ObjectiveTo explore the mechanism by which Xiaoyaosan regulates HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency by observing its effect on the glycoprotein hormone α-subunit （CGA）/glutathione peroxidase 2 （GPX2）/thyroid-stimulating hormone β-subunit （TSHβ） pathway for thyroid hormone synthesis. MethodsSeventy-two male SD rats were randomized into six groups： normal， model， high-dose （16.7 g·kg^-1）， medium-dose （8.35 g·kg^-1）， and low-dose （4.175 g·kg^-1） Xiaoyaosan， and fluoxetine （0.001 8 g·kg^-1） groups， with 12 rats in each group. The rat model of liver depression and spleen deficiency was induced by chronic restraint stress for 21 days. The intervention groups were treated with Xiaoyaosan decoctions or fluoxetine suspension， respectively. After modeling， hematoxylin-eosin staining was employed to observe morphological changes in the thyroid and pituitary tissue of the rats. Serum levels of triiodothyronine （T3）， tetraiodothyronine （T4）， and thyroid-stimulating hormone （TSH） were measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the mRNA and protein levels， respectively， of TSH receptor （TSHR） in the thyroid tissue， thyrotropin-releasing hormone receptor （TRHR） and TSHβ in the pituitary tissue， and thyrotropin-releasing hormone （TRH）， CGA， GPX2， and TSHβ in the hypothalamic tissue. ResultsCompared with the normal group， the model group showed significant atrophy and irregularity of thyroid follicles， a marked reduction in colloid secretion， extensive vacuolar degeneration of adenocytes in the anterior pituitary， lowered serum levels of T3， T4， and TSH （P<0.01）， and down-regulated mRNA and protein levels of TSHR in the thyroid tissue， TRHR and TSHβ in the pituitary tissue， and TRH， CGA， GPX2， and TSHβ in the hypothalamic tissue （P<0.01）. Compared with the model group， high- and medium-dose Xiaoyaosan and fluoxetine alleviated the pathological changes in the thyroid and pituitary tissue， outperforming the low-dose Xiaoyaosan group. Moreover， they elevated the serum levels of T3， T4， and TSH （P<0.05， P<0.01）. The serum TSH level was also elevated in the low-dose Xiaoyaosan group （P<0.05）. The mRNA and protein levels of TSHR in the thyroid， TRHR and TSHβ in the pituitary， and TRH， CGA， GPX2， and TSHβ in the hypothalamus were up-regulated in the high- and medium-dose Xiaoyaosan groups （P<0.05， P<0.01）. Additionally， the mRNA and protein levels of TSHβ in the hypothalamus were up-regulated in the low-dose Xiaoyaosan group （P<0.01）. In the fluoxetine group， the mRNA and protein levels of TSHR in the thyroid， TRHR in the pituitary， and TRH， CGA， and GPX2 in the hypothalamus were up-regulated （P<0.05， P<0.01）. ConclusionThe downregulation of CGA/GPX2/TSHβ pathway may be one of the biological mechanisms underlying HPT axis dysfunction in the rat model with the syndrome of liver depression and spleen deficiency. Xiaoyaosan may regulate the HPT axis dysfunction by up-regulating the CGA/GPX2/TSHβ pathway.

ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective: To analyze the serotypes and drug resistance of Salmonella isolated from food-borne disease surveillance samples in Longwan District, Wenzhou City, Zhejiang Province, so as to provide evidence for the prevention and treatment of Salmonella infection. Methods: Salmonella strains isolated from feces or anal swabs of patients with foodborne diarrhea in Longwan District People's Hospital from 2018 to 2024 were collected. After re-identification, slide agglutination test was used to identify serotypes. The drug susceptibility test of live Salmonella strains was performed using the broth microdilution method, and the resistance patterns were analyzed. Results: A total of 2 293 samples were collected, and 186 strains of Salmonella were isolated, with a detection rate of 8.11%. The detection rate was higher from May to October. A total of 28 Salmonella serotypes were identified, with S. typhimurium (72 isolates, 38.71%), S. enteritidis (31 isolates, 16.67%), and S. London (30 isolates, 16.13%) being dominant. Among the 121 Salmonella live strains, 20 strains were susceptible to 14 antibacterial drugs. A total of 101 strains were resistant to antibacterial drugs, and the drug resistance rate was 1.65%-67.77%, with the drug resistance rate of ampicillin being the highest, and the drug resistance rate of imipenem was the lowest. S. typhimurium had the highest resistance rate to tetracycline (78.26%). S. enteritidis had the highest resistance rate to ampicillin (100.00%). S. London had the highest resistance rate to tetracycline (66.67%). Fifty-five types of drug resistance patterns were detected, showing a number of drug resistance of 1-10, of which 76 strains were multi-drug resistant, accounting for 75.25%. The predominant multidrug resistance patterns were ampicillin/sulbactam-cefazolin-ampicillin-nalidixic acid (10.53%), tetracycline-ampicillin-nalidixic acid (9.21%), and ampicillin/sulbactam-ampicillin-nalidixic acid (7.89%). Conclusions Salmonella strains isolated from foodborne diseases in Longwan District were mainly detected in summer and autumn. S. typhimurium, S. enteritidis, and S. London were the predominant serotypes. The drug resistance of Salmonella to different antibacterial drugs was different, and the drug resistance spectrum showed diversity.

OBJECTIVE To investigate the selection strategy for recipient vessels in free flap reconstruction of head and neck defects.METHODS A retrospective analysis was conducted on 96 patients who underwent 99 free flap reconstructions for head and neck defects between January 2020 and December 2024.Recipient vessel selection,flap survival,and postoperative complications were analyzed based on defect location and flap type.RESULTS In 99 cases microvessel anastomosis,the recipient arteries were superior thyroid artery in 49 branches,facial artery in 28 branches,superficial temporal artery in 14 branches,lingual artery in 5 branches.external carotid artery in 1 branch,transverse cervical artery in 1 branch,and superior laryngeal artery in 1 branch.Venous anastomosis was performed in 104 branches,with 94 cases in 1 venous anastomosis and 5 cases in 2 venous anastomoses.The recipient veins selected were facial vein in 62 branches,external jugular vein in 21 branches,superficial temporal vein in 12 branches,retromandibular vein in 3 branches,middle thyroid vein in 2 branches,internal jugular vein in 2 branches,middle temporal vein in 1 branch,and superior thyroid vein in 1 branch.Complete flap necrosis occurred in 5 cases,and partial necrosis occurred in 4 cases.When the recipient vessels were deficient,the lingual artery was chosen in 3 cases,the facial artery in 1 case,the external jugular vein in 3 cases,the internal jugular vein with end-to-side anastomosis in 1 case,and the common facial vein with end-to-side anastomosis in 1 case.CONCLUSION In free flap reconstruction for head and neck defects,the superior thyroid artery,facial artery,and superficial temporal artery are commonly used as recipient arteries,while the facial vein,external jugular vein,and superficial temporal vein are frequently selected as recipient veins.When recipient vessels are scarce,the ipsilateral lingual artery,transverse cervical artery,and main trunk of the internal jugular vein can serve as alternative recipient vessels.

OBJECTIVE To systematically evaluate the repair strategies for temporal bone-parotid composite defects,compare the clinical applicability of local muscle flaps and free flaps,and provide references for optimizing the reconstruction of complex head and neck defects.METHODS We retrospectively analyzed the medical records of 17 patients with postoperative defects in the temporal bone-parotid region treated at Beijing Tongren Hospital,Capital Medical University,between January 2018 and June 2023.There were 11 males and 6 females,with a median age of 58 years(range:42-72 years).All patients had undergone radical resection.Defects were reconstructed with local flaps in 13 cases(temporalis muscle flap,n=6;sternocleidomastoid flap,n=3;submental platysma flap,n=2;submental island flap,n=2)and with free flaps in 4 cases(anterolateral thigh fascial flap,n=1;anterolateral thigh flap,n=1;free abdominal adipofascial flap,n=2).RESULTS The primary diseases of the 17 patients were malignant tumors of the external auditory canal and parotid gland(6 cases of squamous cell carcinoma,6 cases of adenoid cystic carcinoma,and 3 cases of ductal carcinoma).All flaps survived completely.One patient with temporalis muscle flap repair developed postoperative wound infection,which healed after debridement and dressing change.The median follow-up period was 16 months(4-29 months).Two cases(11.8%)of external auditory canal squamous cell carcinoma had local recurrence,one case(5.9%)of parotid ductal carcinoma developed pulmonary metastasis 9 months after surgery and died at 15 months.The remaining 14 cases(82.4%)were tumor-free survivors.Functional evaluation showed that the local tissue flap group had a shorter repair time,but was limited by muscle flap rotation arc;the free flap group could accurately match the defect shape,but the surgical time was prolonged to 3.5-4.5 hours.Fourteen cases(82.4%)received postoperative adjuvant radiotherapy.None of the tissue flaps developed radiation necrosis after radiotherapy.CONCLUSION Temporal bone-parotid composite defects need to balance the dual requirements of surgical cavity coverage and cosmetic repair.Local muscle flaps are easy to operate and have reliable blood supply,suitable for small and medium-sized defects;free tissue flaps have better shape adaptability in complex three-dimensional defect reconstruction,but require microsurgical technical support.The repair plan should be comprehensively decided based on the defect range,vascular conditions,and radiotherapy plan.The data of this group confirmed that both techniques can achieve stable therapeutic effects.

IgA nephropathy（IgAN）is the most common primary glomerular disease，characterized by the deposition of IgA in the glomerular mesangial area. IgAN is a progressive disease with a protracted and relapsing course. Approximately 50%~75% of adult IgAN patients experience renal function deterioration and eventually progress to end-stage kidney disease（ESKD）within 20 years after diagnosis. Among patients with onset in childhood，about 30% ultimately progress to ESKD after 20 years of long-term follow-up. In recent years，numerous studies have continuously explored important signaling pathways and key molecules in its pathogenesis. This review introduces the therapeutic advances in IgAN，aiming to provide better treatment options for clinicians.

Objective To investigate the serum interleukin-17A(IL-17A)and chemokine CXC motif ligand 13(CXCL13)levels in children with cough variant asthma and their clinical significance.Methods A total of 108 children with cough variant asthma admitted to Meihe Maternity Hospital from November 2021 to Febru-ary 2023 were selected as the study group,and 86 healthy children who underwent physical examinations dur-ing the same period were selected as the control group.The levels of serum IL-17A and CXCL13 in the two groups were detected by enzyme-linked immunosorbent assay.Multivariate Logistic regression was used to an-alyze the factors influencing the occurrence of cough variant asthma.Receiver operating characteristic(ROC)curve was plotted to analyze the diagnostic value of serum IL-17A and CXCL13 expressions for cough variant asthma.Results The levels of serum IL-17A and CXCL13 in the study group were both higher than those in the control group(P＜0.05).The levels of serum IL-17A and CXCL13 in children with cough variant asthma were negatively correlated with forced vital capacity(FVC),forced expiratory volume in one second(FEV1),maximal expiratory flow rate(PEF),and FEV1/FVC and basal respiratory conductivity(Grs cont),while positively correlated with initial resistance value(Rrs cont).Multivariate Logistic regression analysis indicated that FVC,FEV1,PEF,FEV1/FVC,and Grs cont were protective factors influencing the occurrence of cough variant asthma(P＜0.05).However,Rrs cont,IL-17A and CXCL13 were risk factors affecting the occurrence of cough variant asthma(P＜0.05).The area under the curve(AUC)of serum IL-17A and CXCL13 levels for diagnosing cough variant asthma were 0.920 and 0.867,respectively.The AUC of the combined diagnosis of the two was 0.937,which was significantly greater than that of the diagnosis of CXCL1 alone(Z=2.194,P=0.028).Conclusion The levels of serum IL-17A and CXCL13 in children with cough variant asthma are upreg-ulated,and both are related to the lung function and airway responsiveness of children with cough variant asthma.The combined detection of serum IL-17A and CXCL13 levels has a high diagnostic value for cough variant asthma.

Objective:To investigate the effects of carbon black and cadmium (Cd) combined exposure on autophagy and inflammatory response mediated by protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in human bronchial epithelial (16HBE) cells.Methods:In January 2022, human bronchial epithelial (16HBE) cells were resuscitated and cultured. Carbon black nanoparticles (CBNPs) were oxidized to adsorb Cd ions to construct "CBNPs-Cd" complexes. CCK-8 assay was used to detect the effects of different concentrations and time combinations of CBNPs and Cd on the viability of 16HBE cells. The subsequent dose groups were exposed to 2 μg/ml Cd, 100 μg/ml CBNPs, 100 μg/ml CBNPs+2 μg/ml Cd for 24 h. The number of autophagosomes and autolysosomes was detected by transmission electron microscopy. Western blotting was used to detect the protein expressions of PERK, eukaryotic initiation factor 2α (eIf2α), activating transcription factor 4 (ATF4), sequestosome 1 (SQSTM1/P62), and microtubule-associated protein 1 light chain 3 (LC3). After PERK gene was silenced by siRNA technology, the changes of autophagy marker proteins P62 and LC3 were detected, and the expressions of inflammatory factors interleukin-6 (IL6) and interleukin-8 (IL8) were detected by fluorescence quantitative PCR technique. One-way ANOVA analysis was used to compare three groups or more. LSD test was used for comparison between two groups. Factorial analysis was used for multivariate component analysis. Results:There was no significant change in cell viability of 16HBE after 24 h exposure to CBNPs and Cd alone or combined ( P>0.05). Compared with the control group, the expressions of P62 and LC3 in 16HBE cells were significantly increased in the CBNPs and Cd alone/combined exposure group ( P<0.05), and the number of autophagosomes and autophagolysosomes in the combined exposure group was increased compared with other groups. Compared with the control group, CBNPs and Cd alone exposure group had no significant effects on p-PERK/PERK and p-eIf2α/eIf2α protein expression ( P>0.05). However, the protein expressions of p-PERK/PERK and p-eIf2α/eIf2α and ATF4 were all increased in the combined exposure group ( P<0.05), and the levels of IL6 and IL8 in 16HBE cells in the combined exposure group of CBNPs and Cd were significantly higher than those in the control group ( P<0.05). The levels of LC3 protein, IL6 and IL8 were decreased in the CBNPs-Cd combined exposure group after knockdown of PERK gene ( P<0.05). The results of factorial analysis showed that exposure to CBNPs and Cd had significant effects on the expression of P62, LC3 and IL6 ( P<0.05), but the interaction between the two chemicals had no statistical significance ( P>0.05) . Conclusion:CBNPs-Cd combined exposure may inhibit autophagy and increase inflammation in human bronchial epithelial cells through activation of PERK-eIf2α-ATF4 pathway.

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.

Hemodynamics plays a vital role in the development and progression of cardiovascular diseases, and is closely associated with changes in morphology and function. Reliable detection of hemodynamic changes is essential to improve treatment strategies and enhance patient prognosis. The combination of computational fluid dynamics with cardiovascular imaging technology has extended the accessibility of hemodynamics. This review provides a comprehensive summary of recent developments in the application of computational fluid dynamics for cardiovascular hemodynamic assessment and a succinct discussion for potential future development.