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.

BACKGROUND: Atrial fibrillation (AF) is a common cardiac arrhythmia in the elderly. This study aimed to evaluate urban-rural disparities in its prevalence and management in elderly Chinese. METHODS: Consecutive participants aged ≥ 65 years attending outpatient clinics were enrolled for AF screening using handheld single-lead electrocardiogram (ECG) from April 2017 to December 2022. Each ECG rhythm strip was reviewed from the research team. AF or uninterpretable single-lead ECGs were referred for 12-lead ECG. Primary study outcome comparison was between rural and urban areas for the prevalence of AF. The Student's t-test was used to compare mean values of clinical characteristics between rural and urban participants, while the Pearson's chi-square test was used to compare between-group proportions. Multivariate stepwise logistic regression analysis was performed to estimate the association between AF and various patient characteristics. RESULTS: The 29,166 study participants included 13,253 men (45.4%) and had a mean age of 72.2 years. The 7073 rural participants differed significantly (P ≤ 0.02) from the 22,093 urban participants in several major characteristics, such as older age, greater body mass index, and so on. The overall prevalence of AF was 4.6% (n = 1347). AF was more prevalent in 7073 rural participants than 22,093 urban participants (5.6% vs. 4.3%, P < 0.01), before and after adjustment for age, body mass index, blood pressure, pulse rate, cigarette smoking, alcohol consumption and prior medical history. Multivariate logistic regression analysis identified overweight/obesity (OR = 1.35, 95% CI: 1.17-1.54) in urban areas and cigarette smoking (OR = 1.62, 95% CI: 1.20-2.17) and alcohol consumption (OR = 1.42, 95% CI: 1.04-1.93) in rural areas as specific risk factors for prevalent AF. In patients with known AF in urban areas (n = 781) and rural areas (n = 338), 60.6% and 45.9%, respectively, received AF treatment (P < 0.01), and only 22.4% and 17.2%, respectively, received anticoagulation therapy (P = 0.05). CONCLUSIONS In China, there are urban-rural disparities in AF in the elderly, with a higher prevalence and worse management in rural areas than urban areas. Our study findings provide insight for health policymakers to consider urban-rural disparity in the prevention and treatment of AF.

International registration of herbal drugs is a necessary prerequisite for the internationalization of Chinese materia medica. North America and European Union occupy an important position in the world herbal drugs market, and their drug administration and quality supervision requirements are relatively complete and progressiveness. By summarizing the definition of herbal drugs in North America and European Union, combing and interpreting the relevant laws, regulations and policy documents, this article constructed the registration path of herbal drugs, and discussed the current status of market registration of herbal drugs in North America and European Union based on the examples of successful marketing of herbal drugs under current application and approval in overseas markets. This article believed that in the future, an internationally matched TCM quality standard evidence system should be built, clinical trials of TCM products in line with international standards should be carried out, standards that are the same or higher than international mainstream GMP should be developed, the registration path of TCM compounds should be explored, and professionals to establish an international registration application team should be recruited to provide theoretical and practical support for China's overseas registration of Chinese TCM products, promote TCM products to enter the world mainstream market, and achieve high-quality development of TCM internationalization.

Based on the view of the correspondence between nature and man in traditional Chinese medicine TCM),TCM master Professor Xia Guicheng attaches importance to the transformation of yin and yang in the female reproductive rhythm and created the"menstrual cycle rhythm regulation method".Women's special physiological phenomena are manifested in the periodic rhythm.The bi-ological clock is the internal mechanism for producing and regulating the physiological behavior and laws of organisms.The biological clock gene is widely expressed in ovarian granulosa cells,theca cells and corpus luteum cells,and is involved in the synthesis of ster-oid hormones,differentiation of follicular somatic cells,follicle development and ovulation and other physiological processes,playing an important role in female reproductive endocrine.Circadian rhythm disorders can lead to reproductive diseases such as menstrual disor-ders,ovarian dysfunction,and endocrine metabolic disorders.There are similarities between TCM time medicine and the biological clock rhythm system.Fully understanding the impact of the biological clock on female ovarian function,revealing its scientific connota-tion,and clarifying the regulatory method and mechanism will have a positive role in resisting reproductive disorders and optimizing fer-tility.

Objective To explore the ideas,methods and pathways for the registration of Chinese medicine prescriptions in overseas countries,to form a strategy for overseas registration of Chinese medicine,and to provide technical support and reference for China's Chinese medicine prescriptions to go abroad.Methods Five representative countries were selected to form corresponding expert teams and exchange platforms for international cooperation.The laws,regulations,rules,standards,specifications and technical guidance documents related to Chinese medicine prescription preparations of the target countries were used as pathway research materials,and the documents were translated directly,naturalized,proofread and diagrammed,and a problem-oriented mechanism for consultation with domestic and international experts was established to form a pathway for overseas registration of Chinese medicine prescription preparations.Results The path for standardization of overseas registration of Chinese medicines was clarified,and the detailed registration paths and corresponding work strategies of Chinese medicines in five countries were formulated with flow charts,tables and explanatory texts.Conclusion By developing standardized registration pathways for traditional Chinese medicine in target countries,reference can be provided for the internationalization of Chinese herbal formula preparations.

Introduces the regulatory requirements of the Natural and Over-the-Counter Health Products Administration on the quality of natural health products, and adopts the literature research method to translate and interpret Health Canada's "Guidelines for the Quality of Natural Health Products" on the quality management and quality control of natural health products. Policy documents, from the perspective of stakeholders, provide requirements for the detection methods and standards of natural health products, such as characterization, identification experiments, component content, pollutants and impurity content detection, etc. To achieve natural health Quality management and quality control in the whole process of product production. Familiar with and understand the requirements for the quality management of natural health products in Canada will help to promote the legal and compliant management of product quality in the production process of Traditional Chinese Medicine (TCM) products after registration in Canada, and promote the production and sustainable development of TCM products. At the same time, it provides a reference for further improving my country's drug quality management system normative system documents, and assists the effective connection between the registration-related standards of Chinese patent medicines and international standards.

Abstract: Objective To compare the diagnostic efficacy of the upgraded version of the GeneXpert automated fluorescent quantitative PCR system (GeneXpert MTB/RIF Ultra, GeneXpert Ultra) and the original version of the GeneXpert system (GeneXpert MTB/RIF, Xpert), real-time fluorescent quantitative nucleic acid detection (FQ-PCR), real-time fluorescent thermostatic amplification of Mycobacterium tuberculosis RNA (SAT-RNA), real-time fluorescent thermostatic amplification detection of DNA (thermostatic amplification method) and traditional BACTEC MGIT 960 liquid culture (culture method) for special specimens of tuberculosis, in order to analyze its application value in clinical detection. Methods Using prospective research methods, a total of 170 special specimens (including 47 pleural and ascites effusion samples, and 34 24-hour urinary sediment specimens, 49 tissue specimens and 40 fester specimens) were collected i'an Chest Hospital from January to September 2021. GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were used for detection. Clinical diagnosis was used as the standard, and sensitivity, specificity, positive predictive value, negative predictive value, coincidence rate, and Kappa value were compared among the methods. Results The sensitivities of GeneXpert Ultra, Xpert, FQ-PCR, SAT-RNA, isothermal amplification, and traditional culture were 65.18% (73/112), 49.11% (55/112), 37.50% (42/112), 19.64% (22/112), 8.04% (9/112), and 22.32% (25/112), respectively. The sensitivity of GeneXpert Ultra was higher than that of the other five methods, and the differences were statistically significant (χ2=66.25, 42.10, 28.89, 13.09, 4.92, 15.18, all P<0.05). GeneXpert Ultra result analysis showed that: 5.48%(4/73) cases had trace, that is, trace Mycobacterium tuberculosis load, 79.45% (58/73) cases were extremely low, 10.96% (8/73) cases were low, 2.74% (2/73) were medium, , and 1.36% (1/73) were high load. In 4 trace samples, the Xpert detection was negative for all. Of the 73 GeneXpert Ultra positive reports, 63 were rifampicin-sensitive, 6 were rifampicin-resistant, and 4 were rifampicin-resistant but of unclear resistance. Of the 55 Xpert positive reports, 45 were rifampicin-sensitive, 2 were rifampicin-resistant, and 8 were rifampicinresistant but of unclear resistance.. Conclusions The new generation of GeneXpert MTB/RIF Ultra has high sensitivity, specificity and drug resistance detection rate, and its advantage is even more apparent in the pathogenic diagnosis of special specimens of tuberculosis. It can be used as one of the preferred methods in samples with low bacterial load.

OBJECTIVES: To investigate the risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture and establish a nomogram model for predicting the risk of neonatal asphyxia. METHODS: A retrospective study was conducted with 613 cases of neonatal asphyxia treated in 20 cooperative hospitals in Enshi Tujia and Miao Autonomous Prefecture from January to December 2019 as the asphyxia group, and 988 randomly selected non-asphyxia neonates born and admitted to the neonatology department of these hospitals during the same period as the control group. Univariate and multivariate analyses were used to identify risk factors for neonatal asphyxia. R software (4.2.2) was used to establish a nomogram model. Receiver operator characteristic curve, calibration curve, and decision curve analysis were used to assess the discrimination, calibration, and clinical usefulness of the model for predicting the risk of neonatal asphyxia, respectively. RESULTS: Multivariate logistic regression analysis showed that minority (Tujia), male sex, premature birth, congenital malformations, abnormal fetal position, intrauterine distress, maternal occupation as a farmer, education level below high school, fewer than 9 prenatal check-ups, threatened abortion, abnormal umbilical cord, abnormal amniotic fluid, placenta previa, abruptio placentae, emergency caesarean section, and assisted delivery were independent risk factors for neonatal asphyxia (P<0.05). The area under the curve of the model for predicting the risk of neonatal asphyxia based on these risk factors was 0.748 (95%CI: 0.723-0.772). The calibration curve indicated high accuracy of the model for predicting the risk of neonatal asphyxia. The decision curve analysis showed that the model could provide a higher net benefit for neonates at risk of asphyxia. CONCLUSIONS The risk factors for neonatal asphyxia in Hubei Enshi Tujia and Miao Autonomous Prefecture are multifactorial, and the nomogram model based on these factors has good value in predicting the risk of neonatal asphyxia, which can help clinicians identify neonates at high risk of asphyxia early, and reduce the incidence of neonatal asphyxia.
Infant, Newborn ; Humans ; Male ; Pregnancy ; Female ; Nomograms ; Retrospective Studies ; Cesarean Section ; Risk Factors ; Asphyxia Neonatorum/etiology*

BACKGROUND: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images. METHODS: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists. RESULTS: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%). CONCLUSIONS: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists. TRIAL REGISTRATION Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
Area Under Curve ; Breast/diagnostic imaging* ; Breast Neoplasms/diagnostic imaging* ; China ; Deep Learning ; Humans ; ROC Curve ; Sensitivity and Specificity

Objective:Through phosphatidylinositol 3-kinase（PI3K）/protein kinase B （Akt）/mammalian rapamycin target protein （mTOR） signaling pathway， explore the effect of Zhigancao Tang on myocardial ischemia-reperfusion injury（MIRI）The role and mechanism of arrhythmia（ventricular tachycardia and ventricular fibrillation）. Method:The 72 SD rats were randomly divided into sham operation group，model group， Zhigancao Tang low，medium and high dose group（11.43，22.86，45.72 g·kg^-1），Wenxin granule group（2.43 g·kg^-1），continuous drug intervention for 10 days. Two hours after the last administration，the MIRI model of rat was prepared by ligating the left anterior descending coronary artery，and the changes of electrocardiogram were recorded. After successful modeling，blood and heart tissue were collected to detect the content of creatine creatine（CK），lactate dehydrogenase（LDH）and aspartate aminotransferase（AST）in the serum, the enzyme-linked immunoassay（ELISA） method was used to detect cardiac troponin（CtnI）content, immunohistochemical detection of myocardial PI3K，Akt，mTOR expression. Western blot was used to detect the myocardial autophagy-related protein microtubule-associated protein 1 light chain 3（LC-3），autophagy markers Beclin1 and PI3K/Akt/mTOR signaling pathway related protein expression and phosphorylated p-PI3K，p-Akt，p-mTOR levels. Result:In model group， 100% of ventricular tachycardia and 91.67% of ventricular fibrillation occurred. Compared with sham operation group， the serum levels of CK，LDH，AST，and CtnI in the model group were significantly increased（P<0.01），PI3K，Akt，mTOR AOD values in myocardial tissue were significantly increased （P<0.01），the relative expression of the ratio of LC3-Ⅱ/LC3-Ⅰ and Beclin1 was significantly increased（P<0.01），p-PI3K/PI3K，p-Akt/Akt，and p-mTOR/mTOR were significantly reduced （P<0.01）. Compared with model group， the incidence of ventricular tachycardia and ventricular fibrillation in the high-dose Zhigancao Tang group was significantly reduced （P<0.01），and the duration was the shortest compared with other administration groups（P<0.01）， CK，LDH，AST level and CtnI content were significantly reduced（P<0.01）， the expression of PI3K，Akt and mTOR of Zhigancao Tang group was significantly decreased with increasing dose（P<0.01）， the expression of LC-3 and Beclin1 was accompanied by Zhigancao Tang increase of each dose group of soup had different degrees of decrease （P<0.01），while the expression ratio of PI3K/Akt/mTOR-related protein was significantly increased （P<0.05，P<0.01）. Conclusion:Pretreatment of Zhigancao Tang can reduce the abusually elevated cardiac enzymes CK, LDH, AST and CtnI, inhibit excessive autophagy of cells, and up-regulate the expression of PI3K, Akt and mTOR, indicating that the anti-MIRI arrhythmia effect of Zhigancao Tang may be related to the PI3K/Akt/mTOR signaling pathway.