, be used as lead compounds for further studies.

The Healthy China 2030 Plan set the goal of reducing premature deaths from diabetes by 30% by 2030. However, there has been a lack of assessment of premature mortality for diabetes since the action plan was issued. This study used data from the Global Burden of Disease Study 2021, calculated the premature deaths for diabetes by sex, provinces, and subtypes from 1990 to 2021. We explored the temporal trend of premature mortality using the average annual percent change (AAPC) for different sexes, provinces, and subtypes from 1990 to 2021. Furthermore, we predicted premature mortality for diabetes through 2030 for China and its provinces according to the average annual change rate from 2010 to 2021. There was a first slow upward trend in premature mortality for diabetes from 0.5% in 1990 to 0.6% in 2004, and then a decline until 2021 with premature mortality of 0.4%. By 2030, only Fujian (30.3%) will achieve the desired level of reduction, with only seven provinces meeting the target for females and none for males. There is a large range in the degree of decline between inland and coastal regions, showing obvious geographic differences, and there should be a focus on balancing medical resources.
Humans ; China/epidemiology* ; Female ; Male ; Mortality, Premature/trends* ; Diabetes Mellitus/mortality* ; Goals ; Middle Aged ; Adult

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

Background::Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods::This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied.Results::At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%–69%) and 45% (low vs. placebo, 95% CI 26%–64%), with both P values <0.0001. CM310 at both doses also significantly improved the EASI score, Investigator’s Global Assessment score, daily peak pruritus Numerical Rating Scale, AD-affected body surface area, and Dermatology Life Quality Index compared with placebo. CM310 treatment reduced levels of thymus and activation-regulated chemokine, total immunoglobulin E, lactate dehydrogenase, and blood eosinophils. The incidence of treatment-emergent adverse events (TEAEs) was similar among all three groups, with the most common TEAEs reported being upper respiratory tract infection, atopic dermatitis, hyperlipidemia, and hyperuricemia. No severe adverse events were deemed to be attributed to CM310. Conclusion::CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Trial Registration::ClinicalTrials.gov, NCT04805411.

ObjectiveTo investigate whether anti-PD-1 monoclonal antibody can improve the efficacy and safety of cryoablation combined with lenvatinib in the treatment of unresectable hepatocellular carcinoma （HCC）. MethodsA retrospective analysis was performed for 232 patients with unresectable HCC who were treated at The Fifth Medical Center of Chinese PLA General Hospital from January 2018 to December 2022， among whom 128 received cryoablation combined with lenvatinib （double combination） and 104 received cryoablation combined with lenvatinib and anti-PD-1 monoclonal antibody （triple combination）. Propensity score matching was performed at a ratio of 1∶1， and finally there were 86 patients in each group. The two groups were evaluated in terms of objective response rate （ORR）， disease control rate （DCR）， overall survival （OS）， progression-free survival （PFS）， and adverse events （AEs）. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Survival curves were plotted， and the Kaplan-Meier method was used to calculate the survival rate of patients in both groups， while the log-rank test was used for comparison between the two groups. The Cox regression model was used to calculate hazard ratio （HR） and 95% confidence interval （CI） and perform the univariate and multivariate analyses of influencing factors for prognosis. ResultsThe median follow-up time was 28 months， and there were 33 deaths （38.0%） in the triple combination group and 40 deaths （46.0%） in the double combination group. Compared with the double combination group， the triple combination group had significantly higher ORR （35.6% vs 14.5%， P=0.008） and DCR （86.1% vs 64.1%， P=0.003）. OS and PFS in the triple combination group were significantly higher than those in the double combination group （P=0.045 and 0.026）. The univariate and multivariate Cox proportional-hazards regression model analyses showed that treatment regimen （HR=0.60， P=0.038） and alpha-fetoprotein level （HR=2.37， P=0.001） were independent risk factors for OS， and treatment regimen （HR=0.65， P=0.025）， diabetes mellitus （HR=1.94， P=0.005）， whether or not to have received local treatment （HR=0.63， P=0.014）， and distant metastasis （HR=0.58， P=0.009） were independent risk factors for PFS. There was no significant difference in the incidence rate of AEs between the two groups （P>0.05）. ConclusionFor patients with unresectable HCC， the triple combination of cryoablation， lenvatinib， and anti-PD-1 monoclonal antibody significantly improves the treatment outcome and survival of patients compared with the double combination of cryoablation and lenvatinib， without increasing AEs， which provides a clinical basis for optimizing the treatment regimen for unresectable HCC.

OBJECTIVE To investigate the efficacy and safety of hetrombopag combined with low-dose prednison in the treatment of patients with refractory/recurrent primary immune thrombocytopenia(ITP). METHODS A total of 40 patients with ITP who failed to respond to previous treatment or relapsed in the Department of Hematology of Gansu Provincial People’s Hospital From July 2021 to August 2022 were selected. Used randomized controlled trial research methods, according to the treatment plan, they were divided into observation group and control group, with 20 cases in each group. The control group was treated with low-dose prednison alone. The observation group was combined with hetrombopag treatment on this basis. The efficacy and adverse reactions were compared between the two groups. RESULTS Treatment 6 weeks, patients who's proportion of platelet counts(PLT) reached≥50×109·L−1 and ≥30×109·L−1 in observation group were higher than control group with statistically significant differences in both groups[90%(18/20) vs 50%(10/20), P＝0.006; 90%(18/20) vs 65%(13/20), P＝0.130]; The study also indicated a statistically significant difference in favour of observation group compared with control group in the odds of achieving the outcome of a PLT≥50×109·L−1at least once during 6-week treatment[90%(18/20) vs 55%(11/20), P＝0.147], was more than placebo-treated one. The median time of PLT ≥ 50×109·L−1 for the first time within 6 weeks of treatment in the observation group was 3 weeks, which was the same as that in the control group. After 6 weeks of treatment, the median platelet count in the observation group was higher than that in the control group[97.50(58.25−166.75)×109·L−1 vs 45.50(13.25−82.50)×109·L−1 , P<0.05]. The median PLT count in the observation group was higher than that in the control group at week 1−6 after treatment, and the curative effect was significant. The two groups of patients tolerated the regimen well, and the degree of adverse reactions was mild, which improved quickly after symptomatic treatment. CONCLUSION Hetrombopag combined with low-dose prednison has a high effective rate in the treatment of refractory/recurrent ITP, which is better than that of single use, and the adverse reactions are tolerable, so it can be widely used in clinical practice.

Objective:To observe the effects of warm acupuncture on post-stroke cognitive impairment (PSCI) based on the theory of intestinal flora.Methods:A randomized controlled trial was conducted. 60 patients with PSCI in the Department of Acupuncture and Neurology of the First Affiliated Hospital of Xinjiang Medical University from October 2020 to June 2022 were selected as the observation objects, and were divided into 2 groups by random number table, with 30 cases in each group. On the basis of cognitive rehabilitation training, the treatment group was given warm acupuncture treatment, and the control group was given routine acupuncture treatment. 2 groups were treated for 4 weeks as 1 course, and a total of 4 courses were treated. Montreal cognitive assessment (MoCA) was used to assess patients' cognitive function before and after treatment, and mini-mental state examination (MMSE) was used to assess patients' intelligence level. The numbers of bifidobacteria and lactic acid bacteria in fecal samples were calculated, and plasma gamma-aminobutyric acid (GABA) levels were detected by ELISA to evaluate the clinical efficacy.Results:During the study, 1 case was lost in each of the two groups, and finally 29 cases were included in the curative effect statistics. The total effective rate was 79.3% (23/29) in the treatment group and 65.5% (19/29) in the control group, with statistical significance ( χ2=43.39， P<0.05). After treatment, MoCA score [(24.23±1.36) vs. (21.26±1.30), t=3.12] and MMSE score [(25.35±1.24) vs. (21.52±1.22), t=3.25] in the treatment group were higher than those in the control group ( P<0.05); Bifidobacterium [(9.20±1.25) LgCFU/g vs. (7.23±1.21) LgCFU/g, t=2.98], Lactic acid bacteria [(8.24±1.12) LgCFU/g vs. (6.25±1.22) LgCFU/g, t=2.92], and the level of GABA [(283.80±83.54) mmol/L vs. (264.76±61.38) mmol/L, t=10.54] were higher than those in the control group ( P<0.05 or P<0.01). Conclusion:Warm acupuncture and moxibustion can effectively regulate the number of intestinal beneficial bacteria in PSCI patients, increase the level of GABA, promote brain tissue repair and improve cognitive function.

Objective To investigate the expression of disulfidptosis-related genes in hepatocellular carcinoma(HCC)and the prognostic value of disulfidptosis in HCC,to construct a prognostic model,and to analyze its impact on the biological processes of HCC and sorafenib resistance.Methods The TCGA-LIHC database was used to collect the mRNA expression profiles and corresponding clinical data of HCC patients,and the LASSO-Cox regression algorithm was used to construct a four-gene predictive model for prognosis in the TCGA cohort.The external datasets ICGC and GSE14520 were used to validate the prognostic efficacy of the model,and the Cancer Drug Sensitivity Genomics(GDSC)data were used to investigate the value of the disulfidptosis model in predicting sorafenib treatment response,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analyses were used to investigate the biological functions of disulfidptosis-related genes.The independent-samples t test was used for comparison of continuous data between two groups,and the chi-square test was used for comparison of categorical data between two groups.The Kaplan-Meier curve and the log-rank test were used to evaluate the difference in prognosis,and univariate and multivariate Cox regression analyses were used to investigate whether risk score was an independent influencing factor for patient prognosis.Results The univariate Cox regression analysis in the TCGA cohort showed that seven known disulfidptosis-related genes were significantly associated with overall survival(OS)in HCC(all P<0.05).The LASSO-Cox regression analysis was used to construct a prognostic model based on disulfidptosis-related genes(DRG),and the risk score RS-DRG was calculated as RS-DRG=(0.061 6)×GYS1 expression level+(0.152 8)×LRPPRC expression level+(0.268 3)×RPN1 expression level+(0.183 5)×SLC7A11 expression level.The log-rank test showed that the patients with a high risk score based on the disulfidptosis model had a significantly lower OS than those with a low risk score(P<0.001).Based on the results of the multivariate Cox regression analysis,risk score was an independent predictive factor for OS in both TCGA and ICGC cohorts(TCGA:hazard ratio[HR]=1.869,P=0.002;ICGC:HR=3.469,P=0.004).The Spearman correlation analysis showed that RS-DRG was significantly positively correlated with the infiltration level of various immune cells(including B lymphocytes,CD4+T lymphocytes,neutrophils,macrophages,and dendritic cells)in tumor microenvironment(all P<0.05).The patients in the high-risk score group had a significantly lower IC50 value of sorafenib and were more sensitive to sorafenib(P<0.001).The KEGG/GO enrichment analysis showed that the differentially expressed disulfidptosis-related genes were significantly enriched in various mitosis-related molecular functions.Conclusion This study constructed a novel prognostic model based on disulfidptosis-related genes,which has a potential clinical value in predicting the prognosis of HCC,and targeting disulfidptosis-related genes may provide a promising approach for HCC treatment.

Fibromyalgia syndrome （FMS） is a refractory， chronic non-articular rheumatic disease characterized by widespread pain throughout the body， for which there are no satisfactory therapeutic drugs or options. There are rich Chinese medical therapies， and some non-drug therapies， such as acupuncture， Tai Chi， and Ba-Duan-Jin， have shown satisfactory efficacy and safety and definite advantages of simultaneously adjusting mind and body. FMS is taken as a disease responding specifically to traditional Chinese medicine （TCM） by the National Administration of Traditional Chinese Medicine in 2018. In order to clarify the research progress in FMS and the clinical advantages of TCM/integrated Chinese and Western medicine， the China Academy of Chinese Medicine organized a seminar for nearly 20 experts in Chinese and Western medicine， including rheumatology， psychology， acupuncture and moxibustion， and encephalopathy， with the topic of difficulties in clinical diagnosis and treatment of FMS and advantages of TCM and Western medicine. The recommendations were reached on the difficulties in early diagnosis and solutions of FMS， mitigation of common non-specific symptoms， preferential analgesic therapy， TCM pathogenesis and treatment advantages， and direction of treatment with integrated Chinese and Western medicine. FMS is currently facing the triple dilemma of low early correct diagnosis， poor patient participation， and unsatisfactory benefit from pure Western medicine treatment. To solve the above problems， this paper suggests that rheumatologists should serve as the main diagnostic force of this disease， and they should improve patient participation in treatment decision-making， implement exercise therapy， and fully utilize the holistic and multidimensional features of TCM， which is effective in alleviating pain， improving mood， and decreasing adverse events. In addition， it is suggested that FMS treatment should rely on both TCM and Western medicine and adopt multidisciplinary joint treatment， which is expected to improve the standard of diagnosis and treatment of FMS in China.