BACKGROUND:Low temperatures have detrimental effects on the human cardiovascular system,with a higher prevalence of hypertension and related cardiovascular diseases,especially among people living in cold climates.Transient receptor potential M8(TRPM8)is often recognized as a physiological sensor of environmental cold,and glutamate receptor-3(GLR-3)/glutamate receptor ionotropic,kainate 2(GluK2)is also cold-sensitive.However,the specific molecular mechanisms of cold-associated TRPM8 and GLR-3/GluK2 in regulating hypertension remain puzzling.OBJECTIVE:Through a review of the literature in this field,to find out the general pattern of TRPM8 and GLR-3/GluK2 in regulating the body's cold response,as well as the specific mechanism of action in hypertension,thereby providing a theoretical basis for subsequent research on the treatment of hypertension based on cold-stimulation-related targets,and further expanding the new ideas and methods for the treatment of hypertension.METHODS:We searched,reviewed and screened the relevant literature on"cold stimulation,TRPM8,GLR-3/GluK2 and hypertension"to lay the theoretical foundation for the analysis of the whole article.Comparative analysis method,through reading and analyzing the obtained literature,comparing the similarities and differences between the literature,was performed to provide reasonable theoretical support for the argument.Through further comparative analysis of the literature,the relationship between the relevant indicators was clarified,and the ideas were clarified for the analysis of the full text.RESULTS AND CONCLUSION:(1)TRPM8 can be activated by cold and mainly mediates cool temperature perception in mammals.Its activation can trigger neurogenic inflammatory response and indirectly affect the inflammatory process.Abnormal TRPM8 signal can lead to excessive activation of immune cells,which is significantly associated with the occurrence and development of hypertension.(2)The activation threshold of GLR-3/GluK2 is lower than that of TRPM8,which may preferentially respond to noxious cold stimulation rather than ordinary cool temperature.In cold environment,GLR-3/GluK2 activation enhances sympathetic nerve excitability by regulating interneuron signal transduction and causes peripheral vascular constriction.Long-term effects can lead to increased peripheral vascular resistance.To conclude,TRPM8 and GLR-3/GluK2 are involved in the interaction of the nerve-immune-vascular system by sensing different cold stimuli.Abnormal TRPM8 signaling indirectly promotes the progression of hypertension through inflammation and immune dysregulation,while GLR-3/GluK2 directly exacerbates vascular constriction and resistance by enhancing sympathetic nerve activity.The combination of the two factors may constitute the key molecular mechanism of the occurrence and development of hypertension in cold environment,and provide a potential target for the intervention of cold-related cardiovascular diseases.

BACKGROUND:Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.In recent years,exercise has been used as an intervention therapy for microvascular dysfunction in patients with type 2 diabetes.However,few studies have systematically explored the influence of factors,such as"exercise type,exercise intensity and amount of exercise,"on microvascular function in patients.To some extent,this limits the formulation of precise exercise prescriptions to improve microvascular dysfunction in patients with type 2 diabetes and the comparison of study results.OBJECTIVE:To investigate the effects of exercise type,intensity,frequency and amount of exercise on microvascular function in patients with type 2 diabetes mellitus,and to make suggestions on exercise prescription.METHODS:The first author used computer to search the studies on the improvement of microvascular function in type 2 diabetes patients involving exercise in CNKI,WanFang,PubMed and other databases.The search terms were"diabetes mellitus,type 2 diabetes mellitus,microcirculation,microvascular reactivity,microvessels,capillaries,vasodilation,blood perfusion volume,endothelial cells,shear stress,exercise,aerobic exercise,resistance exercise,high-intensity exercise"in Chinese and English.The articles were screened by a quick glance at the article titles and abstracts to exclude those that were not closely related to the topic,and finally 60 articles were included for review.RESULTS AND CONCLUSION:(1)Exercise is an effective way to improve microvascular function in patients with type 2 diabetes.Aerobic exercise lasting 12-24 weeks,3-5 times/week,exercise time＞30 minutes and intensity between 40％and 59％reserve oxygen intake can significantly improve microvascular function in patients with type 2 diabetes.On the basis of aerobic exercise,systemic resistance exercise 2-3 times a week(50％-85％1RM,every other day)or pressure resistance exercise can obtain better intervention effects.(2)In addition,exercise can improve microvascular function in patients with type 2 diabetes in a"dose-effect"manner,and patients can get better results from the intervention by increasing the amount of exercise,while maintaining safety.(3)The mechanism of exercise improving microvascular function in patients with type 2 diabetes is mainly related to promoting the release of nitric oxide and vascular endothelial growth factor from endothelial cells and inhibiting the release of endothelin1.

Objective:To investigate the diagnostic consistency of extrauterine growth restriction (EUGR) assessed by the Fenton 2013 preterm growth charts (Fenton 2013) and the growth charts by International Fetal and Newborn Growth Consortium for the 21st Century (IG-21).Methods:This multicenter retrospective cohort study included 5 591 preterm infants with a gestational age (GA) at birth of less than 32 weeks admitted to 19 member hospitals of the Neonatal Perinatal Collaborative Network of Suxinyun from January 1 st, 2019, to December 31 st, 2024. Clinical data including baseline characteristics, complications, feeding practices and anthropometrics were processed and analyzed. EUGR was assessed using both the Fenton 2013 and the IG-21. A decrease in weight Z-score at discharge compared to admission by more than 1 was defined as longitudinal EUGR, and discharge weight below the P10 for the corresponding corrected GA was defined as cross-sectional EUGR. Diagnostic consistency was assessed using the Kappa coefficient between the 2 standards, and diagnostic performance of the 2 standards was compared using the McNemar test. Risk factors for EUGR under different definitions were analyzed using univariate analysis and multivariate Logistic regression analysis. Results:A total of 5 591 preterm infants were included, with a GA at birth of (29.7±1.6) weeks and a birth weight of (1 360±315) g and at discharge with a corrected GA of (36.3±2.0) weeks and weight of (2 246±370) g. Detection rates of cross-sectional and longitudinal EUGR diagnosed by Fenton 2013 were both higher than those by IG-21 (37.0% (2 214/5 991) vs. 23.7% (1 324/5 591), 61.1% (3 662/5 991) vs. 30.7% (1 714/5 591), χ2=326.77 and 1 358.05, both P<0.001). Using Fenton 2013 as a reference, IG-21 demonstrated superior diagnostic value and consistency in identifying cross-sectional EUGR compared with longitudinal EUGR (sensitivity of 100.0% (3 377/3 377) vs. 99.6% (1 922/1 929), specificity of 59.8% (1 324/2 214) vs. 46.6% (1 707/3 662), positive predictive value of 79.1% (3 377/4 267) vs. 49.6% (1 922/3 877), negative predictive value of 100.0% (1 324/1 324) vs. 99.6% (1 707/1 714), accuracy of 84.1% (4 701/5 591) vs. 64.9% (3 629/5 591), and Kappa 0.64 vs. 0.37, all P<0.001). In multivariate Logistic regression models, risk factors common to EUGR across both standards included smaller GA at birth, lower birth weight, boy, early-onset sepsis, late-onset sepsis and the elder age at full enteral feeding (all P<0.05). Hemodynamically significant patent ductus arteriosus remained an independent risk factor for longitudinal EUGR regardless of whether by the Fenton 2013 or IG-21 standard (adjust odds ratio ( aOR) =1.25 and 1.27, 95% CI 1.09-1.42 and 1.11-1.45). In addition, under the IG-21 standard, severe bronchopulmonary dysplasia was an independent risk factor for cross-sectional EUGR ( aOR=1.54, 95% CI 1.00-2.38), while severe necrotizing enterocolitis was an independent risk factor for longitudinal EUGR ( aOR=2.18, 95% CI 1.01-4.73). Conclusions:IG-21 showed lower detection rates of both cross-sectional and longitudinal EUGR than Fenton 2013, suggesting greater clinical applicability of IG-21 by reducing overdiagnosis while maintaining sensitivity for predicting complications. Across both standards, cross-sectional EUGR facilitates early identification of growth restriction, whereas longitudinal EUGR better tracks dynamic growth patterns and complications of preterm infants.

OBJECTIVE To investigate the application status of prescription pre-review systems in healthcare institutions of Yunnan province， evaluate their system functions and management capabilities， and provide a practical basis for promoting rational drug use. METHODS A questionnaire survey was conducted among public healthcare institutions at or above the secondary level in Yunnan province to investigate the deployment status of the systems. A capability maturity assessment framework was constructed， encompassing 6 dimensions and 39 indicators， including real-time prescription review， prescription correlation review， rule setting， evidence-based information support， prescription authority management， and system operation management. This framework was then used to evaluate the institutions that had implemented the pre-review systems. RESULTS A total of 100 valid questionnaires were collected， with 37 institutions having adopted prescription pre-review systems， mainly tertiary hospitals. The system predominantly adopted a modular architecture and was embedded into the hospital information system through application programming interfaces and middleware， providing certain capabilities for real-time prescription risk identification. Evaluation results indicated that basic functions such as reviewing indications， contraindications， and drug compatibility performed well， while deficiencies remained in functions related to parenteral nutrition prescription， review of drug dosage for specific diseases， individual patient characteristic recognition， and rule setting. Moreover， the construction of review centers and establishment of management systems were also not well-developed. CONCLUSIONS The overall application rate of prescription pre-review systems in Yunnan province remains low. System functions and management mechanisms require further improvement. It is recommended to enhance information infrastructure in lower-level institutions and explore regionally unified review models to promote standardized and intelligent development of prescription review practices.

ObjectiveTo investigate the differences in the regulatory effects of formulas containing Ephedrae Herba and Armeniacae Semen Amarum （Mahuangtang， Sanaotang， and Maxing Shigantang） on thermosensitive transient receptor potential ion channels （thermo TRPs） in the mouse model of asthmatic airway inflammation. MethodsSixty female C57BL/6 mice were allocated into blank， model， dexamethasone （0.75 mg·kg^-1）， Mahuangtang （3.8 g·kg^-1）， Sanaotang （2.8 g·kg^-1）， and Maxing Shigantang （6.6 g·kg^-1） groups （n=10）. The mouse model of asthma was established with ovalbumin （OVA） and treated with normal saline （blank group） or corresponding drugs （10 mL·kg^-1）， once a day， 19-28 days after modeling. The levels of eosinophils （EOS） in peripheral blood and white blood cell （WBC） in bronchoalveolar lavage fluid （BALF）， changes in enhanced pause （Penh）， and pathological damage of lung tissue were observed in each group. Western blot and real-time PCR were employed to quantify the protein and mRNA levels， respectively， of high-temperature thermosensitive channels （TRPV1 and TRPV3） and low-temperature thermosensitive channels （TRPA1 and TRPM8） in the lung tissue. ResultsCompared with the blank group， the model group showed a typical asthma phenotype， including elevations in the level of EOS in peripheral blood， level of WBC in BALF， and value of Penh （P<0.05，P<0.01）， and severe lung tissue damage. Compared with the model group， the three formulas alleviated the asthma phenotype to varying degrees （P<0.05，P<0.01）. Compared with the blank group， the model group showed up-regulated protein levels of TRPV1 and TRPA1 in the lung tissue （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang groups showed down-regulated protein levels of TRPV1 and TRPA1 （P<0.05， P<0.01）. Moreover， Maxing Shigantang and Sanaotang groups showed more significant down-regulation in protein levels of TRPV1 and TRPA1， respectively （P<0.01）， while no obvious regulatory effect was observed in the Mahuangtang group. Compared with those in the blank group， the protein levels of TRPV3 and TRPM8 were up-regulated in the model group （P<0.01）. Compared with the model group， Maxing Shigantang and Sanaotang down-regulated the protein levels of TRPV3 and TRPM8 （P<0.01）. Moreover， Maxing Shigantang and Sanaotang exerted stronger down-regulating effects on TRPV3 （P<0.05） and TRPM8 （P<0.01）， respectively. Compared with the blank group， the model group presented up-regulated mRNA levels of TRPV1， TRPV3， TRPA1， and TRPM8 in the lung tissue （P<0.01）， and such up-regulations were significantly decreased by Maxing Shigantang and Sanaotang （P<0.01）. Moreover， Maxing Shigantang outperformed Sanaotang in regulating high-temperature thermosensitive channels TRPV1 and TRPV3 （P<0.05， P<0.01）. The regulation effect of the， Maxing Shigantang on high-temperature thermosensory channel proteins of TRPV1 and TRPV3 was better than that of the Sanaotang P<0.05P<0.01while the Sanaotang outperformedhad a significant regulatory effect on Maxing Shigantang in regulating the low-temperature thermosensory thermosensitive channel proteins of TRPA1 and TRPM8which was better than that of the Maxing Shigantang （P<0.05，P<0.01）. ConclusionThe experimental results showed that Mahuangtang， Sanaotang， and Maxing Shigantang all had protective effects on asthma airway inflammation.while Mahuangtang did not show the regulatory effect on TRPV1 and or TRPA1. Maxing Shigantang preferred to regulate high-temperature thermosensory thermosensitive channels of TRPV1 and TRPV3 channels， and Sanaotang preferred to regulate low-temperature thermosensory thermosensitive channels of TRPA1 and TRPM8.

Chronic heart failure （CHF） is a major global public health problem， and myocardial infarction is one of its main causes. The mouse model of heart failure induced by coronary artery ligation is widely used in the study of CHF， while the TCM syndrome attributes of this model have not yet been clarified. According to the theory of correspondence between prescriptions and syndromes， the method of syndrome identification by prescription efficacy is an important means of current syndrome research of animal models. This method deduces the syndrome characteristics of animal models through prescription efficacy. Taking the four basic syndrome elements of Qi， blood， Yin and Yang as the classification reference， this study used coronary artery ligation to construct a mouse model of CHF and treated the model with four representative TCM injections with the effects of replenishing Qi， warming Yang， nourishing Yin， and activating blood and enalapril. Echocardiography， tongue color parameters， histopathology， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and cardiac troponin Ⅰ （cTnⅠ） levels， and systematically explored the TCM syndrome attributes of this model. The results showed that the coronary ligation model presented an obvious cardiac function decline， myocardial fibrosis， infarct size expansion， and purple dark tongue， which were consistent with the basic syndrome characteristics of blood stasis in CHF. Danhong injection had significant effects of improving the cardiac function， alleviating myocardial fibrosis， and reducing serum NT-proBNP and cTnⅠ levels. Huangqi Injection and Shenfu injection can improve the cardiac function and tongue color parameters， with limited effects. The effect of Shenmai injection group was not obvious. This study verifies that the established model conforms to blood stasis syndrome through the method of syndrome identification by prescription efficacy， which provides an experimental basis for the study of TCM syndrome mechanism of CHF.

To explore the advantages of traditional Chinese medicine （TCM） and integrative TCM-Western medicine approaches in the treatment of diabetic microvascular complications （DMC）， refine key pathophysiological insights and treatment principles， and promote academic innovation and strategic research planning in the prevention and treatment of DMC. The 38th session of the Expert Salon on Diseases Responding Specifically to Traditional Chinese Medicine， hosted by the China Association of Chinese Medicine， was held in Beijing， 2024. Experts in TCM， Western medicine， and interdisciplinary fields convened to conduct a systematic discussion on the pathogenesis， diagnostic and treatment challenges， and mechanism research related to DMC， ultimately forming a consensus on key directions. Four major research recommendations were proposed. The first is addressing clinical bottlenecks in the prevention and control of DMC by optimizing TCM-based evidence evaluation systems. The second is refining TCM core pathogenesis across DMC stages and establishing corresponding "disease-pattern-time" framework. The third is innovating mechanism research strategies to facilitate a shift from holistic regulation to targeted intervention in TCM. The fourth is advancing interdisciplinary collaboration to enhance the role of TCM in new drug development， research prioritization， and guideline formulation. TCM and integrative approaches offer distinct advantages in managing DMC. With a focus on the diseases responding specifically to TCM， strengthening evidence-based support and mechanism interpretation and promoting the integration of clinical care and research innovation will provide strong momentum for the modernization of TCM and the advancement of national health strategies.

Functional dyspepsia （FD） is a prioritized disease category where traditional Chinese medicine （TCM） demonstrates distinct therapeutic advantages. The current western medicine treatment for FD is mainly based on proton pump inhibitors and prokinetic agents， with digestive enzymes， probiotics and antidepressants serving as adjuvant medication， yet such therapies still have certain limitations. TCM treatment for FD includes oral administration of Chinese herbal formulas and Chinese patent medicines， as well as external TCM therapies such as acupuncture and moxibustion， acupoint application， hot medicinal compress therapy， rubbing with ointment， medicinal iontophoresis， auricular acupoint therapy and tui na （Chinese medical massage）. The combined treatment of FD with integrated TCM and western medicine can significantly improve clinical effectiveness and reduce adverse reactions. The common mechanisms underlying the therapeutic effects of both TCM and western medicine revolve around the core pathological processes of FD， mainly focusing on restoring gastrointestinal motility， regulating the levels of brain-gut peptides， modulating intestinal microecology， and ameliorating inflammatory status. The differential mechanisms lie in the precise targeting feature of western medicine versus the holistic-regulating and multi-target characteristics of TCM， and the two approaches exert a synergistic effect to enhance efficacy. This paper proposes to leverage the advantages of TCM in holistic regulation and the strengths of western medicine in targeted treatment， so as to provide personalized and comprehensive treatment regimens for FD patients.

The common marmoset (Callithrix jacchus) is a species of the genus Callithrix in the primate family Callitrichidae. Common marmosets are an important scientific research resource for the study of neuroscience, medicine, and pharmacy. The feeding and breeding of common marmosets provide important support for scientific research. At present, common marmoset resources in China are at a critical stage of development. This paper takes the Center for Excellence in Brain Science and Intelligence Technology of the Chinese Academy of Sciences (hereafter referred to as CEBSIT) as an example to discuss the experience of common marmoset feeding, breeding and genetic management. In terms of breeding environment and facilities, on the basis of the national standard, more stringent environmental parameter standards are implemented for environmental temperature, relative humidity, the number of air exchanges, and the average concentration of sedimentation bacteria. Two kinds of cages for common marmoset breeding and experimentation are designed. According to the differences in facility conditions and staffing, a cleaning and maintenance method combining "dry rearing" and "wet rearing" is introduced. In terms of feeding management, in order to meet the high nutritional needs of common marmosets, CEBSIT prepares special formulated diets, and introduces the transition method of common marmosets from diets mixed with formulated rations and pellets to exclusive commercial diets, and strictly regulates the operation procedures of formulated diets for common marmosets, and has accumulated a series of methods for preventing nutritional and metabolic diseases in common marmosets. In terms of animal health management, the health of common marmosets is ensured through measures such as regular quarantine, isolation and treatment, and epidemic prevention, and the health inspection process of common marmosets is described in detail, and hierarchical and classified management is carried out according to the physical condition of common marmosets. This paper also briefly describes the treatment of diarrhea and pneumonia that are common in common marmosets. In terms of breeding management, it covers the selection of breeding common marmosets, combining pairs of common marmosets into the same cage for breeding, group splitting and hand-rearing of infant common marmosets, and introduces the method of reintroducing hand-reared infant common marmosets to parental care from the perspective of animal welfare. In terms of genetic management, the common marmoset population in CEBSIT is maintained as a closed colony and follows a non-inbreeding method. CEBSIT has developed an inbreeding screening system to check pedigree information before pairing to avoid inbreeding. Under conditions without introducing new individuals from outside, CEBSIT has continuously bred the colony for 5 generations while maintaining genetic heterozygosity. This paper only discusses the feeding, breeding and genetic management of the common marmoset and aims to provide a useful reference for other institutions engaged in common marmoset breeding.

ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.