BACKGROUND:Studies have shown that mitochondrial oxidative stress has an important role in the development of knee osteoarthritis,and Hemin can regulate the expression of mitochondria-related proteins. OBJECTIVE:To study the regulatory effect of Hemin on oxidative stress in mouse chondrocytes and its interventional effect and mechanism in knee osteoarthritis. METHODS:(1)In vitro cell experiment:Primary chondrocytes from C57BL/6 mice were extracted and induced with 10 ng/mL interleukin-1β to construct an in vitro chondrocyte model of osteoarthritis.The optimal concentration of Hemin(0,1,10,20,40,80,and 160 μmol/L)for the intervention in mouse chondrocytes was determined by cell counting kit-8 method.Chondrocytes were randomly divided into control group,model group(interleukin-1β)and Hemin group(interleukin-1β+Hemin).Reactive oxygen species,mitochondrial membrane potential and apoptosis of chondrocytes in each group were detected.(2)In vivo experiment:Adult C57BL/6 mice were randomly divided into normal group,model group(osteoarthritis)and Hemin group(osteoarthritis+Hemin),with eight mice in each group.After 4 weeks of Hemin treatment,the behavioral test and histopathological observation of the knee joint were performed in each group.Changes in extracellular matrix-related protein expression and apoptosis in chondrocytes and the expression level of Nrf2/HO-1 protein in cartilage tissue were detected. RESULTS AND CONCLUSION:In vitro experiment:the optimal concentration of Hemin on primary chondrocytes was 40 μmol/L.Compared with the model group,the level of reactive oxygen species was significantly reduced,the mitochondrial membrane potential was significantly improved,and the apoptosis of chondrocytes was reduced in the hemin-treated interleukin-1β-induced chondrocytes.In vivo experiment:After 4 weeks of treatment,compared with the model group,the lower limb function of mice in the Hemin group was significantly improved,the histopathological score was significantly improved,and the apoptosis of knee chondrocytes was significantly reduced.All these findings indicate that Hemin can alleviate oxidative stress,restore mitochondrial function and reduce apoptosis in mouse chondrocytes induced by interleukin-1β.Hemin can improve extracellular matrix degradation,promote chondrocyte anabolism,reduce catabolism and reduce chondrocyte apoptosis in knee osteoarthritis.It may act by activating the chondrocyte Nrf2/HO-1 signaling pathway in the inflammatory environment.

Objective: To analyze the temporal variation patterns of sickness absenteeism among primary and secondary school students in Shanghai, so as to explore models suitable for predicting peaks and intensity of absenteeism rates. Methods: The seasonal and trend decomposition using loess (STL) method was used to analyze the seasonal and long term trend changes in sickness absenteeism among primary and secondary school students from September 1 in 2010 to June 30 in 2018, in Shanghai. A hierarchical clustering method based on Dynamic Time Warping (DTW) was employed to classify absenteeism symptoms with similar temporal patterns. Based on historical data, the study constructed and evaluated different time series algorithms and machine learning models to optimize the accuracy of predicting the trend of sickness absenteeism. Results: During the research period, the average new absenteeism rate due to illness was 16.86 per 10 000 person day for every academic year, and the trend of sickness absenteeism exhibited both seasonality and a long term upward trend, reaching its highest point in the 2017 academic year (22.47 per 10 000 person day). The symptoms of absenteeism were divided into three categories: high incidence in winter and spring (respiratory symptoms, fever and general discomfort, etc.), high incidence in summer (eye symptoms, nosebleeds, etc.) and those without obvious seasonality (skin symptoms, accidental injuries, etc.).The constructed time series models effectively predicted the trend of absenteeism due to illness, although the accuracy of predicting peak intensity was relatively low. Among them, the multi layer perceptron (MLP) model performed the best, with an root mean squared error (RMSE) of 8.96 and an mean absolute error (MAE) of 4.37, reducing 36.51% and 39.02% compared to the baseline model. Conclusion Time series models and machine learning algorithms could effectively predict the trend of sickness absenteeism, and corresponding prevention and control measures can be taken for absenteeism caused by different symptoms during peak periods.

ObjectiveTo analyze the development trajectory， research hotspots， and trends in medical humanities research in China since the new era. MethodsA search was conducted on the CNKI （China National Knowledge Infrastructure） advanced search page using the themes“medical humanities”or “humanistic medicine，”retrieving a total of 5，758 articles. After applying specific screening criteria， 5，095 articles were included in the analysis. Citespace6.1.R6 was used to visualize and analyze the authors， institutions， and keywords of the 5，095 articles. ResultsSince the new era， the volume of publications on medical humanities in China has shown an overall upward trend， with limited collaboration between core institutions and core authors. The research content of medical humanities has evolved from broad to specific， from abstract to concrete， and from theoretical to practical. ConclusionThe development of medical humanities research in China has generally gone through three stages： defining related concepts， integrating medical humanistic spirit into clinical practice， and applying empirical methods. Narrative medicine， ideological and political education in curricula， and medical humanities education are potential future research directions.

Objective To explore the research hotspots and development trends in the field of cancer treatment in the past decade. Methods The CNKI and Web of Science Core Collection databases were searched for Chinese and English articles related to cancer treatment published over the last 10 years. Bibliometric research methods were employed, including keyword cluster analysis of published literature. Results A total of 45 455 Chinese articles and 866 958 English articles were retrieved. Combining the visualization analysis results and the current research dilemma of tumor treatment revealed that the current research hotspots of tumor treatment domestically and internationally can primarily focus on four key areas. In the realm of targeted therapy, efforts are directed towards the discovery of new drug targets, overcoming resistance to targeted therapy, and the development of monoclonal antibodies and antibody–drug conjugates. In the field of immunotherapy, the emphasis lies in enhancing the response rate to immune checkpoint inhibitors, determining the mechanisms behind resistance to immunotherapy, and improving the safety of treatment. The research in traditional Chinese medicine (TCM) covers evidence-based evaluation studies on TCM treatment, the identification of populations that can gain the most benefit from TCM, and strategies for improving the quality of life. In the area of novel drug development, cutting-edge technologies, such as organoid-based screening for anticancer drugs, synthetic biology, and artificial intelligence, are under investigation. Conclusion New targeted drugs, immune efficacy improvement, multidisciplinary integration, nano-delivery, and TCM innovation are the key research directions in the field of tumor therapy in the future.

Based on the viewpoint of "sweat pore-qi and liquid-kidney collaterals"， it is believed that children's nephrotic syndrome is caused by the core mechanism of sweat pore constraint and closure， qi and liquid imbalance， and kidney collaterals impairment， and it is proposed that the treatment principle is to nourish the sweat pore， regulate qi and fluid， and supplement the kidney and unblock the collaterals. In clinic， guided by sequential therapy and according to the different disease mechanism characteristics of the four stages， including early stage of the disease， hormone induction stage， hormone reduction stage， hormone maintenance stage， the staged dynamic identification and treatment was applied. For early stage of the disease with edema due to yang deficiency， modified Zhenwu Decoction （真武汤） was applied to warm yang and drain water； for hormone induction stage with yin deficiency resulting in effulgent fire， modified Zhibai Dihuang Pill （知柏地黄丸） plus Erzhi Pill （二至丸） was used to enrich yin and reduce fire； for hormone reduction stage with qi and yin deficiency， modified Shenqi Dihuang Decoction （参芪地黄汤） was used to boost qi and nourish yin； for hormone maintenance stage， modified Shenqi Pill （肾气丸） was used to supplement yin and yang. Meanwhile， the treatment also attaches importance to the combination of vine-based or worm medicinals to dredge collaterals， so as to providing ideas for clinical treatment.

Membrane proteins are integral components of cellular membranes, accounting for approximately 30% of the mammalian proteome and serving as targets for 60% of FDA-approved drugs. They are critical to both physiological functions and disease mechanisms. Their functional protein-protein interactions form the basis for many physiological processes, such as signal transduction, material transport, and cell communication. Membrane protein interactions are characterized by membrane environment dependence, spatial asymmetry, weak interaction strength, high dynamics, and a variety of interaction sites. Therefore, in situ analysis is essential for revealing the structural basis and kinetics of these proteins. This paper introduces currently available in situ analytical techniques for studying membrane protein interactions and evaluates the characteristics of each. These techniques are divided into two categories: label-based techniques (e.g., co-immunoprecipitation, proximity ligation assay, bimolecular fluorescence complementation, resonance energy transfer, and proximity labeling) and label-free techniques (e.g., cryo-electron tomography, in situ cross-linking mass spectrometry, Raman spectroscopy, electron paramagnetic resonance, nuclear magnetic resonance, and structure prediction tools). Each technique is critically assessed in terms of its historical development, strengths, and limitations. Based on the authors’ relevant research, the paper further discusses the key issues and trends in the application of these techniques, providing valuable references for the field of membrane protein research. Label-based techniques rely on molecular tags or antibodies to detect proximity or interactions, offering high specificity and adaptability for dynamic studies. For instance, proximity ligation assay combines the specificity of antibodies with the sensitivity of PCR amplification, while proximity labeling enables spatial mapping of interactomes. Conversely, label-free techniques, such as cryo-electron tomography, provide near-native structural insights, and Raman spectroscopy directly probes molecular interactions without perturbing the membrane environment. Despite advancements, these methods face several universal challenges: (1) indirect detection, relying on proximity or tagged proxies rather than direct interaction measurement; (2) limited capacity for continuous dynamic monitoring in live cells; and (3) potential artificial influences introduced by labeling or sample preparation, which may alter native conformations. Emerging trends emphasize the multimodal integration of complementary techniques to overcome individual limitations. For example, combining in situ cross-linking mass spectrometry with proximity labeling enhances both spatial resolution and interaction coverage, enabling high-throughput subcellular interactome mapping. Similarly, coupling fluorescence resonance energy transfer with nuclear magnetic resonance and artificial intelligence (AI) simulations integrates dynamic structural data, atomic-level details, and predictive modeling for holistic insights. Advances in AI, exemplified by AlphaFold’s ability to predict interaction interfaces, further augment experimental data, accelerating structure-function analyses. Future developments in cryo-electron microscopy, super-resolution imaging, and machine learning are poised to refine spatiotemporal resolution and scalability. In conclusion, in situ analysis of membrane protein interactions remains indispensable for deciphering their roles in health and disease. While current technologies have significantly advanced our understanding, persistent gaps highlight the need for innovative, integrative approaches. By synergizing experimental and computational tools, researchers can achieve multiscale, real-time, and perturbation-free analyses, ultimately unraveling the dynamic complexity of membrane protein networks and driving therapeutic discovery.

ObjectiveTo establish the multi-technique characteristic profiles of Alumen by X-ray diffraction（XRD）， Fourier-transform infrared spectroscopy（FTIR） and thermogravimetric-differential thermal analysis（TG-DTA）， and to explore the spectral characteristics for rapid identification of Alumen and its potential adulterant， Ammonium alum. MethodsA total of 27 batches of Alumen samples from 8 production regions were collected for preliminary identification based on visual characteristics. The PDF standard cards of XRD were used to differentiate Alumen from A. alum， and the XRD characteristic profiles of Alumen were established， and then the common peaks were screened. Based on hierarchical clustering analysis（HCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， the characteristic information that could be used for identification of Alumen was selected with variable importance in the projection（VIP） value>1. FTIR characteristic profiles of Alumen were established， and key wavenumbers for identification were screened by HCA and OPLS-DA with VIP value>1. Meanwhile， the thermogravimetric differences between Alumen and A. alum were analyzed by TG-DTA， and the thermogravimetric traits that could be used for identification were screened. ResultsAlumen and A. alum could not be effectively distinguished by traits alone. However， by comparing the PDF standard cards of XRD， 15 batches of Alumen and 12 batches of A. alum could be distinguished. In the XRD profiles， 10 characteristic peaks were confirmed， corresponding to diffraction angles of 14.560°， 24.316°， 12.620°， 32.122°， 17.898°， 34.642°， 27.496°， 46.048°， 40.697° and 21.973°. In the FTIR profiles， 4 wavenumber ranges（399.193-403.050， 1 186.010-1 471.420， 1 801.190-2 620.790， 3 612.020-3 997.710 cm^-1） and 12 characteristic wavenumbers（1 428.994， 1 430.922， 1 432.851， 1 434.779， 1 436.708， 1 438.636， 1 440.565， 1 442.493， 1 444.422， 1 446.350， 1 448.279， 1 450.207 cm^-1） were identified. In the TG-DTA profiles， there were characteristic decomposition peaks of ammonium ion and mass reduction features near 555.34 ℃ for A. alum. These characteristics could serve as important criteria for distinguishing the authenticity of Alumen. ConclusionXRD， FTIR and TG-DTA can be used to rapidly detect Alumen and A. alum， and combined with the discriminant features selected through chemometrics， the rapid and accurate identification of Alumen and A. alum can be achieved. The research findings provide new approaches for the rapid identification of Alumen.

Systemic lupus erythematosus （SLE）， a refractory autoimmune disease， is among the dominant diseases where traditional Chinese medicine （TCM） shows advantages in the field of rheumatology and immunology. The China-Japan Friendship Hospital hosted the "46^th Youth Salon on Dominant Diseases （Systemic Lupus Erythematosus）" organized by the China Association of Chinese Medicine， which led to a consensus on "the advantages， challenges， interdisciplinary approaches， and translational achievements of integrated TCM and Western medical approaches in the diagnosis and treatment of SLE." The diagnosis and treatment of SLE currently face several challenges， such as frequent misdiagnosis and missed diagnosis in the early stages， difficulty in achieving treatment targets， multiple side effects from pharmacotherapy， and the lack of management strategies for special populations， all of which hinder the fulfillment of the clinical needs of patients. Integrated TCM and Western medical approaches can improve clinical symptoms such as skin erythema， aversion to cold and cold limbs， fatigue， dry mouth， restlessness， and heat sensation in the palms and soles， thereby improving patients' quality of life. The approaches also help consolidate the efficacy of conventional Western medicine， slow disease progression， reduce relapse rates， address multi-organ involvement， and prevent or treat complications. Additionally， they enhance efficacy and reduce toxicity， prevent the side effects of Western medications， help reduce hormone use， and offer distinct advantages in the individualized intervention of special populations， contributing to the whole-process management of the disease. However， evidence-based medical support for this integrated approach remains limited， and the quality of available evidence is generally low. Common evaluation systems and modern research methodologies should be adopted to clarify the efficacy of TCM in SLE treatment. Efforts should be made to carry out high-quality evidence-based medical research， strengthen the development of fundamental and pharmacological research， and further explain the distinct advantages of TCM in the diagnosis and treatment of SLE. Future efforts should focus on advancing the integration of TCM and modern medicine， incorporating multi-omics technologies， individualized stratification， and other precision medicine concepts， in combination with artificial intelligence. Moreover， interdisciplinary collaboration should be promoted to utilize modern technology in exploring the essence of TCM theories and screening effective formulae， thereby comprehensively improving the diagnosis and treatment of SLE through integrated TCM and Western medical approaches.

ObjectiveTo explore the construction and evaluation methods of a rat model of acute myocardial infarction（AMI） with Qi and Yin deficiency syndrome established by sleep deprivation combined with coronary artery ligation. MethodsThirty-six SD rats were randomly divided into a normal group（n=6）， a myocardial infarction group（model A group， n=10）， an acute sleep deprivation+myocardial infarction group（model B group， n=10）， and a chronic sleep deprivation+myocardial infarction group（model C group， n=10） according to body weight. Rats in the normal group were not treated， rats in the model A group underwent only ligation of the left anterior descending coronary artery， rats in the model B group were sleep deprived for 96 h and then underwent ligation of the left anterior descending coronary artery， and rats in the model C group were sleep deprived for an additional 48 h each week with a 24 h rest period as one cycle for three weeks on the basis of the model B group. After coronary artery ligation in the model C group， the first week was defined as the starting point of the first sleep deprivation cycle， and indexes were tested weekly for rats in each group for 3 weeks. Electrocardiogram was used to determine the ligation of the left anterior descending coronary artery in rats， and small animal echocardiography was used to evaluate the cardiac function. The levels of serum creatine kinase（CK）， creatine kinase isoenzyme（CK-MB）， lactate dehydrogenase（LDH）， cardiac troponin T（cTnT）， interleukin-18（IL-18）， and tumor necrosis factor-α（TNF-α） were detected by biochemical assays， and hematoxylin-eosin（HE） staining was used to evaluate the pathological changes of myocardial tissue in rats. The syndrome indicators of Qi and Yin deficiency were evaluated by general state and body weight， grip strength， facial temperature， paw temperature， rectal temperature， salivary flow rate， open field test， tongue color［red（R）， green（G）， and blue（B）］ values， pulse amplitude changes， and enzyme-linked immunosorbent assay（ELISA） for the detection of expression levels of cyclic adenosine monophosphate（cAMP）， cyclic guanosine monophosphate（cGMP）， rat serum corticotropin-releasing factor（CRF）， adrenocorticotropic hormone（ACTH）， triiodothyronine（T3）， tetraiodothyronine（T4）， and corticosterone（CORT） in serum. ResultsIn terms of disease indicators， compared with the normal group， the ST segment of the electrocardiogram in each model group was significantly elevated， the echocardiographic parameters were decreased， the contents of myocardial enzymes and inflammatory factors were increased（P<0.01）， and the myocardial tissue in the infarcted area was significantly damaged. In terms of syndrome indicators， compared with the normal group， the body weight of rats in the model B and C groups decreased at each time point， the grip strength of each model group decreased， the total distance traveled and the number of entries into the center in the open field test decreased， the immobility time increased， the facial and rectal temperatures of rats in the model B and C groups increased， the salivary flow rate of each model group decreased， the tongue color was bright red or light， the tongue body was dry or smooth like a mirror， lacking of moisture sensation， the R， G and B values of the tongue surface increased， the pulse amplitude changes decreased， and the contents of T3 and T4 increased， while the expressions of cAMP， CRF， ACTH and CORT in the model B and C groups increased（P<0.05， P<0.01）. ConclusionContinuous sleep deprivation for 96 h in a multi-platform method combined with coronary artery ligation can construct a rat model of AMI with Qi and Yin deficiency syndrome， and the syndrome manifestations can be maintained for 3 weeks.

ObjectiveTo explore the feasibility， evaluation methods and metabolic differences of high-fat diet（HFD） combined with myocardial ischemia-reperfusion injury（MIRI） to establish a rat model of myocardial ischemia-reperfusion with phlegm and blood stasis blocking collaterals syndrome（PBSBCS）. MethodsThirty-two SD rats were randomly divided into the sham operation， HFD， MIRI， and MIRI+HFD groups. Rats in the sham operation and MIRI groups were fed a standard diet（regular chow）， while the HFD and MIRI+HFD groups received a HFD for 10 weeks. Rats in the MIRI and MIRI+HFD groups underwent myocardial ischemia-reperfusion surgery， while the sham operation group underwent only thread placement without ligation. Cardiac function was assessed via small-animal echocardiography， including left ventricular ejection fraction（EF）， left ventricular fractional shortening（FS）， cardiac output（CO）， and stroke volume（SV）. Serum levels of creatine kinase（CK）， CK-MB， triglyceride（TG）， total cholesterol（TC）， high-density lipoprotein cholesterol（HDL-C）， low-density lipoprotein cholesterol（LDL-C）， lactate dehydrogenase（LDH）， endothelin-1（ET-1）， endothelial nitric oxide synthase（eNOS）， tumor necrosis factor-α（TNF-α）， interleukin-18（IL-18）， oxidized LDL（ox-LDL）， and cardiac troponin T（cTnT） were measured by biochemical assays and enzyme-linked immunosorbent assay（ELISA）. Myocardial histopathology was evaluated via hematoxylin-eosin（HE） staining， while myocardial infarction and no-reflow area were assessed using 2，3，5-triphenyltetrazolium chloride（TTC）， Evans blue， and thioflavin staining. Changes in syndrome characteristics［body weight， tongue surface red-green-blue ［RGB］ values， and pulse amplitude］ of PBSBCS were recorded. Serum differential metabolites were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS）. ResultsCompared with the sham operation group， the HFD and MIRI+HFD groups showed significant increases in body weight（P<0.01）， RGB values and pulse amplitude decreased in the HFD， MIRI and MIRI+HFD groups， TC， TG， LDL-C and ox-LDL levels increased in the HFD and MIRI+HFD groups， while HDL-C decreased. Blood perfusion peak time and myocardial no-reflow area increased， serum eNOS level decreased， and CK-MB， LDH， and cTnT activities increased in the HFD， MIRI and MIRI+HFD groups（P<0.05， P<0.01）. Whole blood viscosity was increased in the HFD group at medium shear rate， and in the MIRI and MIRI+HFD groups at low， medium and high shear rates（P<0.05， P<0.01）. Platelet aggregation rate increased in the MIRI and MIRI+HFD groups， accompanied by elevated ET-1， TNF-α， and IL-18 levels， reduced cardiac function indices， expanded myocardial no-reflow and infarction areas， and increased serum CK， CK-MB， LDH， and cTnT activities（P<0.05， P<0.01）. Compared with the MIRI group， the HFD and MIRI+HFD groups showed significant increase in body weight， TC， TG， LDL-C and ox-LDL levels， and significant decrease in HDL-C content（P<0.01）. The MIRI+HFD group showed decrease in RGB values and pulse amplitude， and an increase in whole blood viscosity， platelet aggregation， blood perfusion peak time， myocardial no-reflow and infarction areas， elevated ET-1， TNF-α and IL-18 levels， decreased eNOS content， EF and SV， increased serum CK， CK-MB and cTnT activities， and worsened myocardial pathology（P<0.05）. Compared with the HFD group， the MIRI+HFD group showed similar aggravated trends（P<0.05， P<0.01）. Metabolomics results showed that 34 potential biomarkers involving 13 common metabolic pathways were identified in the MIRI+HFD group compared with the sham operation group. ConclusionThe MIRI group resembles blood stasis syndrome in hemodynamics and myocardial injury， and the HFD group mirrors phlegm-turbidity syndrome in lipid profiles and tongue characteristics. While the MIRI+HFD group aligns with PBSBCS in comprehensive indices， effectively simulating clinical features of coronary heart disease（CHD）， which can be used for the evaluation of the pathological mechanism and pharmacodynamics of CHD with PBSBCS.