low transit constipation （STC） is a common functional intestinal disorder caused by impaired colonic transit function， characterized by reduced bowel movement frequency， hard stools， and difficulty in defecation. The mitogen-activated protein kinase （MAPK） signaling pathway， which mainly includes extracellular signal-regulated kinase （ERK）， c-Jun N-terminal kinase （JNK）， and p38 subtypes， plays a critical regulatory role in the occurrence and development of STC. This paper systematically reviews the multiple pathogenic mechanisms of the MAPK signaling pathway in STC and the research progress of traditional Chinese medicine （TCM） intervention.At the mechanistic level， the MAPK signaling pathway promotes the progression of STC through the following links：（1） Activation of p38 upregulates the expression of aquaporin 3 （AQP3）/AQP4 in the colon， leading to excessive reabsorption of water in the intestinal lumen； （2） It forms a positive feedback loop with nuclear factor-κB （NF-κB） to maintain low-grade intestinal inflammation， releases inflammatory factors such as tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and inhibits smooth muscle contraction； （3） Overactivation of p38 downregulates the expression of occludin and mucin 2 while upregulates the expression of claudin-2， thereby disrupting the mucosal barrier； （4） The JNK/p38 signaling pathway activates the caspase cascade to induce apoptosis of intestinal epithelial cells， neurons， and interstitial cells of Cajal； （5） Abnormal ERK signaling and excessive activation of p38/JNK inhibit intestinal smooth muscle contraction and reduce 5-hydroxytryptamine secretion， ultimately resulting in impaired colonic transit function.At the intervention level， TCM compound formulas and single herbs have been proven to improve STC by regulating the MAPK signaling pathway. Their effects are syndrome type-dependent：yin-nourishing formulas （Zengye Chengqi Tang， Tongbian Tang） mainly regulate the ERK/AQP axis； yang-warming formulas （Jichuan Jian） target both ERK/JNK and anti-apoptosis； heat-clearing formulas （Sanren Tang） focus on p38/NF-κB anti-inflammation. A single drug can simultaneously cover multiple aspects including water metabolism， inflammation， barrier function， apoptosis， and intestinal motility.Current relevant studies still have limitations such as mechanisms mostly remaining at the correlational level and a lack of disease-syndrome integrated research models. Future studies should combine specific inhibitors or gene knockout to identify core targets， establish disease-syndrome integrated STC models， and use network pharmacology and molecular docking techniques to deeply analyze the fine mechanism of “component-target-phenotype”， so as to provide high-quality evidence for the precise regulation of the MAPK signaling pathway by TCM in the intervention of STC.

Functional constipation （FC） is a common functional disorder of the intestines， mainly characterized by reduced bowel movement frequency， difficulty in defecation， a sensation of incomplete evacuation， and hard stools， which severely affect patients’ quality of life. Research indicates that the pathogenesis of FC is closely related to gut microbiota dysbiosis and abnormal bile acid secretion. Bile acids， as endogenous natural laxatives， promote bowel movements by enhancing colonic secretion and regulating intestinal motility； meanwhile， gut microbiota influence colonic transit function by regulating the enteric nervous system， immune system， and their metabolic products. Based on an overview of the relationship between gut microbiota and bile acid metabolism， this article systematically reviews the current research status on the mechanisms of traditional Chinese medicine （TCM） in treating FC by regulating the balance of the gut microbiota-bile acid axis. It is found that single Chinese medicinal herbs （such as Atractylodes macrocephala）， isolated compounds （such as Platycodon grandiflorum polysaccharides）， herbal formulas （such as Shanger huang pill）， acupuncture， and moxibustion can up-regulate the abundance of beneficial bacteria， reshape the microbial structure， correct bile acid metabolism， and activate the Takeda G-protein receptor 5/farnesoid X receptor pathway to treat FC.

AIM To evaluate the quality of Gegen Formula Granules.METHODS Linear calibration with two reference substances(LCTRS)was adopted in the predicting of retention time with puerarin and daidzein as internal standards.UPLC characteristic chromatograms were established.The contents of 3'-hydroxy puerarin,puerarin(internal standard),3'-methoxy puerarin,puerarin 6"-O-xyloside,puerarin apioside and daidzin were determined by quantitative determination analysis multi-components by a single marker(QAMS),after which their transfer rates were calculated.RESULTS Compared with relative retention time method,LCTRS demonstrated higher positional accuracy for characteristic peaks and wider application range for columns.There were 9 characteristic peaks in the characteristic chromatograms for 14 batches of formula granules and 15 batches of standard decoctions with the similarities of more than 0.95.The contents and transfer rates of various constituents in formula granules and standard decoctions were basically consistent.CONCLUSION The chemical constituents in formula granules and their standard decoctions of Puerariae lobatae Radix display good consistency,reliable preparation process is observable in the former.

Objectives:To investigate the expression and clinical prognostic implication of secreted frizzled-related protein 4(SFRP4)in the peripheral blood of patients with dilated cardiomyopathy(DCM)and its.Methods:A total of 259 consecutive patients diagnosed with DCM who were admitted to the Cardiac Center of Zhongshan Hospital,Fudan University,from January 2017 to January 2019 were selected for the DCM group.Additionally,84 individuals who underwent health examinations and echocardiography at our hospital during this period,confirmed to be free of cardiovascular diseases,were selected as the control group.Peripheral serum samples were collected from both groups,and serum SFRP4 levels were measured using enzyme-linked immunosorbent assay(ELISA).The correlation between SFRP4 levels and DCM severity,as well as its predictive value for DCM prognosis,were analyzed.Results:Compared to the control group,the serum SFRP4 levels in the DCM group were significantly elevated([28.54±10.25]ng/ml vs.[52.70±19.74]ng/ml,P<0.05).The DCM group was randomly divided into a training set and a validation set in a 2:1 ratio.Multivariate logistic regression analysis in the training set revealed that serum SFRP4 levels were independently associated with all-cause mortality in DCM patients(OR=1.06,95% CI:1.03-1.10,P<0.001).We further evaluated the model's predictive performance with the receiver operating characteristic(ROC)curves(area under curve>0.8),calibration curves,and decision curve analysis,results indicated that the predictive model containing serum SFRP4 levels showed good performance on predicting all-cause mortality in DCM patients.Kaplan-Meier survival curve analysis demonstrated that during a median follow-up of 33.5(11.0,49.0)months,DCM patients with high peripheral blood SFRP4 levels(≥75th percentile)had a significantly higher incidence of all-cause mortality compared to those with low levels(<75th percentile)(28.81% vs.16.57%,P=0.02).Conclusions:The level of SFRP4 in the peripheral blood of DCM patients is significantly elevated,and peripheral serum SFRP4 levels have potential prognostic value for predicting the all-cause mortality in DCM patients.

As global greenhouse gases continue rising, the urgency of more ambitious action is clearer than ever before. China is the world's biggest emitter of greenhouse gases and one of the countries affected most by climate change. The evidence about the impacts of climate change on the environment and human health may encourage China to take more decisive action to mitigate greenhouse gas emissions and adapt to climate impacts. This article aimed to review the evidence of environmental damages and health risks posed by climate change and to provide a new science-based perspective for the delivery of sustainable development goals. Over recent decades, China has experienced a strong warming pattern with a growing frequency of extreme weather events, and the impacts of climate change on China's environment and human health have been consistently observed, with increasing O ₃ air pollution, decreases in water resources and availability, land degradation, and increased risks for both communicable and non-communicable diseases. Therefore, China's climate policy should target the key factors driving climate change and scale up strategic measures to curb carbon emissions and adapt to inevitable increasing climate impacts. It provides new insights for not only China but also other countries, particularly developing and emerging economies, to ensure climate and environmental sustainability whilst pursuing economic growth.
Climate Change ; China ; Humans ; Greenhouse Gases ; Air Pollution ; Sustainable Development ; Environment

OBJECTIVE: To identify the key features of facial and tongue images associated with anemia in female populations, establish anemia risk-screening models, and evaluate their performance. METHODS: A total of 533 female participants (anemic and healthy) were recruited from Shuguang Hospital. Facial and tongue images were collected using the TFDA-1 tongue and face diagnosis instrument. Color and texture features from various parts of facial and tongue images were extracted using Face Diagnosis Analysis System (FDAS) and Tongue Diagnosis Analysis System version 2.0 (TDAS v2.0). Least Absolute Shrinkage and Selection Operator (LASSO) regression was used for feature selection. Ten machine learning models and one deep learning model (ResNet50V2 + Conv1D) were developed and evaluated. RESULTS: Anemic women showed lower a-values, higher L- and b-values across all age groups. Texture features analysis showed that women aged 30-39 with anemia had higher angular second moment (ASM)and lower entropy (ENT) values in facial images, while those aged 40-49 had lower contrast (CON), ENT, and MEAN values in tongue images but higher ASM. Anemic women exhibited age-related trends similar to healthy women, with decreasing L-values and increasing a-, b-, and ASM-values. LASSO identified 19 key features from 62. Among classifiers, the Artificial Neural Network (ANN) model achieved the best performance [area under the curve (AUC): 0.849, accuracy: 0.781]. The ResNet50V2 model achieved comparable results [AUC: 0.846, accuracy: 0.818]. CONCLUSION Differences in facial and tongue images suggest that color and texture features can serve as potential TCM phenotype and auxiliary diagnostic indicators for female anemia.
Humans ; Female ; Tongue/diagnostic imaging* ; Adult ; Anemia/diagnosis* ; Middle Aged ; Face/diagnostic imaging* ; Young Adult ; Machine Learning

OBJECTIVE: The role of cold spells of different intensities in the economic burden of death is crucial for health adaptation to climate change, especially in a multi-site setting. The objective of the study was to explore the economic burden of mortality attributable to cold spells. METHODS: We performed a two-stage time-series analysis using the Value of Statistical Life (VSL) approach to evaluate the economic impact of mortality related to cold spells of varying lengths and intensities. This analysis employed a case-crossover design, with a distributed lag nonlinear model (DLNM) used for analysis. Analysis was stratified according to age, sex, and region of origin. The results of the assessment show that cold spells have an enormous impact on the economic losses of mortality due to climate change and aging. RESULTS: Totally, 8.3% (95% CI: 0.0%, 16.0%) to 13.8% (95% CI: 1.0%, 24.8%) of VSL were ascribed to cold spells, accounting for economic losses of 4.71 (95% CI: 0.34, 8.47) to 11.45 (95% CI: 0.00, 21.00) billion CNY, in the cold season. The population aged over 65 y and females are particularly vulnerable. Economic impacts in warmer regions, such as the southern and subtropical zones, are more extensive than those in the northern and temperate zones. CONCLUSION Customizing cold spell prevention measures for vulnerable populations or regions is vital to alleviating the socioeconomic burden.
China/epidemiology* ; Humans ; Female ; Male ; Cold Temperature/adverse effects* ; Aged ; Middle Aged ; Adult ; Mortality ; Infant ; Child ; Adolescent ; Child, Preschool ; Young Adult ; Climate Change ; Aged, 80 and over ; Cost of Illness ; Infant, Newborn

Objective:To investigate the the differential expression of EIF5A2 in intrahepatic cholangiocarcinoma cell lines RBE,HCCC9810,and HUCCT1,and its effects on HCCC9810 cell migration and invasion,epithelial mesenchymal transition,and PI3K/AKT signaling pathway.Methods:The differential expression of EIF5A2 in RBE,HCCC9810,and HUCCT1 cell lines was detected using WB method.The HCCC9810 cell line,with the highest expression of EIF5A2,was selected for this experiment.The expression of EIF5A2 in HCCC9810 cell line was silenced by transient transfection of small interfering RNA.The best silencing effect of small interfering RNA was screened by WB.Scratch assay and Tran-swell migration invasion assay were used to detect the effect of silencing EIF5A2 on the migration and invasion ability of HCCC9810 cells.WB was used to detect the effect of silencing EIF5A2 on PI3K/AKT signaling pathway and epithelial mesenchymal transition in HCCC9810 cells.Results:The WB results showed that EIF5A2 had the highest expression in the HCCC9810 cell line,and siRNA1 had the best silencing effect on EIF5A2 in the HCCC9810 cell line.Scratch assay and Transwell migration invasion assay results showed that silencing EIF5A2 in the HCCC9810 cell line resulted in a decrease in cell invasion and metastasis ability(P＜0.05).At the same time,the expression of p-PI3K and p-AKT in the PI3K/AKT signaling pathway was significantly decreased(P＜0.05),while the epithelial cell marker E-cadherin expression increased(P＜0.05)and the stromal cell marker N-cadherin expression decreased(P＜0.05).Conclusion:EIF5A2 may promote epi-thelial mesenchymal transition and enhance the migration and invasion ability of intrahepatic cholangiocarcinoma cells through the PI3K/AKT signaling pathway.

Objective:To investigate the clinical characteristics of patients with high-myopia macular hole retinal detachment (MHRD) combined with choroidal detachment and to preliminarily analyze factors associated with postoperative hole closure.Methods:A retrospective clinical case series study. A total of 68 patients with high myopia (68 eyes) with MHRD diagnosed by Department of Ophthalmology, Peking University People’s Hospital from January 2019 to April 2024 were included in this study. Among them, there were 14 males (14 eyes) and 54 females (54 eyes). The mean age was (61.10±9.66) years. All eyes were treated with pars plana vitrectomy (PPV) combined with silicone oil or gas filling. Best corrected visual acuity (BCVA), intraocular pressure, and B-mode ultrasonography were performed. The BCVA test was performed using the Snellen visual acuity chart, which was statistically converted to logarithm of the minimum angle of resolution (logMAR) visual acuity. The range of choroidal detachment was defined according to the number of involved quadrants observed in B-mode ultrasound or surgery, which was divided into 1 to 4 quadrants. Axial length (AL) was measured under retinal reattachment. In 68 eyes, there were 17 eyes with choroidal detachment and 51 eyes without choroidal detachment, respectively. There were 17 eyes with choroidal detachment, and the detachment range involved 1, 2, 2 and 12 eyes in 1, 2, 3 and 4 quadrants, respectively. During operation, 13% C 3F 8 was filled in 2 eyes, all of which were not complicated with choroidal detachment. 66 eyes were filled with silicone oil. According to whether the patients were complicated with choroidal detachment, the patients were divided into the group without choroidal detachment and the group with choroidal detachment. Independent sample t test, Welch two-sample t test or Mann-Whitney U test were used for comparison between groups. Generalized linear regression and logistic regression were used to analyze the relationship between the aperture size of postoperative unclosed holes and the closed hole after surgery and clinical factors. Results:At 3 months after surgery, the logMAR BCVA of the affected eye was 1.29±0.43, with a preoperative to postoperative difference ranging from -1.60 to 0.70 (-0.51±0.51) logMAR units. The AL ranged from 26.6 to 34.3 (29.60±2.12) mm. Among 68 eyes, macular hole of 37 (54.4%, 37/68) eyes were open and 31 (45.6%, 31/68) eyes were closed, respectively. The hole diameter of the open eye was (753±424) μm. There was no significant difference in age, course of disease and AL between the two groups ( W=412.0, 477.5, 427.0; P>0.05). Before operation, BCVA in patients with choroidal detachment was worse ( W=257.5) and intraocular pressure was lower ( t=4.051) in patients with choroidal detachment compared with those without choroidal detachment, with statistical significance ( P<0.05). At 3 months after surgery, BCVA in patients with choroidal detachment was significantly worse than that in patients without choroidal detachment, with statistical significance ( W=284.0, P<0.05). There were no significant differences in logMAR BCVA difference ( t=0.616) and macular hole closure rate ( χ 2=0.000) before and after surgery ( P>0.05). The reoperation rate of retinal detachment due to persistent or recurrent retinal detachment was significantly higher in the group with choroid detachment than in the group without choroid detachment, and the difference was statistically significant (odds ratio=6.424, P<0.05). Logistic regression analysis showed that young age was significantly correlated with macular hole closure failure after surgery ( β=0.077, P=0.015). There was no correlation between AL, duration of disease, BCVA before surgery, intraocular pressure, wether combined with choroid detachment range and postoperative hole closure ( β=-0.072, 0.000, 0.672, -0.085, -0.391; P>0.05). Conclusions:Concomitant choroidal detachment adversely affected on both pre-operative and post-operative visual acuity in high myopia MHRD. It is closely associated with the risk of recurrent retinal detachment and the needs of multiple operations, but has no significant effect on hole closure rate. Lower age of onset may be a risk factor for macular hole closure.

Objective:To observe and analyze the correlation between ectopic foveal inner layer (EIFL) and the EIFL-based idiopathic epiretinal membrane (ERM) staging system and the anatomic and functional prognosis of ERM eyes post pars plana vitrectomy (PPV).Methods:A retrospective study. From January 1, 2020 to October 30, 2023, 345 eyes of 330 patients diagnosed with idiopathic ERM in Department of Ophthalmology of Peking University People's Hospital and treated with standard transciliary flat three-channel 25G PPV combined with ERM and internal limiting membrane exfoliation were included in the study. Among them, 96 were males (111 eyes) and 234 were females (234 eyes). The mean age was (66.8±7.7) years. All study eyes received standard three-port 25G PPV combined with ERM and internal limiting membrane peeling. All study eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. BCVA was performed using a standard logarithmic visual acuity chart and converted to logarithm of the minimum angle of resolution visual acuity for statistical analysis. EIFL thickness and central foveal thickness (CFT) on OCT were measured. ERM eyes were grouped into stage Ⅰ, Ⅱ, Ⅲ and Ⅳ according to ERM staging scheme based on EIFL; disorganization of the retinal inner layers (DRIL) of study eyes were assessed and grouped into no, mild and severe groups. The correlation between ERM staging as well as EIFL thickness and the anatomical and functional prognosis 6 months post-PPV were analyzed.Results:Among 345 study eyes, 12, 87, 174 and 72 eyes were stage Ⅰ-Ⅳ ERM respectively, 63 with no DRIL, 216 with mild DRIL and 66 with severe DRIL. Among the 153 eyes with macular edema, the edema subsided in 66 eyes (43.1%, 66/153) 6 months after the operation. Eighty-seven eyes (56.9%, 87/153) did not regress. The edema subsided 6 months after the operation was not significantly correlated with the ERM stage before the operation ( χ2=3.331, R=?0.145, P=0.304) or the degree of DRIL ( χ2=0.655, R=?0.108, P=0.445). The results of the correlation analysis showed that logMAR BCVA 6 months after the surgery was positively correlated with the degree of DRIL before the surgery ( Tau-b=0.236), ERM stage ( Tau-b=0.194), CFT ( r=0.383), and EIFL thickness ( r=0.317) ( P<0.05). There was no significant correlation with the thickness of the outer nuclear layer before the operation ( r=0.004, P>0.05). Preoperative ERM stage ( Tau-b=0.303, P<0.001) and DRIL severity ( Tau-b= 0.238, P=0.001) were positively correlated with CFT at 6 months after surgery. Conclusion:The ERM stage and EIFL thickness before the operation are positively correlated with logMAR BCVA and CFT 6 months after the operation.