ObjectiveTo establish a quality evaluation method for Zhuye Shigao granules（Zhuye Shigaotang） based on fingerprint and determination of index components， and to investigate the therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome. MethodsThe fingerprint of Zhuye Shigao granules was established by high performance liquid chromatography（HPLC）， and the methods for determination of total calcium， orientin， isoorientin， ginsenosides Rg₁， Re and Rb₁ and other 2 index components were established. Fifty ICR mice were randomly divided into the blank group， model group， Zhuye Shigao granules low， medium and high dose groups（9.3， 18.6， 37.2 g·kg^-1·d^-1）， with 10 mice in each group. In addition to the blank group， the model mice with cold-dampness pestilence attacking lung syndrome was prepared by nasal drip of lipopolysaccharide combined with cold-dampness environment. Each administration group was given the corresponding liquid by gavage according to the dose， while the blank group and model group were given the same volume of normal saline by gavage. Then， the body temperature and organ index of mice in each group were measured， hematoxylin-eosin（HE） staining was used to investigate the lung tissue injury of mice in each group， and enzyme-linked immunosorbent assay（ELISA） was used to detect the changes of tumor necrosis factor-α（TNF-α）， interleukin（IL）-lβ， IL-6， IL-10 levels in serum and lung tissue， as well as immunoglobulin（Ig）A and IgM levels in serum. ResultsThe fingerprint similarity of 10 batches of Zhuye Shigao granules was>0.950， and 20 common peaks were calibrated. Seven of them were identified， including peak 11（isoorientin）， peak 12（orientin）， peak 14（apioside liquiritin）， peak 15（liquiritin）， peak 17（apioside isoliquiritin）， peak 19（isoliquiritin） and peak 20（liquiritigenin）. The results of quantitative analysis showed that the content range of each index component in 10 batches of Zhuye Shigao granules was as follows：Total calcium of 9.978-11.294 mg·g^-1， isoorientin of 0.033-0.041 mg·g^-1， orientin of 0.046-0.055 mg·g^-1， ginsenoside Rg₁+ginsenoside Re of 0.748-0.762 mg·g^-1， ginsenoside Rb₁ of 0.151-0.197 mg·g^-1， liquiritin of 1.106-1.366 mg·g^-1， glycyrrhizic acid of 0.904-1.182 mg·g^-1_. Compared with the blank group， the body temperature of mice in the model group was significantly increased， the organ indexes of liver， lung and spleen were significantly decreased， the organ index of thymus was significantly increased， HE staining of lung tissue showed infiltration of inflammatory cells， a small amount of serous exudation was observed in the alveoli， and lung tissue was damaged. After the intervention of Zhuye Shigao granules， the pathological changes were improved compared with the model group. The expression levels of IL-1β， IL-6 and TNF-α were significantly increased， the expression level of IL-10 was significantly decreased in serum and lung tissue. The levels of IgA and IgM in serum were significantly decreased（P<0.01）. Compared with the model group， the body temperature， the organ indexes and immune factor levels in serum and lung tissue of mice in the Zhuye Shigao granules medium and high dose groups were significantly reduced（P<0.05， P<0.01）. ConclusionIn this study， the quality evaluation of Zhuye Shigao granules was carried out based on fingerprint combined with determination of index components， and the fingerprint of four herbs（Lophatheri Herba， Ophiopogonis Radix， Pinelliae Rhizoma and Glycyrrhizae Radix et Rhizoma） in this formula and the determination of 8 index components were established. The therapeutic effect of Zhuye Shigao granules on mice with cold-dampness pestilence attacking lung syndrome may be related to inhibiting inflammatory response and mediating immune regulation.

Pemphigus vulgaris (PV) is the most common subtype of pemphigus. It predominantly affects adults, with pediatric cases being exceedingly rare. Despite advancements in clinical treatment, the mortality rate of pediatric PV (PPV) has historically been alarmingly high, ranging from 70% to 100% in the absence of proper diagnosis and treatment. Although recent improvements in therapeutic strategies have led to a gradual decline in mortality, early and appropriate intervention remains crucial, particularly for children with acute onset and rapid disease progression, to prevent severe complications. However, due to the rarity of PPV, no standardized diagnostic and treatment guidelines are currently available. This study retrospectively analyzed 104 PPV cases recorded in the PubMed and China National Knowledge Infrastructure (CNKI) databases between 1969 and 2024, with the aim of providing insights for the standardized diagnosis and management of PPV. PPV presents with flaccid blisters affecting both cutaneous and mucosal surfaces. Upon rupture, these blisters result in painful, sharply demarcated erythematous erosions, accounting for approximately 1.4%-3.7% of all reported PV cases. The age of onset ranges from 1.5 to 18 years, with an average of 12.4 years, and no significant gender differences have been observed. In pediatric patients, the oral mucosa is typically the earliest and most frequently affected site, with an involvement rate as high as 87.3%, and it most commonly affects the buccal mucosa (27.9%). Other mucosal sites are affected in 52.9% of cases, with genital (28.8%) and perianal (6.7%) involvement being more frequent than in adult patients. Skin lesions are present in 80.4% of pediatric cases, a significantly higher rate than 16.0%-68.4% observed in adults. If lesions are relatively localized, local glucocorticoid therapy can be attempted first, with 8.3% of children achieving complete remission through local treatment alone. Systemic glucocorticoid therapy is the preferred option for cases that respond poorly to local therapy. Among these cases, 75.3% of pediatric patients were treated with prednisone, with 85.1% starting at an oral dose of 0.5-1.5 mg/kg/day, while 14.9% received an initial dose of 2 mg/kg/day. Alternative treatments, such as immunosuppressants, biologics, or other adjuvant medications, may be considered for pediatric patients who exhibit an inadequate response to glucocorticoid therapy or experience severe adverse effects. The most commonly used agents include azathioprine (24.0%), dapsone (21.7%), and rituximab (12.5%). The follow-up period for pediatric patients ranged from 1 to 120 months, with an average duration of 38 months. Prognosis in pediatric patients was more favorable compared to adults, with 43.8% achieving complete remission (cessation of treatment), 37.5% achieving partial remission (low-dose maintenance therapy), 9.6% still undergoing treatment, and only 1.1% succumbing to pneumonia or sepsis. Compared to adults, prolonged corticosteroid use in children poses a greater risk to physiological and psychological well-being, making them more susceptible to adverse effects related to growth, metabolism, and ocular health. Severe adverse reactions occurred in 22.1% of pediatric patients receiving corticosteroids, with Cushingoid facies (73.9%) and weight gain (39.1%) being the most common. In addition, 30.4% experienced growth and skeletal abnormalities, including growth retardation (17.4%), osteoporosis (8.7%), and fractures (4.3%). While PPV shares certain etiological, clinical, and histopathological characteristics with adult PV (APV), early diagnosis and timely intervention remain critical for optimal outcomes. Multidisciplinary collaboration is often necessary to ensure comprehensive management, improve treatment adherence, and safeguard the physical and psychological health of pediatric patients.

ObjectiveTo clarify the neuroprotective effect of black Panacis Quinquefolii Radix（PQR） and explore its active ingredients， with the aim of establishing an activity-oriented quality evaluation method. MethodsTransgenic Tg（HuC∶EGFP） zebrafish was used to establish a neuronal injury model by aluminum chloride immersion. Different doses（10， 20 mg·L^-1） of PQR and black PQR ethanol extracts were administered. The neuroprotective effects of PQR and black PQR were compared by analyzing the fluorescent area and intensity of zebrafish neurons. Based on ultra-performance liquid chromatography（UPLC）， a fingerprint profile of black PQR was established， followed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. Differential components were screened using the criteria of variable importance in the projection（VIP） value>1 and P<0.05. The neuroprotective activity of 14 batches of black PQR was assessed， and Spearman correlation analysis was used to identify saponins related to neuroprotective activity， which were then validated. Based on the above results， active marker components were determined， and an UPLC method was established for their quantitation with clear content limits. ResultsPharmacological efficacy results showed that both PQR and black PQR at different doses could significantly improved neuronal damage in zebrafish. At a dose of 20 mg·L^-1， black PQR demonstrated superior efficacy（P<0.05）. The fingerprint similarities of 14 batches of black PQR were>0.94， with 26 common peaks identified. Through comparison with the reference standards， 8 components were confirmed， including peak 1（ginsenoside Rg₁）， peak 2（ginsenoside Re）， peak 5（ginsenoside Rb₁）， peak 9（ginsenoside Rd）， peak 16［ginsenoside 20（S）-Rg₃］， peak 17［ginsenoside 20（R）-Rg₃］， peak 18（ginsenoside Rk₁）， and peak 19（ginsenoside Rg₅）. The results of PCA and OPLS-DA indicated that there were differences in saponins among black PQR samples from different origins， and 12 differential components were screened. All 14 batches of black PQR exhibited good protective effects on zebrafish neurons， with Shaanxi-produced black PQR showing superior protective effects compared to the other three production regions. Spearman correlation analysis revealed that a total of 11 components， including ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅， showed a significant positive correlation with the neuroprotective effect in zebrafish（P<0.05）. The activity validation results indicated that ginsenosides 20（S）-Rg₃， 20（R）-Rg₃， Rk₁ and Rg₅ were the primary components responsible for the neuroprotective effects of black PQR. Quantitative analysis showed that the content of ginsenoside 20（S）-Rg₃ in 14 batches of black PQR ranged from 0.17% to 0.52%， and the repair rate of neuronal damage ranged from 42.77% to 97.83%. ConclusionBased on the fingerprint and neuronal protective activity， the spectrum-effect related quality control model of black PQR was established， with ginsenoside 20（S）-Rg₃ as the quality control index， and the neuronal damage repair rate≥60% as the evaluation standard， the minimum limit of ginsenoside 20（S）-Rg₃ in black PQR should be≥0.20%.

Objective:To investigate the correlation between the level of treponema pallidum specific antibodies(TPAb)and immunoglobulin A/E/M/G(IgA/E/M/G)and IgG subtypes in active syphilis patients,so as to provide a basis for the comprehensive di-agnosis and treatment and prognosis evaluation of clinical syphilis.Methods:Active syphilis patients admitted to the First Affiliated Hospital of Soochow University in 2023 were divided into 1∶4+and 1∶16+groups according to the syphilis toluidine red unheated se-rum test(TRUST),and healthy control group were selected for the detection of TPAb by chemiluminescence microparticle immunoas-say(CMIA).The contents of IgA/E/M/G and IgG1/2/3/4 were determined by immunoturbidimetry.Results:A total of 206 patients with active syphilis(125 males and 81 females)aged(46.05±19.58)years were included in this study.Compared with the healthy control group,IgG2 was decreased and TPAb,IgA/E/M/G and IgG1/3/4 levels were increased in the active syphilis group,with statistically significant differences in TPAb,IgE and IgG1/2/3 levels(P<0.05).Compared with the healthy control group,TRUST 1∶4+group had statistical differences in TPAb,IgE and IgG2,and TPAb was significantly correlated with IgE and IgG2/4.The levels of TPAb,IgA/E/M/G and IgG1/2/3 in TRUST 1∶16+group were statistically significant,and TPAb was significantly correlated with IgE and IgG4(P<0.05).In addition,there were significant differences in TPAb,IgG and IgG1/3 between the two positive groups(P<0.05).Conclu-sion:The levels of TPAb and Ig in active syphilis patients with different TRUST titers are significantly different.TPAb combined with Ig can be used to monitor the strength of syphilis activity,IgA/M/G and IgG1/3 may be candidate biomarkers.

Objective:To investigate the relationship between basic psychological needs satisfaction, family resilience and psychological resilience with self-neglect in older adults on maintenance hemodialysis, and to analyze the mediating effect of family resilience and psychological resilience between basic psychological needs satisfaction and self-neglect.Methods:The social demographic questionnaire, basic psychological needs satisfaction scale, the Connor-Davidson resilience scale 10-item, family resilience questionnaire and scale of the elderly self-neglect were applied to 623 older adults on maintenance hemodialysis randomized sampled from 50 hemodialysis centers in Hunan Province from July to December 2021. The data were statistically described and mediated pathway analysis was performed using SPSS 28.0 and AMOS 24.0.Results:The scores of basic psychological needs satisfaction, psychological resilience, family resilience and elderly self-neglect in older adults on maintenance hemodialysis were (4.95±1.01), (23.24±8.19), (78.60±12.49) and (7.99±5.60), respectively.Correlation analysis showed that self-neglect was statistically negatively correlated with basic psychological needs satisfaction, psychological resilience and family resilience ( r=-0.398, -0.419, -0.451, all P<0.001), basic psychological needs satisfaction was positively correlated with resilience and family resilience ( r=0.594, 0.534, both P<0.001), and psychological resilience was positively correlated with family resilience ( r=0.477, P<0.001).Analysis psychological of mediation effects showed that basic psychological needs satisfaction had a total effect of -0.462 on self-neglect. The direct effect was -0.113, accounting for 25% of the total effect. The mediating effects of family resilience and psychological resilience were -0.189 and -0.122 respectively, accounted for 41% and 26% of the total effect. The chain mediating effect was -0.038, with an effect size of 8%. Conclusion:Basic psychological needs satisfaction for older adults on maintenance hemodialysis can affect self-neglect either directly or indirectly through family resilience and psychological resilience, and self-neglect can be reduced in the future by increasing family resilience and psychological resilience through meeting the basic psychological needs of older adults on maintenance hemodialysis.

Objective:To investigate the diagnostic value of 3.0T magnetic resonance with high b-value diffusion weighted imaging (DWI) for endometrial carcinoma (EC).Methods:The clinical data of 118 patients with suspected endometrial lesions were analyzed retrospectively. Among them, 83 cases were pathologically diagnosed as EC (EC group), and 35 cases were diagnosed as complex or atypical hyperplasia (endometrial hyperplasia group). In addition, 47 patients with normal endometrial (normal endometrial group) in the same period were selected. All patients underwent 3.0T MRI conventional T 2-weighted imaging (T 2WI) and multiple b-value (0, 300, 400, 600, 800, 1 000, 2 000, 3 000 and 4 000 s/mm 2) DWI scans. The endometrial signal intensity on different b-value DWI was measured. The b-value-endometrial signal intensity curve was drawn, and the decline degree of endometrial signal intensity was calculated. Results:When b-value was 300, 400, 600 and 800 s/mm 2, there was no significant difference in endometrial signal intensity among the three groups ( P>0.05); when b-value was 1 000, 2 000, 3 000 and 4 000 s/mm 2, the signal intensity in EC group was significantly higher than that in normal endometrial group and endometrial hyperplasia group (456.1 ± 119.4 vs. 371.3 ± 99.9 and 381.6 ± 184.8, 284.2 ± 91.9 vs. 163.2 ± 46.5 and 191.4 ± 110.8, 196.7 ± 72.4 vs. 103.7 ± 30.9 and 129.4 ± 83.1, 151.6 ± 54.8 vs. 74.6 ± 20.8 and 101.1 ± 60.7), and there was statistical difference ( P<0.05); while there was no significant difference between normal endometrial group and endometrial hyperplasia group ( P>0.05). The results of b-value-endometrial signal intensity curve showed that the decrease of endometrial signal intensity in EC group was significantly lower than that in normal endometrial group and endometrial hyperplasia group (0.79 ± 0.05 vs. 0.90 ± 0.03 and 0.87 ± 0.04), the index in endometrial hyperplasia group was significantly lower than that in normal endometrial group, and there was statistical difference ( P<0.05). Conclusions:High b-value DWI is useful for the differentiation of benign and malignant endometrial lesions, and it can improve the qualitative diagnostic value of EC.

The stimulator of interferon genes(STING),an integral adaptor protein in the DNA-sensing pathway,plays a pivotal role in the innate immune response against infections.Additionally,it presents a valuable therapeutic target for infectious diseases and cancer.We observed that fangchinoline(Fan),a bis-benzylisoquinoline alkaloid(BBA),effectively impedes the replication of vesicular stomatitis virus(VSV),encephalomyocarditis virus(EMCV),influenza A virus(H1 N1),and herpes simplex virus-1(HSV-1)in vitro.Fan treatment significantly reduced the viral load,attenuated tissue inflammation,and improved survival in a viral sepsis mouse model.Mechanistically,Fan activates the antiviral response in a STING-dependent manner,leading to increased expression of interferon(1FN)and interferon-stimulated genes(ISGs)for potent antiviral effects in vivo and in vitro.Notably,Fan interacts with STING,preventing its degradation and thereby extending the activation of IFN-based antiviral responses.Collectively,our findings highlight the potential of Fan,which elicits antiviral immunity by suppressing STING degra-dation,as a promising candidate for antiviral therapy.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Objective To identify the differentially expressed genes and pathways of bone marrow-derived mast cells(BMMCs)of mice induced by IL-3 and IL-3+stem cell factor(SCF)using bioinformatics analysis,which may provide a foundation for in vitro culture and functional study of mast cells(MC).Methods The matrix data of GSE35332 dataset in IL-3 and IL-3+SCF induced BMMCs was downloaded from the GEO database,and the R software was applied to screen differentially expressed genes(DEGs).The gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of EDGs were performed based on the online tool DAVID database.The protein interaction network was constructed by STRING database and hub genes were screened through MCODE plugin of the Cytoscape software.Results The GSE35332 data set was analyzed by R software,and 1 339 DEGs were screened,including 723 up-regulated genes and 616 down-regulated genes.A total of 6 hub genes were screened through the MCODE plugin of Cytoscape software,namely Psmd8,Psmd6,Psmd14,Psmc4,Psma6 and Psma3.GO and KEGG analysis showed that the hub genes were concentrated in proteolysis,antigen processing and presentation of exogenous peptide antigen via MHC class I,proteasome-mediated ubiquitin-dependent protein catabolism process,and Epstein-Barr virus infection.Conclusion This study found that there were significant differences in BMMCs gene expression profiles in mice induced by two modes and 6 hub genes participated in ubiquitin-dependent protein decomposition process through bioinformatics based on the GEO database,providing help for further research on MC vitro culture and function.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).