Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

ObjectiveTo observe the clinical efficacy and safety of Tangning Tongluo tablets in the treatment of nonproliferative diabetic retinopathy （DR）. MethodsFourteen research centers participated in this study， which spanned a time interval from September 2021 to May 2023. A total of 240 patients with nonproliferative DR were included and randomly assigned into an observation group （120 cases） and a control group （120 cases）. The observation group was treated with Tangning Tongluo tablets， and the control group with calcium dobesilate capsules. Both groups were treated for 24 consecutive weeks. The vision， DR progression rate， retinal microhemangioma， hemorrhage area， exudation area， glycosylated hemoglobin （HbA1c） level， and TCM syndrome score were assessed before and after treatment， and the safety was observed. ResultsThe vision changed in both groups after treatment （P<0.05）， and the observation group showed higher best corrected visual acuity （BCVA） than the control group （P<0.05）. The DR progression was slow with similar rates in the two groups. The fundus hemorrhage area and exudation area did not change significantly after treatment in both groups， while the observation group outperformed the control group in reducing the fundus hemorrhage area and exudation area. There was no significant difference in the number of microhemangiomas between the two groups before treatment. After treatment， the number of microhemangiomas decreased in both the observation group （Z=-1.437， P<0.05） and the control group （Z=-2.238， P<0.05）， and it showed no significant difference between the two groups. As the treatment time prolonged， the number of microhemangiomas gradually decreased in both groups. There was no significant difference in the HbA1c level between the two groups before treatment. After treatment， the decline in the HbA1c level showed no significant difference between the two groups. The TCM syndrome score did not have a statistically significant difference between the two groups before treatment. After treatment， neither the TCM syndrome score nor the response rate had significant difference between the two groups. With the extension of the treatment time， both groups showed amelioration of TCM syndrome compared with the baseline. ConclusionTangning Tongluo tablets are safe and effective in the treatment of nonproliferative DR， being capable of improving vision and reducing hemorrhage and exudation in the fundus.

Objective:To study the current status of longitudinal extrauterine growth restriction (EUGR) in extremely preterm infants (EPIs) and to develop a prediction model based on clinical data from multiple NICUs.Methods:From January 2017 to December 2018, EPIs admitted to 32 NICUs in North China were retrospectively studied. Their general conditions, nutritional support, complications during hospitalization and weight changes were reviewed. Weight loss between birth and discharge > 1SD was defined as longitudinal EUGR. The EPIs were assigned into longitudinal EUGR group and non-EUGR group and their nutritional support and weight changes were compared. The EPIs were randomly assigned into the training dataset and the validation dataset with a ratio of 7∶3. Univariate Cox regression analysis and multiple regression analysis were used in the training dataset to select the independent predictive factors. The best-fitting Nomogram model predicting longitudinal EUGR was established based on Akaike Information Criterion. The model was evaluated for discrimination efficacy, calibration and clinical decision curve analysis.Results:A total of 436 EPIs were included in this study, with a mean gestational age of (26.9±0.9) weeks and a birth weight of (989±171) g. The incidence of longitudinal EUGR was 82.3%(359/436). Seven variables (birth weight Z-score, weight loss, weight growth velocity, the proportion of breast milk ≥75% within 3 d before discharge, invasive mechanical ventilation ≥7 d, maternal antenatal corticosteroids use and bronchopulmonary dysplasia) were selected to establish the prediction model. The area under the receiver operating characteristic curve of the training dataset and the validation dataset were 0.870 (95% CI 0.820-0.920) and 0.879 (95% CI 0.815-0.942), suggesting good discrimination efficacy. The calibration curve indicated a good fit of the model ( P>0.05). The decision curve analysis showed positive net benefits at all thresholds. Conclusions:Currently, EPIs have a high incidence of longitudinal EUGR. The prediction model is helpful for early identification and intervention for EPIs with higher risks of longitudinal EUGR. It is necessary to expand the sample size and conduct prospective studies to optimize and validate the prediction model in the future.

Objective:To study influence of cardiac rehabilitation exercise combined nutritional intervention on pa-tients with acute myocardial infarction(AMI)after percutaneous coronary intervention(PCI).Methods:A total of 100 AMI patients treated in our hospital were randomly and equally divided into routine nursing group and combined intervention group(received cardiac rehabilitation exercise combined nutritional intervention mode based on routine nursing group)according to random number table method.Both groups were intervened for two months.General clinical data,anaerobic threshold(AT),maximal oxygen uptake(VO2peak),LVEF,6min walking distance(6MWD),scores of China questionnaire of quality of life in patients with cardiovascular diseases(CQQC)and gen-eral self-efficacy scale(GSES)before and after intervention and incidence rate of cardiovascular adverse events within three months were compared between two groups.Results:Compared with routine nursing group,after inter-vention,there were significant rise in AT[(10.14±2.81)ml·kg-1·min-1 vs.(14.85±3.80)ml·kg-1· min-1],VO2peak[(1.23±0.40)ml·kg-1·min-1 vs.(2.44±0.46)ml·kg-1·min-1],LVEF[(48.96± 3.73)％vs.(55.98±4.31)％],6MWD[(300.72±33.71)m vs.(340.47±31.86)m],scores of CQQC[(53.59 ±6.28)scores vs.(72.93±7.15)scores]and GSES[(21.21±2.39)scores vs.(32.28±5.44)scores]in com-bined intervention group(P=0.001 all).Incidence rate of cardiovascular adverse events in combine intervention group within three months was significantly lower than that of routine nursing group(10.0％vs.48.0％,P=0.001).Conclusion:Cardiac rehabilitation exercise combined nutritional intervention can observably improve quality of life,cardiopulmonary function,enhance self-efficacy and reduce incidence rate of adverse cardiovascular events in patients with acute myocardial infarction after percutaneous coronary intervention.

The pathogenesis of diabetic cardiomyopathy(DCM)is complex.Autophagy plays a pivotal role in the development of DCM,and whether its level is stable or not is closely related to the development of the course of DCM.Numerous active components found in traditional Chinese medicines and compound formulations have demonstrated the ability to modulate autophagy levels.These interventions occur through various mechanisms,such as hypoglycemic,anti-apoptotic,anti-inflammatory,and anti-oxidative stress pathways.By mitigating autophagy-induced myocardial damage,enhancing cardiac function,and slowing the progression of DCM,these compounds offer promising avenues for DCM management.This paper aims to consolidate and present research findings from the last 5 years.Our goal is to provide valuable insights and references for the research,development,and clinical application of Chinese medicine in the context of combating DCM.

AIM To establish an HPLC method for the simultaneous content determination of gallic acid,protocatechuic acid,morroniside,loganin,sweroside,paeoniflorin,hypericin,astragalin,salvianolic acid B,salvianolic acid A,epimedin C and icariin in Bushen Huoxue Sanjie Capsules.METHODS The analysis was performed on a 30℃thermostatic Agilent 5 TC-C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelength was set at 240 nm.RESULTS Twelve constituents showed good linear relationships within their own ranges(r≥0.999 8),whose average recoveries were 97.11%-101.14%with the RSDs of 0.60%-2.65%.CONCLUSION This simple,accurate and reproducible method can be used for the quality control of Bushen Huoxue Sanjie Capsules.

Objective This study aimed to investigate the potential relationship between urinary metals copper (Cu), arsenic (As), strontium (Sr), barium (Ba), iron (Fe), lead (Pb) and manganese (Mn) and grip strength. Methods We used linear regression models, quantile g-computation and Bayesian kernel machine regression (BKMR) to assess the relationship between metals and grip strength.Results In the multimetal linear regression, Cu (β=-2.119), As (β=-1.318), Sr (β=-2.480), Ba (β=0.781), Fe (β= 1.130) and Mn (β=-0.404) were significantly correlated with grip strength (P < 0.05). The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was -1.007 (95％ confidence interval:-1.362, -0.652; P < 0.001) when each quartile of the mixture of the seven metals was increased. Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength, with Cu, As and Sr being negatively associated with grip strength levels. In the total population, potential interactions were observed between As and Mn and between Cu and Mn (Pinteractions of 0.003 and 0.018, respectively).Conclusion In summary, this study suggests that combined exposure to metal mixtures is negatively associated with grip strength. Cu, Sr and As were negatively correlated with grip strength levels, and there were potential interactions between As and Mn and between Cu and Mn.

Objective To understand the research status,hotspots and trends of Wuzhuyu Decoction;To provide reference for relevant research.Methods The literature related to Wuzhuyu Decoction was retrieved from CNKI,VIP,Wanfang Data and CBM databases from the establishment to February 28,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,organization and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 822 articles were included,and the number of publications showed a wave upward trend;the top journals were New Chinese Medicine,Henan Traditional Chinese Medicine and Sichuan Traditional Chinese Medicine;the main research institutions were Beijing University of Chinese Medicine,China Academy of Chinese Medical Sciences and Shandong University of Traditional Chinese Medicine;a total of 566 authors were involved,and the authors with more publications included Wang Zhimin(12),Gong Muxin(9)and Bi Kaishun(5);high-frequency keywords included"headache","Shang Han Lun","TCM therapy"and so on.Conclusion Wuzhuyu Decoction is effective in treating chronic gastritis,hypertension and other primary diseases,which is a research hotspot in this field.It is a research trend in this field to explore its active components by high performance liquid chromatography and explain its action mechanism and target at the molecular level.

Objective To understand the research status,hotspots and trends of animal medicinal materials;To provide reference for future research.Methods The literature related to animal medicinal materials was retrieved from CNKI,VIP,Wanfang Data and CBM from January 1,2000 to April 30,2023.NoteExpress 3.6 was used to merge and deduplicate,and the author,institution and keywords were mapped and interpreted by CiteSpace 6.1.R6 software.Results A total of 1 169 articles were included,and the overall publication quantity in this field showed a stable fluctuation trend;the top journals were Lishizhen Medicine and Materia Medica Research,China Journal of Chinese Materia Medica and Modern Chinese Medicine;the main research institutions were China Academy of Chinese Medical Sciences,Changchun University of Chinese Medicine and Chinese Academy of Medical Sciences;a total of 676 authors were involved,and the authors with more publications included Zhang Hui(22),Liu Rui(15),Lin Zhe and Ma Shuangcheng(14);high-frequency keywords included"identification","TCM resources","clinical application"and so on.Conclusion Resource survey of animal medicinal materials,standardized breeding of medicinal animals,development of alternatives to rare medicinal animal resources,and construction of quality standard system for animal medicinal materials are the research hotspots in this field.The basic research of pharmacodynamic substances of animal medicinal materials based on the integrated analysis strategies of proteomics,peptideomics and transcriptomics,and the revelation of the signaling pathways and targets of animal medicinal materials from the molecular biology level are the research trends in this field.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.