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.

It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.

Objective To understand the respiratory protection competency of staff in hospitals.Methods Staff from six hospitals of different levels and characteristics in Beijing were selected,including doctors,nurses,medical technicians,and servicers,to conduct knowledge assessment on respiratory protection competency.According to exposure risks of respiratory infectious diseases,based on actual cases and daily work scenarios,content of respira-tory protection competency assessment was designed from three aspects:identification of respiratory infectious di-seases,transmission routes and corresponding protection requirements,as well as correct selection and use of masks.The assessment included 6,6,and 8 knowledge points respectively,with 20 knowledge points in total,all of which were choice questions.For multiple-choice questions,full marks,partial marks,and no mark were given respective-ly if all options were correct,partial options were correct and without incorrect options,and partial options were correct but with incorrect options.Difficulty and discrimination analyses on question of each knowledge point was conducted based on classical test theory.Results The respiratory protection competency knowledge assessment for 326 staff members at different risk levels in 6 hospitals showed that concerning the 20 knowledge points,more than 60％participants got full marks for 6 points,while the proportion of full marks for other questions was relatively low.Less than 10％participants got full marks for the following 5 knowledge points:types of airborne diseases,types of droplet-borne diseases,conventional measures for the prevention and control of healthcare-associated infec-tion with respiratory infectious diseases,indications for wearing respirators,and indications for wearing medical protective masks.Among the 20 knowledge questions,5,1,and 14 questions were relatively easy,medium,and difficult,respectively;6,1,4,and 9 questions were with discrimination levels of ≥0.4,0.30-0.39,0.20-0.29,and ≤0.19,respectively.Conclusion There is still much room for hospital staff to improve their respiratory protection competency,especially in the recognition of diseases with different transmission routes and the indications for wearing different types of masks.

Synthetic cannabinoids(SCs)are synthetic psychoactive substances that can pose a public health risk.The SCs are structurally variable and susceptible to structural modification.The rapid emergence of structurally unknown synthetic cannabinoids has led to new challenges in their identification.In recent years,machine learning has made great progress and has been widely applied to other fields,providing new strategies for the identification of unknown synthetic cannabinoids and the inference of possible sources.This paper describes the principles of commonly used machine learning methods and the application of machine learning techniques to mass spectrometry,Raman spectroscopy,metabolomics and quantitative conformational relationships of synthetic cannabinoids,aiming to provide new ideas for the identification of unknown synthetic cannabinoids.

[Objective]To investigate primary and secondary transfer of exfoliated cells from human hands on non-porous substrates such as plastic steering wheel or computer mouse.[Methods]DNA detection sensitivity and detection limit for mixed DNA profiling were examined to understand our laboratory's ability to test for trace DNA.Forensic swabs were used to collect samples from volunteers'one-hour-long unwashed hands,substrates touched by volunteers'immediately or 30 min following shaking hands,and individual A's daily-use substrates touched by individual B and then by individual A again.Simulations were conducted to assess the potential for introduction of another person's exfoliated cells from hands into routine casework samples.[Results]Our laboratory can obtain a full DNA profile from as little as 0.020 ng of DNA and detect minor components in a 1:9 mixed DNA sample.85%of samples from unwashed hands yielded a full DNA profile.Primary transfer of a full DNA profile was found in 77%of substrates touched by volunteers'dominant hand 30 min after hand washing,allowing differentiation between good and poor shedders,with no significant difference in genders and substrate types.75%of substrates touched 30 min after hand washing and then immediately following handshaking yielded the other individual's DNA profile(secondary transfer),with the number of short tandem repeat(STR)loci detected ranging from 0 to 23;the percentage and number decreased substantially when the substrates were touched 30 minutes later.No foreign DNA was detected in routine casework samples with introduced exfoliated cells from hands.When two individuals took turns touching items with their hands,the major contributor to the DNA profile was not always the individual who made the last contact.[Conclusions]Primary and secondary DNA transfer can be detected on non-porous substrates,and based on the deposit of hand exfoliated cells,individuals can be categorized as good or poor shedders,which is an important factor affecting detection of DNA transfer.Besides considering the laboratory's DNA detection sensitivity,if DNA is detected on substrates by hand contact,we need to take into account the potential for secondary transfer at different levels of activity when interpreting the results.

Yellow fever virus(YFV)is one of the most important mosquito-borne flaviviruses in the world,causing about 200,000 infections and 30,000 deaths each year,with serious impacts on human health and economic development.Currently,there are no approved specific anti-viral drugs for YFV infection.On the other hand,antibody drugs are safe,highly targeted and effective,making them one of the most effective means of prevention and treatment of viral infectious diseases.This review summarizes the characteristics of YFV and the recent advances in the development of protective antibodies against YFV,and predict the priorities of future research and development of protective antibodies,which may offer a new line of thought for subsequent development of yellow fever virus-specific drugs.

Objective:To evaluate the diagnostic performance of the Prostate Imaging Reporting and Data System version 2.1(PI-RADS v2.1)for clinically significant prostate cancer(CSPCa)in the peripheral zone(PZ),transitional zone(TZ)and multiple zones(MZs).Methods:We retrospectively studied the clinical data on 108 patients undergoing multiparametric magnetic resonance imaging(mpMRI)and transperineal prostate biopsy in our hospital from January 2021 to January 2023.Using PI-RADS v2.1,we ex-amined the MR images of the patients with suspected PCa,compared the PI-RADS v2.1 scores with the results of prostate biopsy,and analyzed the correlation of the PI-RADS v2.1 scores with CSPCa.We calculated the area under the receiver operating characteristic(ROC)curve(AUC),and described the diagnostic performance of PI-RADS v2.1 for CSPCa in the PZ,TZ and MZs.Results:Transperineal prostate puncture biopsy was successfully completed in all the patients,which revealed 66(61.11％)cases of CSPCa with Gleason score(GS)7-10.Suspected CSPCa was observed in 45(95.74％)of the 47 PZ lesions,8(47.06％)of the 17 TZ le-sions,and 40(90.91％)of the 44 MZ lesions.The PZ,TZ and MZ lesions diagnosed by PI-RADS v2.1 were significantly correlated with CSPCa(r=0.492,P＜0.001).The AUCs of PI-RADS v2.1 for PZ,TZ and MZs were 0.644,0.732 and 0.811,with specificities of 66.8％,57.6％and 62.1％,and sensitivities of 57.2％,78.4％and 93.2％,respectively.The negative predictive values were 46.5％,85.7％and 79.2％,and the positive predictive values 76.2％,43.4％and 84.8％,respectively.Conclusion:The PI-RADS v2.1 score has a high diagnostic value for CSPCa in the PZ,TZ and MZs,with the best performance for that in the MZs.

Abstract: Objective　To investigate the antimicrobial activity of omadacycline (OMC) against clinical Streptococcus agalactiae (GBS) isolates, as well as its relationship with biofilm formation, resistance genes and virulence genes. Methods　A total of 136 strains of Streptococcus agalactiae isolated from Shenzhen Nanshan People's Hospital between 2015 to 2020. The minimum inhibitory concentration (MIC) of OMC against Streptococcus agalactiae was determined by broth microdilution. Crystal violet staining was used to detect the biofilm formation ability of GBS. Resistance genes (tetM, tetO, tetK, ermB, OptrA) and virulence genes (cpsⅢ, bca, fbsA, cpsA, scpB) were investigated by polymerase chain reaction (PCR). Results　Among the 136 clinical isolates of GBS, 20 strains (14.7%) were resistant to OMC, 64 (47.1%) were intermediate, and 52 (38.2%) were sensitive. Fifty-seven strains (41.9%) were biofilm-positive, 20 of which (35.1%) were sensitive to OMC. Seventy-nine strains (58.1%) were biofilm-negative, 32 of which (40.5%) were susceptible to OMC. There was a statistically significant difference in the sensitivity rates between the two groups of strains (χ2=63.062, P<0.001), but there was no significant difference in the sensitivity of OMC among the biofilm-positive strains (Fisher's exact test, P=0.824). The resistance rates of tetM, tetO, ermB and OptrA positive strains were higher than those of negative strains, while tetK was opposite. The presence of tetM (Z=0.815, P=0.415), tetO (Z=0.151, P=0.88), tetK (Z=0.567, P=0.571), ermB (Z=1.198, P=0.231) resistance genes in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, the presence of the OptrA resistance gene showed a statistically significant effect on the sensitivity of OMC (Z=2.913, P=0.004). The virulence factors cpsⅢ, bca, fbsA, cpsA and scpB were all detected at a rate higher than 50%. The presence of the virulence genes cpsⅢ (Z=0.222, P=0.824), bca (Z=0.141, P=0.888), fbsA (Z=0.813, P=0.416), and cpsA (Z=1.615, P=0.106) in Streptococcus agalactiae had no significant impact on the sensitivity of OMC. However, there was a significant inter-group difference in the scpB virulence gene (Z=2.844, P=0.004), but the rank mean values and resistance rates of scpB-positive strains were lower than those of the negative strains. Conclusions　The formation of biofilm in Streptococcus agalactiae reduces its sensitivity to OMC, but there was no significant difference in the sensitivity to OMC among the biofilm-positive strains. The presence of resistance genes tetM, tetO, tetK, ermB, and virulence genes cpsⅢ, bca, fbsA, cpsA, scpB in Streptococcus agalactiae is not associated with OMC resistance, but the presence of the resistance gene OptrA is correlated with OMC resistance..

Objective To analyze and diagnose the chromosomal genetic etiology of male patients with azoospermia or oligozoospermia,and investigate the clinical application value of combined detection of chromosomal karyotype and Y-chromosome microdeletion in azoospermia or oligozoospermia.Methods The clinical data and peripheral blood samples of 240 male patients with azoospermia or oli-gospermia in Luzhou district of Sichuan were collected.The karyotype analysis of peripheral blood lymphocytes were analyzed by G-ban-ding in conventional chromosomal culture.Multiplex PCR technology was used to detect Y chromosome microdeletions.Results A-mong the 240 male patients with azoospermia or oligospermia,179 cases of azoospermia and 61 cases of severe oligospermia were found.The detection rate of chromosome karyotype abnormalities was 22.92％(55/240),including 30 cases of chromosome number abnor-malities,21 chromosome structure abnormalities and 4 combined abnormalities.The detection rate of Y chromosome microdeletion ab-normalities was 10.42％(25/240)with the highest deletion rate of 7.08％for AZFc abnormalities.The combined detection rate for the abnormalities of karyotype and Y chromosome microdeletion was 30.83％(74/240),among which 6 patients showed abnormalities in both detections.The detection rate of combined detections by the two methods was higher than that of single method(x2=30.24,P＜0.001).Conclusion This study systematically reported the incidence and types of karyotypes and Y chromosome microdeletions in male azoospermia or oligospermia patients in Luzhou district of Sichuan.We suggest that the combined application of the two methods may improve the detection rate of abnormality,which provides important guidance for the etiological diagnosis of male infertility pa-tients,genetic counseling and reproductive therapy.

Modern Traditional Chinese Medicine(TCM)physicians believed that"reproduction depends on the kidney"theory is the key in treating fetal leakage,fetal restlessness,slippery fetus and other diseases.However,before the Ming and Qing Dynasties,ancient physicians paid special attention to the theory of"Qi and blood in the spleen and stomach".The"the stem of fetal ties the spleen"came from the summary of Zhao Xianke's"Handan manuscripts"based on analogy of nature in Ming dynasty.However,at present,the relevant research reports on"spleen"and tocolysis are fragmented,and the theoretical traceability,clinical effects and experimental research are not systematically discussed.Based on the"fetal stem ties the spleen"theory,through integrated research,taking the differentiation of ancient and modern theories of traditional Chinese medicine gynecology as the"longitude",and the progress of modern biological research on"syndromes,prescriptions and components"as the"latitude".This study is an initial attempt to reveal the key inflection points deductively in the empty space(territorial schools)during(history and history of)tocolysis,and to systematically explore the"spleen main Qi","spleen main transportation","spleen main rising Qing"and"spleen main muscle",which are associated with the progress of the objectification and the bottleneck of research on the treatment of tocolysis.Furthermore,it is proposed that TCM prescription syndrome metabolism and spatiotemporal omics are the important trends to solve the disputes and difficulties in the study of tocolysis in the future,and provide a new reference idea for the inheritance,innovation,breakthrough and accurate research of modern TCM reproductive theory.