OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective To understand the level of occupational health literacy (OHL) and its influencing factors among occupational population in five key industries of tertiary industry in Putuo District of Shanghai City. Methods A total of 1 159 front-line workers, from five key industries of tertiary industry in Putuo District of Shanghai City in 2023, were selected as the research subjects using the stratified cluster random sampling method. Their OHL levels were surveyed using the Occupational Health Literacy Questionnaire of National Key Populations. Results A total of 1 159 front-line workers in key industries were surveyed, and 476 had OHL, with an overall OHL level of 41.1%. The OHL levels across four dimensions including basic knowledge of occupational health protection, healthy lifestyle and behavior, legal knowledge of occupational health, and basic skills of occupational health protection from high to low were 72.9%,44.5%,42.2%, and 31.3%, respectively. The results of multivariable logistic regression analysis showed that gender, educational level, and industry category were independent influencing factors for OHL level of the research subjects (all P<0.05). Female workers had higher OHL levels than males (P<0.05). Higher education level was associated with higher OHL level in workers (all P<0.05). Workers in industries of medical health had higher OHL level than those in couriers/delivery transportation, education and environmental health(all P<0.01). Conclusion The OHL level of occupational population in the five key industries of tertiary industry in Putuo District of Shanghai City needs to be further improved. Efforts should focus on enhancing health education on legal knowledge and basic skills of occupational health protection, with special attention to workers OHL in the transportation and courier/delivery industries and those with lower education levels.

Diabetic peripheral neuropathy (DPN) is one of the common chronic complications of diabetes, presenting with neuropathic pain, sensory abnormalities, and sensory loss, and may lead to foot infections, ulcers, or amputation in severe cases. Its pathogenesis remains unclear, with challenge in early diagnosis and limited treatment efficacy. Emerging evidences suggest that DPN involves in not only the peripheral nervous system but also the central nervous system (CNS). With advances in imaging technologies, multimodal MRI has become a key tool to investigate CNS involvement in DPN. This review summarizes the structural, functional, metabolic, and perfusion-related CNS changes in DPN patients based on structural MRI, functional MRI, MR spectroscopy, and perfusion-weighted imaging, aiming to help early detection, clinical subtyping, and personalized treatment of DPN.

Peripheral neuropathic pain (PNP) patients exhibit complex and diverse symptoms, often accompanied by abnormal pain and hyperalgesia, which seriously affect their quality of life. Currently, pharmacological treatments for PNP have limited effectiveness and are prone to side effects, making them inadequate for long-term patient needs. Peripheral nerve stimulation (PNS) can relieve pain by precisely stimulating specific peripheral nerves, offering advantages such as minimal invasiveness, broad applicability, and personalized treatment. This article reviews the pathophysiology of PNP and application of PNS in PNP treatment, aiming to provide references for PNP treatment.

Objective:To explore the impact of air pollution on hospital visits for mental and behavioral disorders among residents in an industrial area in Henan Province from 2016 to 2021.Methods:Daily outpatient visits data for mental and behavioral disorders were collected from Angang General Hospital in Angang Industrial Area at Anyang City between January 2016 and December 2021. And air pollutants and meteorological data during the same period were also collected. A generalized additive model was used for time-series analysis to examine the relationship between daily average concentrations of nitrogen dioxide (NO 2), sulfur dioxide (SO 2), fine particulate matter (PM 2.5), inhalable particulate matter (PM 10), carbon monoxide (CO), and ozone (O 3) with a lag of 0 to 7 days on the number of visits for mental and behavioral disorders among residents. The single-day lag effect (lag0-lag7 d) and cumulative lag effect (lag01-lag07 d) were analyzed. The smooth cubic spline function was used to fit the exposure-response relationship, and subgroup analysis was performed according to different genders, seasons and ages. Results:A total of 26 268 hospital visits for mental and behavioral disorders were collected from the industrial area between 2016 and 2021. The daily average concentrations of SO 2, NO 2, PM 2.5, PM 10, and CO were (27.50±27.33), (43.11±18.33), (73.87±60.30), (134.01±83.81) μg/m 3, and (1.72±1.03) mg/m 3, respectively. The daily maximum 8-hour average concentration of O 3 was (82.18±53.70) μg/m 3. After controlling for long-term trends, temperature, relative humidity, day of the week effects, and holiday effects, the generalized additive model analysis showed that NO 2 had a statistically significant impact on the hospital visits for mental and behavioral disorders at lag0 d, lag2 d and lag01-lag05 d and CO had a statistically significant impact at lag0-lag3 d and lag01-lag06 d (all P<0.05). NO 2 at lag02-lag04 d and CO at lag0-lag2 d and lag01-lag04 d had statistically significant effects on the visits for neurasthenia (both P<0.05). The impacts of NO 2 at lag03-lag04 d, PM 2.5 at lag3 d and lag03-lag04 d, PM 10 at lag3 d and lag03 d, and CO at lag3 d and lag01-lag05 d on visits for generalized anxiety disorder were also statistically significant (all P<0.05). After false discovery rate (FDR) correction, it was shown that for every 10 μg/m 3 increase in NO 2 and every 0.1 mg/m 3 increase in CO, the percentage increase in visits for mental and behavioral disorders and its 95% confidence interval (95% CI) were 3.38% (0.95%-5.87%) and 0.78% (0.38%-1.17%), respectively. For every 0.1 mg/m 3 increase in CO, the visits for neurasthenia increased by 0.78% (0.27%-1.29%). For every 10 μg/m 3 increase in PM 2.5 and every 0.1 mg/m 3 increase in CO, the visits for generalized anxiety disorder increased by 1.07% (0.46%-1.68%) and 1.17% (0.37%-1.97%), respectively (adjusted P<0.05). There was a linear exposure-response relationship between NO 2 and CO and the hospital visits for mental and behavioral disorders, CO and the hospital visits for neurasthenia, and CO and PM 2.5 and the hospital visits for generalized anxiety disorder ( P<0.05 for the overall association test and P>0.05 for the non-linearity test). Stratified analysis showed that air pollutants had an impact on male patients with neurasthenia, female patients with generalized anxiety disorder, individuals aged <45 years with mental and behavioral disorders, and individuals aged ≥65 years with generalized anxiety disorder. The impact of air pollutants was greater during the cold season or winter. Conclusion:Exposure to air pollution can increase hospital visits for mental and behavioral disorders among residents in industrial areas, with a higher risk among those aged<45 years old and during the cold season.

The term"heat stroke"originates from the integration of modern traditional Chinese and Western medicine.In clinical practice,the complementary advantages of the two medical systems can significantly enhance the clinical diagnosis and treatment level of heat stroke.Through comprehensively analyzes the traditional Chinese medicine(TCM)nomenclature for heat stroke,proposing that heat stroke is a type of sunstroke characterized by intense and pure yang nature,specifically referring to symptoms caused directly or indirectly by hot weather.It can be referenced under the categories of Zhongye,Shuwen,Yinshu/Yangshu,Shujue,and Shufeng for treatment.The article reviews the TCM diagnostic and therapeutic thinking for heat stroke,summarizing its etiology and pathogenesis,including summerheat directly entering the Yangming,heat entering the heart and nutrient-blood aspects,evil combined with water(post-emergency),dual injury of qi and fluid(post-mild recovery),and phlegm-stasis obstructing collaterals(post-severe recovery).Based on years of clinical experience and combining the different clinical manifestations of heat stroke with TCM's four diagnostic methods,the article proposes a treatment plan that integrates Chinese and Western medicine,combining disease differentiation with syndrome differentiation.The main syndromes summarized include high fever with spasms(Yangming heat excess syndrome),diarrhea(Yangming fu syndrome-intestinal sweating),high fever with coma(heat entering the heart-nutrient syndrome),high fever with convulsions(extreme heat generating wind syndrome),heat stroke-induced coagulopathy(heat entering the blood aspect syndrome),edema after fluid resuscitation(Taiyang water retention syndrome),recovery phase(dual injury of qi and fluid syndrome),and sequelae(phlegm-stasis obstructing collaterals syndrome).For treatment,Baihu Jia Renshen decotion combined with Zengye Chengqi decotion is used for nourishing yin and increasing fluids,relaxing tendons,and stopping spasms for Yangming heat excess syndrome;Baihu decotion combined with Zengye decotion for clearing summerheat and nourishing yin for Yangming fu syndrome-intestinal sweating;Qingying decotion for clearing the nutrient aspect and cooling blood,penetrating heat,and nourishing yin for heat entering the heart-nutrient syndrome;Lingjiao Gouteng decotion for clearing heat and cooling the liver,extinguishing wind,and calming spasms for extreme heat generating wind syndrome;Wuling powder for draining and eliminating water retention for Taiyang water retention syndrome;Wang's Qing Shu Yiqi decotion for clearing summerheat and reducing fever,benefiting qi,and generating fluids for dual injury of qi and fluid syndrome;and Sanjia powder for clearing residual heat,resolving phlegm,and removing stasis from collaterals for phlegm-stasis obstructing collaterals syndrome.Starting from TCM theory and linking it with practice,the article combines Western disease differentiation with TCM syndrome differentiation,aiming to provide new ideas for the clinical treatment of heat stroke.

Objective To quantitatively evaluate the structure and content of the long-term care insurance(LTCI)policy in China's deeply aging areas.Methods Using the Policy Modeling Consistency(PMC)index model indicator design method,a LTCI policy evalua-tion index system was constructed,consisting of nine primary indicators and 34 secondary indicators.A total of 123 provincial-level LTCI policies issued in deeply aging regions of China between June 1,2014,and October 1,2024 were analyzed.High-frequency word extraction was performed using ROSTCM 6.0,and a social network diagram of LTCI policies was created.The policy structure and content were quantitatively evaluated and ana-lyzed based on the established policy evaluation index system.Results The main content of LTCI policies in deeply aging areas of China covered services,institutions and assessment.The highest policy score was 7.28,and the lowest was 2.20,with an average score of 5.00.There were 25 perfect policies,63 excellent policies,28 good policies and seven qualified policies.In the dimension of policy content,the indexes of five primary indicators of policy evaluation,policy target groups,policy nature,policy perspective and policy tools were 0.60 or more;while the indexes of four primary indicators of policy content,incentives and constraints,policy timeliness,and policy level were 0.50 or less.Conclusion LTCI policies issued in China's deeply aging areas provide comprehensive coverage in aspects such as poli-cy evaluation,policy target groups and policy nature,and need to be improved in policy tool selection and the construction of incentive and constraint mechanisms.

In the century-long evolution of insulin pharmaceuticals, each transformative advancement in this drug class has been closely tied to the ability to obtain new insulin isoforms for research. Despite this, the recently discovered naturally occurring isoforms of glycosylated human insulin have remained largely unattainable for proper characterization. Herein, we demonstrate for the first time that total chemical synthesis can be used to generate all isoforms. This achievement required maintaining the correct positions of the interchain disulfide bonds while effectively removing protecting groups on complex glycans. Notably, the availability of seven glycoforms reveals the important effects of natural sialylated glycans in suppressing insulin self-association and enhancing its solubility, surpassing the performance of currently employed rapid-acting insulin drugs. This work not only offers a readily adaptable platform for exploring natural O-glycosylation in other therapeutic proteins and peptides but also lays the groundwork for further research into harnessing natural glycosylation for therapeutic applications.