OBJECTIVE To explore the antidepressant mechanism of Wenyang jieyu granules （WYJYG） via the NOD-like receptor thermal protein domain associated protein 3 （NLRP3）/apoptosis-associated speck-like protein containing a CARD （ASC）/Caspase-1 pathway. METHODS A rat model of depression was established by chronic unpredictable mild stress combined with single-housing for 42 consecutive days.The experiment set up blank group， model group， MCC950 （NLRP3 inflammasome inhibitor） group （10 mg/kg）， fluoxetine group （positive control，2.08 mg/kg），low-dose WYJYG（3.78 g/kg） and high-dose WYJYG group （7.56 g/kg），with 10 rats in each group. From the 22nd day of the experiment， rats in the fluoxetine group， low-dose and high-dose WYJYG groups were intragastrically administered with the corresponding drugs and intraperitoneally injected with an equal volume of normal saline. Rats in the MCC950 group were intraperitoneally injected with MCC950 at the corresponding concentration and intragastrically administered with an equal volume of distilled water. Rats in the blank group and model group were given an equal volume of distilled water by gavage and an equal volume of normal saline by intraperitoneal injection. All interventions were performed once a day for 21 consecutive days. Behavioral tests were conducted once a week. After the last administration， the contents of ASC， ionized calcium binding adaptor molecule 1 （Iba1）， interleukin-1β （IL-1β）， and IL-18 in hippocampal tissues were detected. The protein expressions of NLRP3， cluster of differentiation 68 （CD68）， Caspase-1， B-cell lymphoma-2 （Bcl-2）， and Bcl-2-associated X protein were determined， and neuronal apoptosis was observed. RESULTS After the last administration， compared with the model group， the open-field activity time was significantly prolonged （ P ＜0.05）， and the latency to feed in a novel environment was significantly shortened （ P ＜0.05） in rats of the high-dose WYJYG group. In hippocampal tissue， the contents of ASC， Iba1， IL-1β， and IL-18， as well as the protein expression levels of NLRP3， Caspase-1， and CD68， and the positive rate of neuronal apoptosis were all significantly decreased/downregulated （ P ＜0.05）. Bcl-2 protein expression was significantly upregulated （ P ＜0.05）， and the density of neuronal apoptosis-positive cells was significantly reduced （ P ＜0.05）. CONCLUSIONS WYJYG play on antidepressant role by inhibiting the NLRP3/ASC/Caspase-1 pathway， reducing microglia-mediated neuroinflammation， and inhibiting hippocampal neurons apoptosis.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective:To observe any effect of oscillating positive expiratory pressure training on the airway clearing ability of postoperative esophageal cancer patients after neoadjuvant chemotherapy.Methods:Forty postoperative esophageal cancer patients undergoing neoadjuvant chemotherapy were enrolled and randomized into a control group and an experimental group, each of 20. Both groups received conventional postoperative rehabilitation starting on the first postoperative day, while the experimental group additionally underwent oscillating positive expiratory pressure training (3 sets/day, 30 breaths/set) for five consecutive days. Peak cough flow was measured using a peak flow meter before and 1, 3 and 5 days after the operation. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were also measured on the 5th day after the operation using spirometry. Any postoperative pulmonary complications were recorded.Results:On the 1st day after the operation, peak cough flow had decreased significantly in both groups compared to preoperative levels. However, it had increased significantly on days 3 and 5 in both groups, with the average increase in the experimental group significantly greater than in the control group. On day 5 the average FEV1, forced vital capacity and PEF in both groups were significantly lower than the preoperative values, while the experimental group demonstrated significantly higher average FEV1s (2.22±0.51L) and PEFs (5.09±1.26L/s) compared to the control group.Conclusions:Early postoperative oscillating positive expiratory pressure training can improve the peak cough flow and airway clearing ability of esophageal cancer patients after neoadjuvant chemotherapy, promoting the recovery of their lung function.

Objective To investigate the status of hearing impaired children's hearing device independence skills,and to explore the ways to improve their self-use of hearing equipment.Methods This study surveyed 64 re-habilitation teachers and 411 parents of children with hearing impairment aged 0-12 years.Through face-to-face or remote telephone interview,3 good habits(A asking parents for advice before removing the HA,B putting the de-vice into a moisture-proof box after removing it,C bringing batteries to school and knowing where are them)and 3 key abilities[D wearing the device independently,E replacing the battery independently,and F independently handle foreign bodies in the ear mold(Fa)and water vapor(Fb)]was investigated.The age when mastering skills or de-veloping habits difference of hearing impaired children in different groups were compared.Results ① The ratio of ability D in the bilateral CI group and the bilateral HA group of preschool children was 30.97％and 18.57％respec-tively.Among elementary school children,85.29％and 90.70％had this ability respectively.② The ratio of ability E in the bilateral CI group,the bilateral HA group and the bimodel group were 11.50％,15.71％and 16.49％,re-spectively.Among elementary school children,64.71％,53.49％and 68.52％had this ability,respectively.③Among preschool children,there was no statistical difference in age when different equipment groups developed the three good habits and acquired ability D and E(P＞0.05).④ Among primary school children,there was a statisti-cal difference in the age when different equipment groups formed habit A(P＜0.05),and the age when double CI group had this ability was slightly earlier than the double HA group.There was no significant difference in other abilities among age groups(P＞0.05).Conclusion The age at which hearing impaired children develop the three good habits precedes the age at which they master the key skills,which accords with the law of skill acquisition and development of ordinary children.Corresponding teaching process should be based on the age and ability of hearing-impaired children without considering the type of equipment.

Objective:To observe any effect of oscillating positive expiratory pressure training on the airway clearing ability of postoperative esophageal cancer patients after neoadjuvant chemotherapy.Methods:Forty postoperative esophageal cancer patients undergoing neoadjuvant chemotherapy were enrolled and randomized into a control group and an experimental group, each of 20. Both groups received conventional postoperative rehabilitation starting on the first postoperative day, while the experimental group additionally underwent oscillating positive expiratory pressure training (3 sets/day, 30 breaths/set) for five consecutive days. Peak cough flow was measured using a peak flow meter before and 1, 3 and 5 days after the operation. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF) were also measured on the 5th day after the operation using spirometry. Any postoperative pulmonary complications were recorded.Results:On the 1st day after the operation, peak cough flow had decreased significantly in both groups compared to preoperative levels. However, it had increased significantly on days 3 and 5 in both groups, with the average increase in the experimental group significantly greater than in the control group. On day 5 the average FEV1, forced vital capacity and PEF in both groups were significantly lower than the preoperative values, while the experimental group demonstrated significantly higher average FEV1s (2.22±0.51L) and PEFs (5.09±1.26L/s) compared to the control group.Conclusions:Early postoperative oscillating positive expiratory pressure training can improve the peak cough flow and airway clearing ability of esophageal cancer patients after neoadjuvant chemotherapy, promoting the recovery of their lung function.

Objective: To investigate the causal relationship between antioxidant nutrients and pregnancy complications, so as to provide the reference for the prevention and treatment of pregnancy complications. Methods: Data of seven antioxidant nutrients including vitamin A, vitamin C, vitamin E, selenium, zinc, copper and iron were collected from genome-wide association study (GWAS) Catalog database, and data of four pregnancy complications including gestational diabetes mellitus, pre-eclampsia, spontaneous abortion and preterm birth were collected from the Finland database. Single nucleotide polymorphism (SNP) data were collected, and 27 SNPS strongly correlated with seven antioxidant nutrients were selected as instrumental variables. Mendelian randomization (MR) analyses were performed using the inverse-variance weighted (IVW) method with seven antioxidant nutrients as exposures factors and four pregnancy complications as outcome variables. The heterogeneity was assessed using the Cochran's Q test, the horizontal pleiotropy was assessed using the MR-PRESSO test and MR-Egger regression, and the robustness of the results was verified with the leave-one-out. Results: Cochran's Q test showed heterogeneity of MR results between vitamin C and gestational diabetes mellitus, preeclampsia and preterm birth, between vitamin E and iron and gestational diabetes (all P<0.05), and a random effect model was employed. There was no heterogeneity in other results (all P>0.05), and a fixed effect model was employed. MR analysis results showed that there was no causal association between seven antioxidant nutrients and the risk of four pregnancy complications (all P>0.05). MR-PRESSO test and the MR-Egger regression identified no horizontal pleiotropy of instrumental variables (both P>0.05). Conclusion This study did not find genetically predicted associations of antioxidant nutrients with pregnancy complications.

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 analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.

Radiotherapy is one of the main treatment methods for malignant tumors, which can cause the radiation damage to normal tissues. Radiation-induced skin injury (RISI) is one of the main adverse reactions caused by radiotherapy. The main clinical manifestations of RISI are dermatitis, ulcer, erosion and necrosis, which seriously affect the quality of life and treatment effect of tumor radiotherapy patients, and even affect the overall survival of patients. The pathological mechanism of RISI is still unclear. Some studies have shown that inflammation and oxidative stress are the main causes of RISI. RISI can be divided into acute and chronic RISI according to the different onset time, and different treatment strategies can be formulated according to the severity of the injury. In this article, clinical manifestations, classification, pathogenesis, prevention and treatment of RISI are comprehensively summarized.

Objective To investigate the correlation of cerebral blood flow(CBF)after thrombolys-is with ischemia-reperfusion(I/R)injury and neurological function in patients with acute ischemic stroke(AIS).Methods Clinical data of 150 AIS patients admitted to our department from Febru-ary 2021 to February 2024 were collected and analyzed retrospectively.According to the changes in CBF in the affected side after thrombolysis,they were divided into hyperperfusion group(48 cases)and hypoperfusion group(102 cases).The condition of hemorrhagic transformation and perfusion parameters included CBF,cerebral blood volume(CBV),time to peak of residual func-tion(Tmax),mean transit time(MTT)and time to peak(TTP),and the relative values of regional cerebral blood flow(rCBF),rCBV,Tr,max,rMTT and rTTP.The general clinical data,oxidative stress,NIHSS score and inflammatory factor levels were compared between the two groups.Pear-son/Spearman correlation analysis was used to analyze the correlation between rCBF and oxida-tive stress,inflammatory factors,hemorrhagic transformation and NIHSS score in AIS patients after thrombolysis.Results In the hypoperfusion group,the MTT,Tmax and TTP values were sig-nificantly higher,and the CBF value was obviously lower in the affected side than the healthy side(P＜0.01).In hyperperfusion group,the MTT and TTP were notably lower,while the CBF and CBV were remarkably higher in the affected side than the healthy side(P＜0.01).The hypoperfu-sion group had significantly higher rMTT,Tr,max and rTTP,but lower rCBV and rCBF than the hyperperfusion group(P＜0.01).The levels of malondialdehyde(MDA),advanced oxidation pro-tein products,TNF-α and C-reactive protein(CRP)were significantly lower,and the level of su-peroxide dismutase(SOD)was higher in the hypoperfusion group than the hyperperfusion group(P＜0.05,P＜0.01).Pearson correlation analysis showed that rCBF was negatively correlated with MDA and TNF-α(r=-0.436,r=-0.451,P＜0.01)and positively correlated with SOD(r=0.412,P＜0.01).Conclusion The CBF changes after thrombolysis in AIS patients have a good correlation with I/R injury,but not with the recovery of neurological function.