Background Prenatal chronic psychological stress may increase the risk of allergic diseases in children, and eczema is the most common allergic disease in children, the pathogenesis of which is not yet fully understood. Objective To preliminarily clarify the changes in offspring intestinal flora after chronic stress exposure during pregnancy in rats that increases offspring immune imbalance and eczema susceptibility. Methods Thirty SPF-grade adult female SD rats were selected and randomly divided into a model group and a control group (n=15). Sixteen male rats were randomly divided into a model mating group and a control mating group (n=8). A 28-day chronic unpredictable mild stress (CUMS) model during pregnancy was established. On the 7th day of stress, male and female rats were caged in a ratio of 3:1. Blood samples were collected from female rats in each group via angular vein on the 1st day before stress, and on the 7th, 14th, 21st, and 28th days after stress. The content of plasma corticosterone during pregnancy was determined by enzyme-linked immunosorbent assay (ELISA). For the offspring rats, an eczema model was constructed using 2,4-dinitrochlorobenzene (DNCB). The number of scratching times of the offspring rats within 5 min was recorded. The offspring rats were divided into 4 groups: DNCB-CUMS group (MM), DNCB-control group (MC), solvent control-CUMS group (CM), and blank control group (CC), with 8 rats in each group. The eczema was induced once every 3 days, and the induction period was 12 d. The expression level of immunoglobulin E (IgE) in the serum of offspring rats after the eczema induction experiment were determined by ELISA. The concentrations of tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin-2 (IL-2), interleukin-4 (IL-4), and interleukin-13 (IL-13) in the serum were quantified by multi-parameter flow cytometry. The composition and abundance of intestinal microbiota in the feces of offspring rats were detected by 16S rRNA high-throughput sequencing technology. Results The plasma corticosterone concentrations in the model group were higher than those in the control group on the 7th and 21st days of stress (P<0.05). On the 14th and 21st days of stress, the 1% sucrose preference percentages of female rats in the model group were lower than that in the control group. On the 7th, 14th, and 21st days of stress, the horizontal movement scores of female rats in the model group and the vertical movement scores on the 7th and 14th days were lower than those in the control group (P<0.05). After 6, 9, and 12 d of model building, the scratching frequencies in the MC group and MM group were significantly higher than those in the CC group and CM group (P<0.05). Moreover, there were differences in the contents of cytokines including IFN-γ, IL-2, TNF-α, IL-4, IL-13, and IgE among the offspring rat groups (P<0.05). The CM group and MM group led to an increase in the contents of TNF-α, IL-4, IL-13, and IgE cytokines (P<0.05), while the MM group caused a decrease in the contents of IFN-γ and IL-2 (P<0.05). After the eczema induction experiment, the α-diversity analysis showed that the Simpson index and Shannon index in the CM were higher than those in the CC (P<0.05), indicating that CUMS during the pregnancy of female rats could increase the species abundance of their offspring. The abundances of Prevotella and Lactobacillus in the CM group decreased (P<0.05). Conclusion Intestinal dysbiosis in offspring due to chronic prenatal psychological stress, which may be one of the mechanisms linking maternal stress to immune imbalance and increased susceptibility to eczema in offspring.

Objective:To screen the main characteristic variables affecting the incidence of cardiovascular and cerebrovascular diseases,and to construct the Bayesian network model of cardiovascular and cerebrovascular disease incidence risk based on the top 10 characteristic variables,and to provide the reference for predicting the risk of cardiovascular and cerebrovascular disease incidence.Methods:From the UK Biobank Database,315 896 participants and related variables were included.The feature selection was performed by categorical boosting(CatBoost)algorithm,and the participants were randomly divided into training set and test set in the ratio of 7∶3.A Bayesian network model was constructed based on the max-min hill-climbing(MMHC)algorithm.Results:The prevalence of cardiovascular and cerebrovascular diseases in this study was 28.8％.The top 10 variables selected by the CatBoost algorithm were age,body mass index(BMI),low-density lipoprotein cholesterol(LDL-C),total cholesterol(TC),the triglyceride-glucose(TyG)index,family history,apolipoprotein A/B ratio,high-density lipoprotein cholesterol(HDL-C),smoking status,and gender.The area under the receiver operating characteristic(ROC)curve(AUC)for the CatBoost training set model was 0.770,and the model accuracy was 0.764;the AUC of validation set model was 0.759 and the model accuracy was 0.763.The clinical efficacy analysis results showed that the threshold range for the training set was 0.06-0.85 and the threshold range for the validation set was 0.09-0.81.The Bayesian network model analysis results indicated that age,gender,smoking status,family history,BMI,and apolipoprotein A/B ratio were directly related to the incidence of cardiovascular and cerebrovascular diseases and they were the significant risk factors.TyG index,HDL-C,LDL-C,and TC indirectly affect the risk of cardiovascular and cerebrovascular diseases through their impact on BMI and apolipoprotein A/B ratio.Conclusion:Controlling BMI,apolipoprotein A/B ratio,and smoking behavior can reduce the incidence risk of cardiovascular and cerebrovascular diseases.The Bayesian network model can be used to predict the risk of cardiovascular and cerebrovascular disease incidence.

Objective:To discuss the clinical characteristics of the patients with ovarian clear cell carcinoma(OCCC)and ovarian endometriosis(OMA),and to clarify the features of OCCC onset.Methods:A retrospective analysis was conducted on the clinical data of 80 patients with post-operative pathological diagnosis of OCCC and 80 OMA patients diagnosed by post-operative pathology,who received surgical treatment from March 2011 to May 2021.The analysis included general characteristics,clinical manifestations,laboratory indices,and imaging examination indexes.The age,body mass index(BMI),clinical symptoms such as abdominal pain,vaginal bleeding,and other symptoms(bloating,menstrual disorders,constipation,and abnormal vaginal discharge),preoperative serum carbohydrate antigen 125(CA125)levels,and ultrasound characteristics of ovarian cysts,such as cyst size,presence of pelvic effusion,and complexity,were compared between the patients in two groups.Multivariate Logistic regression analysis was used to identify the risk factors for OCCC,and the receiver operating characteristic(ROC)curve was drawn,and the area under the curve(AUC)was calculated.Results:Compared with OMA group,the age of the patients in OCCC group was significantly increased(P<0.05),the serum CA125 level was significantly increased(P<0.05),the diameter of ovarian cyst was significantly increased(P<0.05),and the percentage of the patients with pelvic effusion,other symptoms,and complex cysts was significantly increased(P<0.05).The multivariate Logistic regression analysis results showed that age≥40 years(OR=56.856,95%CI:5.611-576.082,P=0.001),complex ovarian cysts(OR=4.427,95%CI:1.025-19.114,P=0.046),concomitant pelvic effusion(OR=8.760,95%CI:1.574-48.760,P=0.013),and size of ovarian cysts(OR=1.782,95%CI:1.329-2.390,P<0.01)were the risk factors for OCCC.When the cut-off value of the ovarian cyst size was 7.35 cm,the sum of sensitivity(83.75%)and specificity(80.00%)was the highest,and the AUC was 0.883,indicating certain predictive value for identifying OCCC.Conclusion:The patients aged≥40 years with cysts≥7.35 cm in diameter,especially those with complex cysts accompanied by pelvic effusion,have a higher risk of malignancy to OCCC,and active intervention is recommended.

Objective:To discuss the clinical efficacy of recombinant human growth hormone(rhGH)in the treatment of the pediatric patients with growth hormone deficiency(GHD)and idiopathic short stature(ISS),and to clarify its clinical application value in the pediatric patients with short stature of different etiologies.Methods:The clinical data of 132 children with short stature who treated with rhGH from January 2018 to January 2023 were collected.They were divided into GHD group(n=70)and ISS group(n=62)based on different etiologies.The bone age,target height(TH),body mass index(BMI),height standard deviation score(HtSDS),changes in height standard deviation scores(ΔHtSDS)before treatment and 6 months after treatment,and growth velocity(GV)of the pediatric patients were calculated.Propensity score matching(PSM)and inverse probability of treatment weighting(IPTW)were used to balance the confounding factors between the pediatric patients in two groups and the efficacy and safety of the pediatric patients in two groups were evaluated.Results:There were significant differences in whether children were full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).Compared with before treatment,the height and HtSDS of the pediatric patients in both GHD and ISS groups were significantly increased after treated for 6 months(P<0.05).Before matched by PSM,there were significant differences in full-term,bone age,bone age maturity,and TH of the pediatric patients between two groups(P<0.05).After matched by PSM,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);the standardized mean difference(SMD)differences of covariates except for region were<0.2.After weighted by IPTW,there were no significant differences in gender,region,term birth status,mode of delivery,feeding method,age,bone age,height,BMI,TH,and pretreatment HtSDS of the pediatric patients between two groups(P>0.05);all SMD of covariates except for term birth status were<0.2.Before balancing covariates,after meatched by PSM matching,and after weighted by IPTW weighting compared with GHD group,the GV and ΔHtSDS of the pediatric patients in ISS group were slightly increased,but the difference was not significant(P>0.05).In terms of adverse reactions,2 cases(2.68%)of fasting hyperglycemia and 7 cases(10.00%)of hypothyroidism occurred in GHD group;3 cases(4.84%)of fasting hyperglycemia and 2 cases(3.23%)of hypothyroidism occurred in ISS group.Conclusion:rhGH can promote the height increase in the patients with GHD and ISS,and there is no significant difference in the height-increasing efficacy between GHD and ISS children.The incidence of adverse reactions is relatively low during treatment,indicating good overall safety.

Purpose/Significance By using data mining methods,the medication rules and prescription characteristics of traditional Chinese medicine(TCM)for treating hypertension with preserved ejection fraction heart failure are discussed.Method/Process The da-tabase is established based on the TCMprescription information of hypertensive patients with preserved ejection fraction heart failure ad-mitted to the Cardiovascular Disease Department of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine from Janu-ary 2019 to July 2022.SPSS Statistics and Moderler software are used to analyze the frequency,taste,meridian tropism,efficacy,associ-ation rules,clustering and factor analysis of the prescriptions to explore medication rules.Result/Conclusion TCMin the treatment of hy-pertension with preserved ejection fraction heart failure is mainly to replenish qi and spleen,nourish the heart and calm the mind,relieve phlegm,relieve cough and asthma,and pay attention to promoting blood circulation and removing blood stasis,promoting water infiltra-tion and dampness,which can reflect the overall concept of TCMand the characteristics of diagnosis and treatment based on syndrome dif-ferentiation and provide references for clinical medication.

AIM:To observe the anti-scarring effects and safety of triamcinolone acetonide(TA)-loaded hydrogel sustained-release sheeting on stab incision glaucoma surgery(SIGS)with “one-step tunnel method” in rabbit eyes.METHODS:A total of 48 healthy New Zealand white rabbits were randomly selected and divided into 4 groups(12 rabbits in each group), trabeculectomy(Trab)group, SIGS group, polyvinyl alcohol hydrogel(PVAH)sheeting was implanted under the conjunctiva flap during SIGS(PVAH group), and hydrogel sustained-release sheeting loaded with TA was implanted under the conjunctiva flap during SIGS(TA/PVAH group). On the 1, 2, 3, and 4 wk after surgery, the intraocular pressure, filtering bubble morphology, anterior chamber reaction, and other complications were observed and recorded in each group. Then animals were euthanized, and the surgery area tissues of right eye were taken for pathological tissue paraffin section. Masson staining, picric acid-Sirius rose red staining, as well as α-smooth muscle actin(α-SMA)and fibroblast growth factor 2(FGF2)immunohistochemistry staining was performed on every section. The infiltration of inflammatory cells, proliferation of fibroblasts and synthesis of type I and type III collagen fibers in local tissues were observed. The average positive area ratio of α-SMA and FGF2 antibody immunohistochemical staining in each group was calculated and compared.RESULTS: The TA/PVAH group maintained diffuse and elevated functional filtering blebs, while flat filtering blebs appeared in Trab, SIGS and PVAH groups at 2 wk after surgery. Functional filtering blebs were present in 1 eye(33%), 2 eyes(67%)in the PVAH and TA/PVAH group at 4 wk after surgery, respectively, while the other filtering blebs were flattened. Masson staining showed that the hydrogels in PVAH and TA/PVAH groups did not degrade at 4 wk after surgery. Compared with the Trab and SIGS groups, the filtration passages were more obvious, with less collagen fiber proliferation. Sirius red staining showed that the expression of type I collagen and type III collagen in the TA/PVAH group was less than that in the Trab group, SIGS group and PVAH group at 4 wk after surgery. Immunohistochemical staining showed that the α-SMA expression in the TA/PVAH group was significantly lower than that in the Trab and SIGS groups at 1 wk after surgery(P<0.01). The α-SMA expression was the highest in the Trab and SIGS groups at 2 wk after surgery, while the α-SMA expression in the PHAP and TA/PVAH groups was significantly lower than that in the first two groups(P<0.01). Compared with the Trab group, the expression of FGF2 in the PVAH and TA/PVAH group was significantly increased at 1, 2, 3 and 4 wk after surgery(P<0.05). Compared with the SIGS group, FGF2 expression in the TA/PVAH group was significantly increased at 4 wk after surgery(P<0.05).CONCLUSION:In SIGS surgery of rabbit eyes, implanting hydrogel sustained-release sheeting loaded with TA under conjunctival flap can effectively inhibit the scarring of the filtering bleb, which may be the interaction of the anti-scar effect of TA and the stent function of hydrogel.

ObjectiveTo predict the potential nephrotoxic components in traditional Chinese medicine health food products based on the Traditional Chinese Medicine Toxicity Alert System and Basic Toxicology Database （TCMTAS-BTD）， screen and validate the predicted components by cell and animal experiments， and decipher the mechanism of nephrotoxicity by network pharmacology. MethodTCMTAS-BTD was utilized to predict the toxicity of 3 540 compounds found in the catalogue of traditional Chinese health food ingredients. In the cell experiment， the top 5 compounds with high toxicity probability were screened by measurement of cell proliferation and viability （CCK-8） and high-content screening. ICR mice were randomized into a control group， a low-dose （2.91 mg·kg^-1·d^-1） ecliptasaponin A， and a high-dose （29.1 mg·kg^-1·d^-1） ecliptasaponin A group， with 10 mice in each group， and treated continuously for 28 days. During the experiment， the general conditions of the rats were observed， and the kidney index was calculated. The levels of serum creatinine （SCr） and blood urea nitrogen （BUN） in the serum as well as the content of malondialdehyde （MDA） and superoxide dismutase （SOD） in the renal tissue were measured. The pathological changes of the kidney were observed. Network pharmacology was employed to predict the potential pathways of nephrotoxicity. Finally， the pathway-associated proteins were validated by Western blot. ResultThe top 5 compounds with high probability of nephrotoxicity were ecliptasaponin A， chrysophanol， rutaecarpine， tanshinoneⅠ， and geniposidic acid. In the cell experiment， CCK-8 results showed that 10 μmol·L^-1 ecliptasaponin A， 60 μmol·L^-1 chrysophanol， 40 μmol·L^-1 rutaecarpine， and 20 μmol·L^-1 tanshinone I altered the viability of HK-2 cells. High-content analysis showed that 10 μmol·L^-1 ecliptasaponin A， chrysophanol， rutaecarpine， and tanshinone Ⅰ reduced the cell number （P<0.05， P<0.01）. The animal experiment showed that the mice in the high-dose ecliptasaponin A group presented slow movement， slow weight gain （P<0.01）， increased kidney index （P<0.01）， elevated SCr， BUN， and MDA levels （P<0.01）， and lowered SOD level （P<0.01）. Mild histopathological changes were observed in the high-dose ecliptasaponin A group. The network pharmacology results showed that the key targets of nephrotoxicity induced by ecliptasaponin A were mainly enriched in the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， prostatic cancer and lipid and atherosclerosis pathways. Western blot results verified that high dose of ecliptasaponin A raised the phosphorylation levels of PI3K and Akt （P<0.01）. ConclusionOn day 28 of administration， 29.1 mg·kg^-1 ecliptasaponin A was found to induce renal injury in rats. The mechanism may be related with the PI3K/Akt signaling pathway， which implied that excessive and prolonged usage of Ecliptae Herba may increase the incidence of adverse drug reactions.

Objective:To investigate the long-term therapeutic effects and safety of renal denervation (RDN) on hypertensive patients with different cardiovascular risks, as well as its impact on adverse events, cardiovascular death and all-cause mortality.Methods:This was a single-center, single-arm, real-world retrospective study. Patients with refractory hypertension who underwent RDN at Tianjin First Central Hospital from July 6, 2011 to December 23, 2015 were enrolled and divided into either a high or intermediate-low risk group based on baseline cardiovascular risk. The treatment responsiveness of hypertensive patients with different cardiovascular stratification to RDN was assessed by comparing the results of office blood pressure, home blood pressure, and 24-h ambulatory blood pressure monitoring at 1, 5, and 11 years after RDN. Long-term safety of RDN was assessed by creatinine, and estimated glomerular filtration rate (eGFR) at 1 and 11 years after RDN. In addition, the total defined daily dose (DDD) of antihypertensive medications and the incidence of long-term adverse events, cardiovascular deaths, and all-cause deaths after RDN were followed up 11 years after RDN in person or by telephone.Results:A total of 62 patients with refractory hypertension, aged (50.2±15.0) years, of whom 35 (56.5%) were male, were included. There were 35 cases in high-risk group and 27 cases in low and medium risk group. The decrease in clinic systolic blood pressure (high risk vs. low-medium risk: (-38.0±15.1) mmHg vs. (-25.0±16.6) mmHg(1 mmHg=0.133kPa), P=0.002), home self-measured systolic blood pressure ((-28.4±12.7) mmHg vs. (-19.7±13.1) mmHg, P=0.011) and clinic systolic blood pressure 11 years after RDN ((-43.0±18.4) mmHg vs. (-27.8±17.9) mmHg, P=0.003) in the high-risk group was significantly higher than that in the low-medium risk group. The differences in heart rate and the decrease in total DDD number of antihypertensive drugs between the two groups were not statistically significant (all P>0.05). Creatinine and eGFR levels in the two groups at 1 and 11 years after RDN were not statistically significant when compared with the baseline values (all P>0.05). The cumulative cardiovascular mortality rate was 1.6% (1/62) and 8.1% (5/62), and the cumulative all-cause mortality rate was 3.2% (2/62) and 11.3% (7/62) at 5 and 11 years after RDN, respectively. The differences in the incidence rate of adverse events, cardiovascular mortality, and all-cause mortality rate between the two groups were not statistically significant (all P>0.05). Conclusions:RDN has long-term antihypertensive effect and good safety. Hypertensive patients who belong to the high-risk stratification of cardiovascular risk may respond better to RDN treatment.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To explore the genetic etiology of pediatric intensive care unit (PICU) mortality cases and summarize their clinical characteristics.Methods:This was a retrospective cohort study. The study population consisted of 234 children who died within 7 d after admitted to the PICU of Children′s Hospital of Fudan University from January 2017 to December 2021. The clinical diagnoses, laboratory test results, and genetic testing results were collected. These patients were divided into the pathogenic gene variation positive (PGVP) group and the pathogenic gene variation negative (PGVN) group according to the results of genetic testing. The Mann-Whitney U test and Pearson′s chi-square test or Fisher′s exact probability method were used to compare the clinical characteristics between the groups. Results:A total of 234 cases were enrolled, including 139 (59.4%) males and 95 (40.6%) females. The age at death was 1.0 (0.4, 3.7) years old and the length of PICU stay was 16 (6, 33) days. There were 62 cases (26.5%) PGVP, and the mutated pathogenic genes included immune genes (23 cases (37.1%)), metabolic genes (11 cases (17.7%)), neuromuscular genes (11 cases (17.7%)), cardiovascular genes (4 cases (6.5%)), and genes of other systems (13 cases (21.0%)). The age at death in PGVP cases was significantly lower than in PGVN cases (0.6 (0.3, 1.4) vs. 1.3(0.5, 4.3) years old, Z=3.85, P<0.001). Compared with the PGVN group, the PGVP group had a higher incidence of family history and chronic complex conditions (CCC) than the PGVN group (6.5% (4/62) vs. 0.6% (1/172) and 93.5% (58/62) vs. 76.2% (131/172), χ2=8.87, P=0.018 and 0.003, respectively). Children in the PGVP group were admitted with higher incidence of severe infection, decreased consciousness or coma, moderate-to-severe anemia, thrombocytopenia, protracted diarrhea, and abnormalities in muscle strength or tone than those in the PGVN group (74.2%(46/62) vs. 45.9%(79/172), 50.0%(31/62) vs. 35.5%(61/172), 32.3%(20/62) vs. 18.0%(31/172), 21.0%(13/62) vs. 10.5%(18/172), 25.8%(16/62) vs. 4.1%(7/172), 16.1%(10/62) vs. 5.2%(9/172), χ2=14.63, 4.04, 5.41, 4.37, 24.30, 7.25, all P<0.05). Pathogenic genes that occurred more than twice included IL2RG (5 cases), SMN1 (4 cases), and SH2D1A (3 cases, including 2 single gene varients and 1 copy number varient). Conclusions:Among the deceased cases in the PICU, the main genetic causes are immune-related, metabolic, and neuromuscular genetic disorders. Critically ill children with a family history, CCC, and early features such as severe infections, decreased consciousness or coma, moderate to severe anemia, thrombocytopenia, protracted diarrhea, or abnormalities in muscle strength or tone should be closely monitored and undergo early genetic testing.