BACKGROUND:Croton cream can activate ERK pathways and have anti-apoptotic effects on neuronal cells.It is not clear whether it synergistically exerts anti-apoptotic effects by inhibiting the activation of JNK and p38 pathways. OBJECTIVE:To explore the effects and mechanisms of croton cream on neuronal damage and apoptosis in the ischemic cortex of rats with cerebral ischemia-reperfusion injury. METHODS:(1)Ninety Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream low-dose group,croton cream medium-dose group,croton cream high-dose group and nimodipine group,with 15 rats in each group.Except for the sham operation group,animal models of middle cerebral artery occlusion were prepared in rats by the thread method.Rats in the three croton cream groups were given 20,40,and 60 mg/kg croton cream,respectively.Rats in the sham operation and model groups were given the same amount of normal saline,once a day,for 7 consecutive days.The optimal concentration of croton cream,namely the high dose of croton cream,was selected based on neurological deficit score,TTC staining,brain tissue water content,hematoxylin-eosin staining and Nissl staining.(2)Another 120 Sprague-Dawley rats were randomly divided into sham operation group,model group,croton cream group,JNK inhibitor group,croton cream+JNK inhibitor group,p38 MAPK inhibitor group,croton cream+p38 MAPK inhibitor group,and nimodipine group,with 15 rats in each group.Animal models of middle cerebral artery occlusion were prepared using the thread method in all the groups except in the sham operation group.Thirty minutes before modeling,10 μL of SP600125(JNK inhibitor)and 10 μL of SB203580(p38 MAPK inhibitor)were injected into the lateral ventricle of the rats,respectively.Rats in croton cream groups were intragastrically given 60 mg/kg croton cream.Seven days later,the JNK/p38 MAPK signaling pathway,apoptosis-related proteins and cell apoptosis were detected by western blot,TUNEL staining and flow cytometry,respectively. RESULTS AND CONCLUSION:(1)Compared with the sham operation group,neurological deficit score,cerebral water content,cerebral infarction volume and apoptosis rate were significantly increased in the model group(P<0.05),where nerve cells showed scattered distribution.Compared with the model group,neurological deficit score,water content of brain tissue and cerebral infarction volume were significantly decreased in the croton cream medium-dose group,high-dose group and nimodipine group(P<0.05),and the pathological morphology of nerve cells was significantly improved.(2)Compared with the JNK inhibitor group,p-JNK/JNK,p-p38/p38 and Bax expressions in rat brain tissue and the apoptotic rate were significantly decreased in the croton cream+inhibitor groups(P<0.05),while the expression of and Bcl-2 was significantly increased(P<0.05).To conclude,croton cream may inhibit the activation of JNK/p38 MAPK signaling pathway and reduce neuronal apoptosis to achieve neuroprotective effects in rats with cerebral ischemia-reperfusion injury.

【Objective】 To investigate the anemia status of infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture, Gansu Province, and to comprehensively evaluate the differences in feeding behaviors between anaemic and normal children through the infant and child feeding index (ICFI) and feeding knowledge scores, so as to provide reference for the guidance of infants and young children feeding in ethnic minority areas and the promotion of children′s growth and development. 【Methods】 Taking infants and young children aged 6 - 24 months in Linxia Prefecture as the study subjects, a multi-stage random sampling method was used to select children who met the requirements from 5 townships and 5 villages in 7 counties in 2019 and 2020.Periphral blood samples were collected to test the level of hemoglobin, so as to determine the anemia status.Meanwhile, physical examination was performed and a questionnaire survey of guardians was conducted to analyze the association betweenanaemia and feeding patterns 【Results】 A total of 3 901 infants and children were included in this study, of whom 729 (18.70%) were anaemic, with a mean ICFI score of 12.56±2.70 and a mean feeding knowledge score of 1.97±1.01.There was no statistically significant association of low feeding knowledge score and low ICFI with anaemia after adjusting for confounders (P>0.05), Unqualified meat addition in ICFI was a risk factor for anaemia (OR=1.355, P=0.042), while non-bottle feeding in the past 24 hours (OR=0.762, P=0.021), and breastfeeding in the past 24 hours of infants and toddlers aged 12 - 24 months (OR=0.228, P=0.018) were protective factor for anemia in infants and toddlers aged 12 - 24 months. 【Conclusions】 The average prevalence of anemia in infants and toddlers aged 6 - 24 months in Linxia Hui Autonomous Prefecture of Gansu Province is high, but the level of infant feeding and the level of feeding knowledge of caregivers are low.Early adherence to breastfeeding, timely addition of supplementary food, and more comsumpution of meat for children are conducive to preventing anemia.

Objective:To analyze the current situation and influencing factors of family economic burden in children with congeni-tal heart disease,and provide reference basis for relevant departments.Methods:Conduct a questionnaire survey on the parents of children with congenital heart disease,and use a multiple linear regression model to analyze the factors affecting the economic bur-den of the disease.Results:The median total economic burden of families with congenital heart disease is 44 140 yuan,which is higher than the average level of per capita disposable income among residents of Xinjiang from 2020-2022.The median direct non-medical economic burden is 2 700 yuan,and the median indirect economic burden is 2 890 yuan.The length of hospital stay and monthly household income are important factors affecting the total economic burden.Conclusion:The total economic burden of families with congenital heart disease is higher than the per capita disposable income.The more complex the condition,the longer the days of hospitalization and the longer the time lost from work,resulting in a higher overall financial burden.

Objective:To evaluate the clinical efficacy and safety of stereotactic surgery in patients with refractory mental disorders.Methods:A retrospective analysis was performed; clinical data, postoperative complications and medication intake of 149 patients with refractory mental disorders accepted stereotactic surgery in Department of Neurosurgery, People's Hospital, Wuhan University from August 2019 to December 2023 were collected. Outcomes were assessed at 1, 6, 12, and 24 months after surgery by Clinical Global Impression-Global Improvement (CGI-GI). Before and 1, 6, and 12 months after surgery, severities were assessed by Clinical Global Impression-Severity of Illness (CGI-SI); cognition was assessed by Montreal Cognitive Assessment (MoCA); positive and negative symptoms were evaluated by Positive and Negative Symptom Scale (PANSS); psychotic symptoms were evaluated by Brief Psychiatric Rating Scale (BPRS) and Symptom Checklist 90 (SCL-90); obsessive-compulsive symptoms, depressive symptoms, anxiety symptoms and manic symptoms were assessed by Yale-Brown Obsessive-Compulsive Symptoms Scale (Y-BOCS), Beck Depression Inventory (BDI)-II, Beck Anxiety Inventory (BAI), and Young Mania Rating Scale (YMRS), respectively; social functioning and quality of survival were evaluated by Social Disability Screening Schedule (SDSS) and World Health Organization Quality of Life-Bref Form (WHOQOL-BREF).Results:(1) Increased sleep was noted in 47 patients and fatigue in 38 patients within 1 week after surgery. Behavioral laziness and emotional apathy were still presented at 1 month after surgery in 6 patients, and complications disappeared in the rest patients. Mildly reduced initiative was presented at 12 months after surgery in 5 patients. (2) CGI-GI indicated that 149 patients were followed up 1 month after surgery with an overall efficiency of 85.90%; 135 patients were followed up at 6 months after surgery with an overall efficiency of 83.21%, 106 patients were followed up at 12 months after surgery with an overall efficiency of 79.24%, and 63 patients were followed up at 24 months after surgery with an overall efficiency of 80.95%. (3) Compared with those before surgery, significantly lower BPRS scores, significantly lower PANSS positive, negative, and overall scores, statistically lower BAI, BDI-II, YMRS, and MOAS scores, significantly lower Y-BOCS obsessional thinking, compulsive behavior and total scores, significantly higher WHOQOL-BREF (physical and psychological domains) scores, and significantly lower SDSS and SCL-90 scores were noted in patients at 1, 6, and 12 months after surgery ( P<0.05). (4) At 12 months after surgery, withdrawal drug was noted in 13 patients, reduced drug in 38, same dose in 52, and increased drug in 2 patients. Conclusion:Stereotactic surgery can obviously improve obsession, anxiety, depression, mania and aggression, and modify social functioning and quality of survival in patients with refractory mental disorders, enjoying good safety.

Objective:To discuss the role of serum and glucocorticoid-induced protein kinase 3(SGK3)in the resumption of the first meiotic division in the oocytes of the mice,and to preliminarily clarify the regulatory mechanism of SGK3 in the early development of mammalian oocytes.Methods:The germinal vesicle(GV)stage mouse oocytes were obtained by superovulation techniques.The SGK3 mRNA,obtained from in vitro transcription of expression plasmids,was injected into the GV stage oocytes by microinjection techniques.The oocytes were divided into control group,Tris-EDTA buffer(TE)group,and SGK3 mRNA group.Western blotting method was used to detect the expression levels of SGK3 protein in the oocytes in various groups;the germinal vesicle breakdown(GVBD)rates of the oocytes in various groups were observed and calculated at 1,2,3,and 4 h after microinjection of SGK3 mRNA;the morphological appearance of the oocytes in various groups was observed by SGK3 antibody dilution inhibition experiment;Western blotting method was used to detect the expression levels of phosphorylated SGK3(pSer48)(SGK3-pSer48)and phosphorylated cell division cycle protein 2(CDC2)(pTyr15)(CDC2-pTyr15)proteins in the oocytes cultured in vitro at different time points.Results:Compared with control group and TE group,the expression level of SGK3 protein in the oocytes in SGK3 mRNA group was increased(P＜0.01),and the GVBD rates at 1 and 2 h after microinjection were increased(P＜0.01).The SGK3 antibody dilution inhibition experiment results showed that as the increasing of concentration of SGK3 antibody,the GVBD rates of the oocytes in various groups were decreased in a concentration-dependent manner.After overexpressing SGK3,compared with control group,the time when CDC2-pTyr15 protein expression could not be detected in the oocytes in SGK3 mRNA group was advanced by at least 1 h.After treated with different concentrations of SGK3 antibody,compared with control group,as the increasing of concentration of SGK3 antibody and the extending of treatment time,the expression level of CDC2-pTyr15 protein in the oocytes was gradually decreased(P＜0.01),and the expression level of SGK3-pSer486 protein was gradually increased(P＜0.01).Conclusion:Over-expression of SGK3 can increase the GVBD rate of oocytes of the mice and accelerate the dephosphorylation of CDC2-pTyr15,while the dephosphorylation of CDC2-pTyr15 is later than the phosphorylation of SGK3-Ser486.SGK3 likely serves as an upstream regulator of CDC2 and participates in controlling the resumption of the first meiotic division in the oocytes of the mice.

OBJECTIVE To observe the effect of Huangjing Jiangya Decoction on blood pressure and sleep in patients with hy-pertension of qi-deficiency type accompanied by insomnia.METHODS 73 patients with hypertension of qi-deficiency type accompa-nied by insomnia who met the inclusion criteria were selected and randomly divided into an observation group of 36 cases and a control group of 37 cases.The control group was treated with amlodipine besylate tablets,and the observation group was given Huangjing Jian-gya Decoction oral treatment on the basis of the control group.Both groups were treated continuously for 8 weeks.The changes in TCM syndrome scores,office blood pressure monitoring(OBPM),home blood pressure monitoring(HBPM),24-hour ambulatory blood pressure monitoring(ABPM),Pittsburgh Sleep Quality Index(PSQI)scores and clinical efficacy of the two groups of patients before and after treatment were observed.RESULTS After treatment,the TCM syndrome scores in the observation group were significantly decreased(P<0.05,P<0.01),which were better than the control group(P<0.01);OBPM and HBMP in both groups were signifi-cantly reduced(P<0.05,P<0.01),the observation group was better than the control group(P<0.05,P<0.01);the ABPM of the observation group was significantly reduced(P<0.01),which was better than the control group(P<0.05,P<0.01);the sleep quali-ty,sleep latency,sleep duration,daytime dysfunction score and PSQI total score of the observation group were significantly decreased(P<0.01),which were better than those in the control group(P<0.05,P<0.01);the clinical efficacy of hypertension and insomnia in the observation group was both better than the control group(P<0.01).CONCLUSION Huangjing Jiangya Decoction combined with amlodipine can improve the symptoms of patients with hypertension of qi-deficiency type accompanied by insomnia,lower blood pressure,improve sleep quality,shorten sleep latency,alleviate daytime dysfunction,and has good clinical efficacy.

Objective:To study the distribution of drug resistance genes and virulence genes in multidrug-resistant Salmonella typhimurium strains.Methods:A total of 96 strains of Salmonella typhimurium were collected，and drug sensitivity tests were performed to evaluate the drug resistance and multidrug-resistance of Salmonella typhimurium.Multidrug-resistant Salmonella typhimurium strains were selected to conducted whole genome sequencing，and the distribution of drug resistance genes and virulence genes in the strain were analyzed.Results:Salmonella typhimurium strains had the highest resistance rates to ampicillin and ampicillin/sulbactam，with 89.58% and 76.04%，respectively.Followed by trimethoprim/sulfamethoxazole，ceftriaxone，and aztreonam，with 47.92%，38.54% and 33.33%，respectively，and low resistance rates to ciprofloxacin and levofloxacin，with 8.33% and 4.17%，respectively.Ninety-six strains were all sensitive to carbapenem antibiotics and piperacillin/tazobactam.Fifty-seven strains（59.38%）of Salmonella typhimurium showed multidrug-resistance.Resistance genes were detected in all 57 multidrug-resistant Salmonella typhimurium strains,with higher carrier rates of 98.25%,77.19%,and 59.65% for aac(6')-Iaa,aadA22,and blaTEM-1B,respectively.The multidrug-resistant Salmonella typhimurium strains had the highest carrier rates for invA，sipA，sseL，and sopB.Conclusion:Multidrug-resistant Salmonella typhimurium strains have a high incidence and a high carrier rate for multiple drug resistance genes and virulence genes.The monitoring and prevention of Salmonella typhimurium should be strengthened in the clinic in order to reduce the spreading epidemic of multidrug-resistant strains.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

Objective:To investigate the clinicopathologic characteristics, gene mutation profile and prognostic influencing factors of diffuse large B-cell lymphoma (DLBCL) complicated with follicular lymphoma (FL) (DLBCL/FL).Methods:The clinicopathological data of 50 DLBCL/FL patients admitted to Rui Jin Hospital Affiliated of Shanghai Jiao Tong University School of Medicine from February 2018 to November 2021 were retrospectively analyzed. Targeted sequencing was performed to assess the mutation profile of 55 lymphoma-related genes. The clinicopathological characteristics were summarized to evaluate the short-term therapeutic efficacy of all patients. Kaplan-Meier method was used to analyze the overall survival (OS) and progression-free survival (PFS) of patients. Cox regression risk models were used to assess the factors affecting the OS and PFS.Results:Among 50 DLBCL/FL patients, 23 cases (46%) were male, 22 cases (44%) had an international prognosis index (IPI) score ≥ 2 points, 16 cases (32%) were double-expression lymphoma (DEL) and 4 cases (8%) were double-hit lymphoma (DHL). The complete response (CR) and overall response rates were 68% (34/50) and 78% (39/50), respectively after the first-line therapy. The median follow-up time was 23.3 months (5.1-50.9 months). The 2-year OS rate was 82.1% and 2-year PFS rate was 67.1%; and the median OS and PFS were not reached. Targeted sequencing results showed that the mutation frequencies of KMT2D, MYD88, TP53, BTG2, DTX1, EZH2, CD70, CREBBP, DUSP2, HIST1H1C, HIST1H1E and PRDM1 genes in this cohort were more than 15%. Multivariate Cox regression analysis showed that male ( HR = 4.264, 95% CI 1.144-15.896, P = 0.031) and IPI score ≥ 2 points ( HR = 6.800, 95% CI 1.771-37.741, P = 0.007) were independent risk factors of PFS in newly diagnosed DLBCL/FL patients, and TP53 mutation ( HR = 4.992, 95% CI 1.027-24.258, P = 0.046) was an risk influencing factor of OS. Conclusions:The proportion of male and female DLBCL/FL patients is similar, with a small proportion of DHL. Mutations of KMT2D, MYD88 and TP53 genes are commonly found in DLBCL/FL patients. Generally, DLBCL/FL patients can have a high overall response and good prognosis. Male and IPI score ≥ 2 points are the independent risk factors of PFS, and TP53 mutation is an independent risk factor of OS in DLBCL/FL patients.

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.