OBJECTIVE To investigate the ameliorative effect and potential mechanism of imperatorin （IMP） on doxorubicin （DOX） resistance in breast cancer. METHODS The effects of maximum non-toxic concentration （100 μg/mL） of IMP combined with different concentrations of DOX （12.5， 25， 50， 75， 100 μg/mL） on the proliferation of MCF-7/DOX cells were determined by MTT method. MCF-7/DOX cells were divided into blank control group （1‰ dimethyl sulfoxide）， DOX group （50 μg/mL）， IMP+DOX group （100 μg/mL IMP+50 μg/mL DOX） and IMP group （100 μg/mL）. mRNA and protein expressions of multidrug resistance protein 1 （MDR1） and multidrug resistance-associated protein 1 in each group were measured. The relevant pathways and targets involved in the improvement of DOX resistance in breast cancer cells by IMP were screened and validated by using transcriptome sequencing technology， along with gene ontology （GO） enrichment analyses and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses. RESULTS Compared with DOX alone， the combination of IMP and DOX reduced the half inhibitory concentration of DOX on MCF-7/DOX cells from 81.965 μg/mL to 43.170 μg/mL， the reverse fold was 1.90， and the mRNA expression of MDR1 was significantly down-regulated （P＜0.05）. The results of GO enrichment analyses and KEGG pathway enrichment analyses indicated that the reversal of DOX resistance in breast cancer by IMP was mainly associated with the regulation of biological processes such as detoxification， multiple biological processes， and cell killing. The main pathway involved was the p53 signaling pathway， and the key targets mainly included constitutively photomorphogenic protein 1 （COP1）， cyclin E1 （CCNE1）， growth arrest and DNA damage-inducible protein 45A E-mail：tangxilan1983@163.com （GADD45A） and GADD45B. The results of the verification experiments showed that compared with DOX group， there was a trend of up-regulation of COP1 mRNA， and significant down- regulation of CCNE1， GADD45A， and GADD45B mRNA expression in IMP+DOX group （P＜0.05）. CONCLUSIONS The effect of IMP in ameliorating DOX resistance in breast cancer is related to its regulation of COP1， CCNE1， GADD45A and GADD45B targets in the p53 signaling pathway.

The discussion on the connotation of children’s subjectivity is not only a response to the lack of children’s subjectivity at the current stage of health management, but also a reference for children’s medical science popularization. Based on the perspective of social critical theory, this study used empirical research methods to review the "Dream Medical College" project of Children’s Hospital of Fudan University. The current situation and influencing factors of health management experience of 1 520 children participating in the "Dream Medical College" project were analyzed. The study showed that 96.35% of 1 316 subjects had diagnosis and treatment experience in specialized hospitals, and the overall negative emotional performance was at a low level (0~12 points). There was significant correlation between diagnosis and treatment, invasive experience and children’s emotional performance (P<0.05). The study revealed that the diagnosis and treatment field is the main practice place of children’s health management, while the subjective of children with different diagnosis and experience perform significantly different. Children over 4 years old have better language anxiety than physical anxiety when receiving diagnosis and treatment. Although medical science popularization is an important practical form of children’s health management, it lacks the science popularization content of invasive diagnosis and treatment and emotional management, and creative popular science form is more suitable for children with long-term and frequent diagnosis and treatment experience.

Objective To investigate the effect of mogrol on lung injury in rats with severe acute pancreatitis and its possible mechanism.Methods The model of lung injury in rats with severe acute pancreatitis was established by retrograde injection of 4%sodium taurocholate into the biliopancreatic duct,After modeling,they were divided into model group,mogrol low,medium and high dose groups(15,30,60 mg·kg-1),set up another sham operation group,each group containing 12 rats.Intraperitoneal injection,one day once time,a total of 2 times.The pathological changes of pancreas and lung tissues were detected by HE staining;Serum amylase(AMS)and lipase(LPS)levels were detected by biochemical method;The levels of inflammatory cytokines interleukin-1β(IL-1β),interleukin-18(IL-18)and tumor necrosis factor-α(TNF-α)in rat alveolar lavage fluid were determined by ELISA;The activity of Caspase-1 in lung tissue of rats was detected by colorimetry;The expression levels of triggering receptor 1(TREM-1)and pyroptosis related proteins NLRP3,Caspasse-1,Gasdermin D(GSDMD)in lung tissue of rats were detected by Western blot.Results Compared with the sham operation group,the model group showed obvious pathological damage in pancreas and lung tissue.Serum AMS and LPS levels,inflammatory factors IL-1β,IL-18 and TNF-α levels,Caspase-1 activity,and protein expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD,in lung tissue were significantly increased(P<0.05);Compared with the model group,different doses of mogrol could improve the pathological damage of pancreas and lung tissue in rats,and significantly reduce the levels of serum AMS,LPS,inflammatory factors IL-1β,IL-18 and TNF-α,Caspase-1 activity and the expression levels of TREM-1 and NLRP3,Caspasse-1,GSDMD in lung tissue.Conclusion Mogrol may improve lung injury in rats with severe acute pancreatitis by inhibiting pyroptosis,and its mechanism may be related to the regulation of TREM-1/NLRP3 signaling pathway.

Snakebite is a common clinical emergency with the characteristics of acute onset,rapid changes in condition,and high disability and mortality rates.In addition to the common systemic and local tissue damage,snake envenomation can cause significant complications,including immediate and delayed effects.These complications are the main causes of disability and even death caused by snakebites,which seriously affect the long-term prognosis and quality of life.This article summarizes the symptoms,diagnosis,and treatment of snakebite complications from the aspects of blood,nervous,motor,endocrine,and reproductive systems and other aspects to provide references for effective and precise treatment of snakebite in clinical practice.

Objective To study the effect of Ditan Decoction combined with aripiprazole and olanzapine in the treatment of schizophrenia and its influence on serum inflammatory factors chnage.Methods Seventy-seven patients with schizophrenia meeting the requirements visiting the outpatient department and hospitalized in Dazu District Hospital of Traditional Chinese Medicine and Dazu District Mental Health Center from July 2021 to March 2023 were selected as the study subjects and divided into the observation group(n=38)and control group(n=39).The control group was treated with aripiprazole and olanzapine,and the observation group was combined with Ditan Decoction on the basis of the control group.After 8 weeks of treatment,the TCM syndrome scores,Positive and Negative Syndrome Scale(PANSS)score,serum inflammatory factors(IL-6,IL-1β,IL-17)levels were compared between the two groups.Results The total effective rate was 97.37％in the observation group and 84.65％in the control group,and the difference was statistically signifi-cant(P＜0.05).The TCM syndrome score of each item and total scores after treatment in the observation group were lower than those in the control group(P＜0.05),the PANSS positive symptoms,negative symp-toms,general psychopathology and total scores in the observation group were lower than those in the control group(P＜0.05).The IL-17,IL-6 and IL-1β levels after treatment in observation group were lower than those in the control group(P＜0.05).Conclusion Ditan Decoction combined with aripiprazole and olanzapine has significant clinical efficacy in the treatment of schizophrenia,which could further reduce the symptom score of the patients and improve the serum inflammatory factors levels.The treatment is highly safe and worthy of clinical recommendation.

Snake bites are characterized by acute onset,rapid changes in condition,and high disability and mortality rates.The effects of snake venom on the human body are divided into systemic and local toxic effects.The popu-larity of antivenom has greatly reduced the mortality of snake bites,but local tissue damage and permanent dysfunction are still problems to be solved urgently.Studies have found that snake venom metalloproteinases,hyaluronidases,phospholi-pases and other venoms participate in a variety of local pathological effects by interfering with the degradation and remodel-ing of extracellular matrix(ECM).This article reviews the mechanism of ECM in the development of local tissue damage caused by snake bites,in order to find effective therapeutic targets and provide reference and ideas for the clinical research and prevention of local tissue damage caused by snake bites.

Objective:To investigate the efficacy and safety of immune checkpoint inhibitors (ICI), programmed death receptor 1 (PD-1) inhibitors and programmed death receptor-ligand 1 (PD-L1) inhibitors in the treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:The databases of CNKI, Wanfang, VIP, China Biology Medicine disc, PubMed, Embase, and Cochrane Clinical Controlled Trial Center Registry (CENTRAL) were retrieved, and the randomized controlled trial literature on the treatment of ES-SCLC with immune checkpoint inhibitors published from the establishment of the database until October 4, 2023 were reviewed. After screening literature and extracting data according to inclusion and exclusion criteria, the risk of bias in the study was evaluated using Review Manager 5.4 software. The disease remission, prognosis and adverse events (AE) of patients treated with ICI combined with chemotherapy (experimental group) and placebo± chemotherapy (control group) in the whole group and liver metastases and brain metastases subgroups were compared.Results:A total of 11 randomized controlled trials were included, with 2 243 cases in the experimental group and 2 059 cases in the control group. The included research data were complete and showed no selective bias. Compared with the control group, the objective response rate (ORR) of patients in the experimental group was higher [control group vs. experimental group, 64% (864/1 358) vs. 70% (1 088/1 532), RR = 1.08 (95% CI: 1.03-1.14), P = 0.003], and the difference was statistically significant; progression free survival (PFS) [experimental group vs. control group, the median PFS time, 5.14 months (95% CI: 4.88-5.40 months) vs. 4.76 months (95% CI: 4.70-4.82 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] and overall survival (OS) [experimental group vs. control group, the median OS time, 12.89 months (95% CI: 12.18-13.60 months) vs. 10.41 months (95% CI: 10.03-10.79 months), HR = 0.72 (95% CI: 0.67-0.78), P < 0.001] were all improved, and the differences were statistically significant. The OS of patients with baseline liver metastasis in the experimental group was better than that in the control group (experimental group vs. control group, HR = 0.82 (95% CI: 0.71-0.95), P = 0.009], and the difference was statistically significant, while the difference in OS of patients with baseline brain metastases was not statistically significant between the experimental group and the control group [experimental group vs. control group, HR = 0.84 (95% CI: 0.66-1.08), P = 0.170]. The incidence of AE [experimental group vs. control group, 31% (597/1 952) (95% CI: 24%-37%) vs. 14% (255/1 762) (95% CI: 9%-22%), RR = 2.25 (95% CI: 1.67-3.02), P < 0.001] and the incidence of drug discontinuation or dose change caused by AE [experimental group vs. control group, 21% (379/1 774) (95% CI: 12%-41%) vs. 19% (307/1 588) (95% CI: 6%-25%), RR = 1.20 (95% CI: 1.07-1.33), P = 0.001] in the experimental group were higher than those in the control group, and the differences were statistically significant. However, the incidence of severe (≥grade 3) AE in both the experimental group and the control group was 34% (620/1 814, 557/1 632) (both 95% CI: 32%-36%), and the difference was not statistically significant [experimental group vs. control group, RR = 1.00 (95% CI: 0.91-1.10), P = 0.960]. The incidence of hypothyroidism [experimental group vs. control group, 11% (118/1 083) (95% CI: 9%-13%) vs. 1% (11/886) (95% CI: 0-2%), RR = 8.56 (95% CI: 4.63-15.80), P < 0.001] and the incidence of hyperthyroidism [experimental group vs. control group, 7% (75/1 083) (95% CI: 5%-8%) vs. 2% (17/886) (95% CI: 1%-4%), RR = 3.27 (95% CI: 1.95-5.46), P < 0.001] in the experimental group were both higher than those in the control group, and the differences were statistically significant. Conclusions:ICI combined with chemotherapy can effectively improve the OS, PFS and disease remission of patients with ES-SCLC, as well as improve the survival of patients with liver metastases. However, there is no benefit in the survival of patients with brain metastases. The incidence of immune-mediated AE to ICI combined with chemotherapy has increased, but the overall safety is good.

BACKGROUND: Currently, the effect of the 2022 nationwide coronavirus disease 2019 (COVID-19) wave on the perioperative prognosis of surgical patients in China is unclear. Thus, we aimed to explore its influence on postoperative morbidity and mortality in surgical patients. METHODS: An ambispective cohort study was conducted at Xijing Hospital, China. We collected 10-day time-series data from December 29 until January 7 for the 2018-2022 period. The primary outcome was major postoperative complications (Clavien-Dindo class III-V). The association between COVID-19 exposure and postoperative prognosis was explored by comparing consecutive 5-year data at the population level and by comparing patients with and without COVID-19 exposure at the patient level. RESULTS: The entire cohort consisted of 3350 patients (age: 48.5 ± 19.2 years), including 1759 females (52.5%). Overall, 961 (28.7%) underwent emergency surgery, and 553 (16.5%) had COVID-19 exposure (from the 2022 cohort). At the population level, major postoperative complications occurred in 5.9% (42/707), 5.7% (53/935), 5.1% (46/901), 9.4% (11/117), and 22.0% (152/690) patients in the 2018-2022 cohorts, respectively. After adjusting for potential confounding factors, the 2022 cohort (80% patients with COVID-19 history) had a significantly higher postoperative major complication risk than did the 2018 cohort (adjusted risk difference [aRD], 14.9% (95% confidence interval [CI], 11.5-18.4%); adjusted odds ratio [aOR], 8.19 (95% CI, 5.24-12.81)). At the patient level, the incidence of major postoperative complications was significantly greater in patients with (24.6%, 136/553) than that in patients without COVID-19 history (6.0% [168/2797]; aRD, 17.8% [95% CI, 13.6-22.1%]; aOR, 7.89 [95% CI, 5.76-10.83]). Secondary outcomes of postoperative pulmonary complications were consistent with primary findings. These findings were verified through sensitivity analyses using time-series data projections and propensity score matching. CONCLUSION: Based on a single-center observation, patients with recent COVID-19 exposure were likely to have a high incidence of major postoperative complications. REGISTRATION NCT05677815 at https://clinicaltrials.gov/ .
Female ; Humans ; Adult ; Middle Aged ; Aged ; Cohort Studies ; COVID-19/complications* ; Pandemics ; Retrospective Studies ; Postoperative Complications/epidemiology*

This study aimed to observe the protective effect of momordicine I, a triterpenoid compound extracted from momordica charantia L., on isoproterenol (ISO)-induced hypertrophy in rat H9c2 cardiomyocytes and investigate its potential mechanism. Treatment with 10 μM ISO induced cardiomyocyte hypertrophy as evidenced by increased cell surface area and protein content as well as pronounced upregulation of fetal genes including atrial natriuretic peptide, β-myosin heavy chain, and α-skeletal actin; however, those responses were markedly attenuated by treatment with 12.5 μg/ml momordicine I. Transcriptome experiment results showed that there were 381 and 447 differentially expressed genes expressed in comparisons of model/control and momordicine I intervention/model, respectively. GO enrichment analysis suggested that the anti-cardiomyocyte hypertrophic effect of momordicine I may be mainly associated with the regulation of metabolic processes. Based on our transcriptome experiment results as well as literature reports, we selected glycerophospholipid metabolizing enzymes group VI phospholipase A 2 (PLA2G6) and diacylglycerol kinase ζ (DGK-ζ) as targets to further explore the potential mechanism through which momordicine I inhibited ISO-induced cardiomyocyte hypertrophy.Our results demonstrated that momordicine I inhibited ISO-induced upregulations of mRNA levels and protein expressions of PLA2G6 and DGK-ζ. Collectively, momordicine I alleviated ISO-induced cardiomyocyte hypertrophy, which may be related to its inhibition of the expression of glycerophospholipid metabolizing enzymes PLA2G6 and DGK-ζ.

We reported the clinical data of a neonate admitted to the Second Affiliated Hospital (Yuying Children's Hospital) of Wenzhou Medical University in November 2021 with autosomal recessive complete signal transducer and activator of transcription 1 ( STAT1) deficiency identified by whole exome sequencing. The baby boy received bacillus of calmette-guerin (BCG) vaccine 2 d after birth and presented with persistent high fever, increased white blood cell count and increased level of C-reactive protein (CRP) on 21 d after birth. Human cytomegalovirus (HCMV) was detected in both blood and bone marrow specimens. The patient improved after comprehensive treatment with antiviral agents, antibiotics and intravenous gammaglobulin. Oral anti-viral drugs were prescribed on discharge. However, the baby was rehospitalized due to a fever at 55 days. HCMV and Mycobacterium tuberculosis complex were detected in blood samples. The infant was transferred to the Children's Hospital of Fudan University due to persistent high fever even after active management and died after treatment withdrawal at 69 d after birth because of worsening infections and multiple organ failure. A homozygous mutation in the STAT1 gene was detected [c.1011_1012del, NM_007315: exon11: c.1011_1012del (p.V339Pfs*18)] and the child was diagnosed as autosomal recessive complete STAT1 deficiency. We concluded that the clinical manifestations of autosomal recessive complete STAT1 deficiency are bacterial infections caused by lethal low-pathogenic mycobacteria and life-threatening virus infections. Whole exome sequencing is of great value for early diagnosis and timely treatment. The prognosis of this disease is very poor, but the condition of the patients might be improved in a short period with early anti-tuberculosis and anti-viral treatment.