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.

Objective: To explore the correlation among picky eating levels in preschool children, parental self-efficacy and parenting stress. Methods: A convenience sampling method was employed to conduct an electronic questionnaire survey among 459 children aged 3-6 years and their parents from five kindergartens in Urumqi in November 2023. The survey included a general information questionnaire, the Children s Eating Behavior Questionnaire (CEBQ), the Parenting Sense of Competence Scale (PSOC), and the Parenting Stress Index-Short Form (PSI-SF). The Mann-Whitney U-test was used for twogroup comparisons, and the Kruskal-Wallis H-test was applied for multi-group comparisons. Spearman correlation analysis was conducted to examine the relationships between children s picky eating levels and parenting selfefficacy as well as parenting stress. Results: The picky eating score of preschool children was 10.00 (4.00), and the parenting self-efficacy score was 58.00 (12.00), both indicating a moderate level. The parenting stress score was 75.00 (16.00), reflecting a moderately low level. Spearman correlation analysis showed that children s picky eating levels were negatively correlated with the total score of parenting self-efficacy ( r =-0.28) and positively correlated with the total score of parenting stress( r =0.25)( P <0.01). Conclusions Picky eating levels of preschool children are closely associated with parenting self-efficacy and parenting stress. Picky eating behaviors in children can be reduced by implementing various effective measures to enhance parenting self-efficacy and alleviate parenting stress.

Objective To understand the prevalence and risk factors of hyperuricemia in electronics factory workers in Wuhan, and to provide evidence for the health protection of electronics factory workers. Methods A total of 1 415 employees in an electronics factory in Wuhan were selected as the research subjects, and the physical examination and determination of various biochemical indicators, as well as questionnaire survey were carried out. Results The detection rate of hyperuricemia among workers in the electronics factory in Wuhan was 32.43%, with 36.33% for men and 14.11% for women, and the difference was statistically significant ( χ²＝46.077，P＜0.001). The detection rate of hyperuricemia was the highest (33.77%) among those with university or college education, followed by graduate students and above (31.50%). Compared with subjects with good lifestyle habits, people with drinking habits had higher hyperuricemia detection rate (49.38%), and the difference was statistically significant (P =0.001). The detection rates of hyperuricemia in those with central obesity and elevated alanine aminotransferase were 48.23% and 61.29%, respectively, which were significantly higher than those in the subjects without the above diseases (26.91% and 27.21%, respectively), and the differences were statistically significant (P <0.001). Obese people had the highest detection rate of hyperuricemia (66.95%), followed by overweight people (43.75%), and the difference was statistically significant (P <0.001). Multivariate logistic analysis showed that alcohol drinking (OR=1.836, 95% CI=1.139-2.961, P =0.013) and body mass index ≥ 24 kg/m² (OR=2.175, 95% CI=1.686 -2.806, P <0.001) were risk factors for hyperuricemia in electronic factory workers. Elevated alanine aminotransferase (ALT) was significantly correlated with hyperuricemia (OR=2.964, 95%CI=2.146-4.095 , P <0.001). Female gender was a protective factor for hyperuricemia in workers in the electronics factory (OR=0.441, 95%CI=0.297-0.653 , P <0.001). Conclusion The detection rate of hyperuricemia among workers in an electronics factory in Wuhan is high, and the detection rate of hyperuricemia in men is higher than that in women. Alcohol consumption, overweight and obesity will increase the risk of hyperuricemia. Elevated ALT is associated with hyperuricemia. Maintaining an ideal body mass index and establishing a good lifestyle play an important role in preventing hyperuricemia.

Objective The network pharmacological methods and molecular docking technology were used for investigating the possibility of Psoraleae Fructus in promoting precocious puberty in children and its potential mechanism.Methods The main active ingredients of Psoraleae Fructus and their therapeutic targets were obtained from BATMAN-TCM online platform.The disease targets related with precocious puberty were obtained from GeneCards database.A visualized network of active ingredients-disease targets was constructed by Cytoscape 3.7.1 software.Protein-protein interaction(PPI)network diagrams were constructed based on the STRING online database.Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted using Metascape online tool.The structures of the main active ingredients were obtained from PubChem database,the structures of core targets were obtained from RCSB PDB database,and then the structures were imported into Autodock for molecular docking.Finally,the mimic diagrams of the molecular docking were drawn using PYMOL software.Results A total of 12 active ingredients of Psoraleae Fructus were obtained,involving 274 targets.And there were 11 active ingredients and 98 targets associated with precocious puberty.The main active compounds were stigmasterol,bakuchiol,angelicin,bavachalcone,isobavachalcone,and xanthotoxin.The main targets were estrogen receptor 1(ESR1),estrogen receptor 2(ESR2),insulin-like growth factor 1(IGF1),and progesterone receptor(PGR),which were mainly involved in the ovarian steroidogenic pathway and Hippo signaling pathway.The molecular docking results showed that the active compounds were well binded to the targets.Conclusion It is possible that Psoraleae Fructus can promote the sexual development in children and has its potential pharmacological mechanism.The results will provide theoretical references for the clinical prevention and treatment of precocious puberty and early pubertal development in children.

Objective:To report the results of national surveillance on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2022.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of national bloodstream infection Bacterial Resistant Investigation Collaborative System（BRICS）were collected during January 2022 to December 2022. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 software were used to analyze the data.Results:During the study period，9 035 strains of Gram-negative bacteria were collected from 51 hospitals，of which 7 895（87.4%）were Enterobacteriaceae and 1 140（12.6%）were non-fermenting bacteria. The top 5 bacterial species were Escherichia coli（ n=4 510，49.9%）， Klebsiella pneumoniae（ n=2 340，25.9%）， Pseudomonas aeruginosa（ n=534，5.9%）， Acinetobacter baumannii complex（ n=405，4.5%）and Enterobacter cloacae（ n=327，3.6%）. The ESBLs-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus spp. were 47.1%（2 095/4 452），21.0%（427/2 033）and 41.1%（58/141），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（58/4 510）and 13.1%（307/2 340）；62.1%（36/58）and 9.8%（30/307）of CREC and CRKP were resistant to ceftazidime/avibactam combination，respectively. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 59.5%（241/405），while less than 5% of Acinetobacter baumannii complex was resistant to tigecycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 18.4%（98/534）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of main Gram-negative bacteria resistance among different regions，with statistically significant differences in the prevalence of CRKP and CRPA（ χ2=20.489 and 20.252， P<0.001）. The prevalence of CREC，CRKP，CRPA，CRAB，ESBLs-producing Escherichia coli and Klebsiella pneumoniae were higher in provinicial hospitals than those in municipal hospitals（ χ2=11.953，81.183，10.404，5.915，12.415 and 6.459， P<0.01 or <0.05），while the prevalence of CRPA was higher in economically developed regions（per capita GDP ≥ 92 059 Yuan）than that in economically less-developed regions（per capita GDP <92 059 Yuan）（ χ2=6.240， P=0.012）. Conclusions:The proportion of Gram-negative bacteria in bloodstream infections shows an increasing trend，and Escherichia coli is ranked in the top，while the trend of CRKP decreases continuously with time. Decreasing trends are noted in ESBLs-producing Escherichia coli and Klebsiella pneumoniae. Low prevalence of carbapenem resistance in Escherichia coli and high prevalence in CRAB complex have been observed. The composition ratio and antibacterial spectrum of bloodstream infections in different regions of China are slightly different，and the proportion of main drug resistant bacteria in provincial hospitals is higher than those in municipal hospitals.

Objective:To assess the applicability of fully automatic pipeline automated testing for internal quality control (automated quality control).Methods:Stability, assay efficiency and implementation costs of 18 biochemical tests, 5 immunoturbidimetric tests and 11 chemical illuminescent tests in the Department of Laboratory Medicine of Peking Union Hospital from January 2019 to July 2022 were evaluated using automated quality control implementation methods. The detailed method is as follows: quality control materials for biochemical, immunoturbidimetric and chemiluminescent tests were stored in the refrigerator in the pipeline which was controlled by the intermediate software, and were automatically retrieved and tested as pre-set followed by documenting and storing. The quality control setup for the biochemical tests included refreshing quality control materials daily and weekly,both of which were paralleled for 3 months. The on-line storage stability of quality control materials in the pipeline was evaluated by comparing the coefficients of variation ( CV) of the quality control results between the two patterns. Effect of automated quality control application was evaluated using 6 indicators, including the results′ variation of automatically performed and manually performed quality controls, the out-of-controlled rate, the consumption of quality control materials, the change of staff workload, the impact on the testing time of the first sample, and the failure rate of automated quality control. Results:(1) Storage stability of quality control materials in the pipeline: under the pattern of weekly refresh of the biochemical quality control materials, except for total carbon dioxide (TCO 2) (the CVs of low and high level quality control were respectively 20.24% and 21.82%) and sodium (the CV of low level quality control was 1.51%) that were greater than the allowable variation set by the laboratory, the CVs of the rest tests meet the lab requirements on the allowable variations. (2) The results′ variation of quality control in automatically performed and manually performed control patterns: in the patterns of daily refresh of biochemical quality control materials and weekly refresh of immunoturbidimetric and chemiluminescent quality control materials, the CVs of both low and high levels of quality control were lower in the automatically performed control pattern than that in manually performed pattern for 8 chemiluminescent items of dehydroepiandrosterone sulfate, estradiol, follicle stimulating hormone, luteinizing hormone, serum ferritin, serum folic acid, vitamin B12 and testosterone, 3 immunologic items of complement 3, C reactive protein and immunoglobulin G, and 10 biochemical items of alkaline phosphatase, glucose, calcium, chloride, potassium, lactate dehydrogenase, sodium, urea, low density lipoprotein cholesterol, and adenosine deaminase. The out-of-control rates of biochemistry, immunoturbidimetric and chemiluminescence tests in both quality control patterns conformed with the clinical routine work requirements. (3) Comparison of quality control materials′ consumption: compared with manually performed quality control, weekly consumption of automatically performed chemiluminescent quality control materials decreased 37.5% (from 8 ml to 5 ml); weekly consumption of automatically performed immunoturbidimetric quality control materials decreased 33.3% (from 3 ml to 2 ml). (4)Comparison of staff workload and first sample testing time: compared with manually performed quality control, automatical quality control reduced manual work by about 156 steps per week, and the daily initial testing time was earlier by 15 min on average. The failure rate was 54.5% (37/64) during the early-stage application of the automated quality control which dropped to 10.2% (13/128) in the late-stage. Conclusion:The results of automated quality control detected in the pipeline system meet the quality indicators′ requirements of the laboratory, and the application of automated quality control can improve the quality control, save costs, reduce workload, and improve work efficiency.

The Ehlers-Danlos syndrome(EDS)is a rare inherent connective tissue disorder.The prev-alence of EDS in the population is estimated at one out of ten thousand to one out of a hundred thousand.The vascular EDS(vEDS)are rare among the subtypes but are the worst in prognosis.The article reports a case of vEDS admitted to the hospital.The patient was a young man complaining of a sudden onset of aphasia in right hemiparalysis and severe left abdominal pain for unknown reasons.The diagnosis was made after the genetic testing.The patient suffered from vEDS.Then,the multi-disciplinary team(MDT)made a treatment plan tailored to this young patient.The complexity in classification and delusive presentations of the EDS make the correct diagnosis very challenging.This article hopes to report this case and to share the experiences to the bet-ter understanding of this disease.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

S100 calc-binding protein A8/A9(S100A8/A9)can induce the migration of primary tumor cells to distant target organs by binding multiple channel proteins,promote the formation of tumor metastasis microenvironment,and play an important role in the immune and inflammatory response of the body.It provides a new target and idea for the prevention and treatment of tumor metastasis and invasion.This paper mainly reviewed the expression and mechanism of S100A8/A9 on related channel proteins in a variety of high incidence tumors,in order to provide a new strategy for tumor prevention,diagnosis and treatment.

Objective To observe the clinical efficacy and safety of rituximab injection in the treatment of patients with phospholipase A2 receptor-associated membranous nephropathy(PLA2R-MN).Methods The PLA2R-MN patients were randomly divided into control group and treatment group.The control group received oral prednisone tablets,initial dose of 40-60 mg·d-1,gradually reduced the dose according to the patients'condition after 2 months,cyclophosphamide injection 0.6 g per time,intravenous infusion,once every 2 weeks,for 6 consecutive times,then adjusted to 1.0 g per time,intravenous infusion,once a month;the treatment group received 375 mg·m-2 rituximab injection intravenous infusion,once a week,for 4 consecutive weeks,on the basis of the control group treatment.Both groups of patients were treated for 6 months.The clinical efficacy,24 h urine protein quantification,serum creatinine(SCr),glomerular filtration rate(eGFR),urinary microalbumin(UAlb),urinary creatinine(UCr)and adverse drug reactions were compared between two groups.Results Fifty-three patients were enrolled in the treatment group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.Fifty-three patients were enrolled in the control group,2 cases dropped out,and 51 cases were finally included in the statistical analysis.After treatment,the total effective rate of the treatment group and the control group were 92.16％(47 cases/51 cases)and 76.47％(39 cases/51 cases),and the difference was statistically significant(P＜0.05).After treatment,the 24 h urine protein quantification of the treatment and control groups were(0.86±0.30)and(1.04±0.27)g·24 h-1;SCr levels were(103.37±18.80)and(120.55±19.94)μmol·L-1;eGFR levels were(65.89±8.17)and(55.87±9.36)mL·min-1·1.73 m-2;UAlb levels were(47.45±13.52)and(98.21±25.50)mg·L-1;UCr were(1.55±0.42)and(1.96±0.51)mg·g-1,respectively,and the differences were all statistically significant(all P＜0.05).The adverse drug reactions of two groups were mainly nausea,vomiting,liver function damage,skin itching,infection,hair loss,etc.The total incidences of adverse drug reactions in the treatment and control groups were 43.14％and 37.25％,without significant difference(P＞0.05).Conclusion Rituximab injection has a definite clinical efficacy in the treatment of PLA2R-MN patients,which can significantly improve the renal function of patients,and does not increase the incidence of adverse drug reactions.