OBJECTIVE: To study the effects and mechanisms of juglone on the proliferation and apoptosis of acute myeloid leukemia (AML) cells. METHODS: Juglone and AML targets were collected from public databases, and the intersecting target clusters were taken for functional enrichment analysis to explore the potential mechanism of juglone in the treatment of AML. Then wet experiments were performed to verify. AML cell lines including KG-1a, MV-411, THP-1 and MOLM-13 were treated with different concentrations of juglone for 24 h. MTT assay was used to detect cell viability and determine the IC₅₀, and the most sensitive cell line was screened for subsequent experiments. Flow cytometry was used to detect the apoptosis of cells treated with different concentrations of juglone. Western blot was performed to check the expression of relevant proteins. RESULTS: Eleven targets were obtained as potential targets for juglone in the treatment of AML, and the top ten significantly enriched pathways were intrinsic pathway of apoptosis, programmed cell death, cytochrome c-mediated apoptotic response, apoptosis, apoptotic factor-mediated response, regulated necrosis, cytokine signaling in immune system, signaling by interleukins, oncogene induced senescence, and signal transduction. The cell viability of KG-1a, MV-411, THP-1 and MOLM-13 was decreased with increasing juglone concentration after 24 h of juglone treatment (r =-0.992, -0.886, -0.956, -0.910). Among them, MOLM-13 was the most sensitive to juglone. The results of flow cytometry showed that the apoptosis rate of MOLM-13 tended to significantly increase with the increasing concentration of juglone (r =0.99). At the same time point, p-RIPK1/RIPK1, p-RIPK3/RIPK3, and p-MLKL/MLK were decreased in each juglone concentration group compared with control group. CONCLUSION Juglone inhibits the viability of KG-1a, MV-411, THP-1 and MOLM-13 cells, and induces apoptosis of MOLM-13 cells, the mechanism of which may be related to the inhibition of RIPK1/RIPK3/MLKL signaling pathway.
Humans ; Naphthoquinones/pharmacology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Leukemia, Myeloid, Acute/pathology* ; Cell Line, Tumor ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism* ; Protein Kinases/metabolism* ; Signal Transduction ; Cell Survival/drug effects*

OBJECTIVE: To construct an integrated management model for early screening and diagnosis of PCa based on the Innovative Care for Chronic Conditions Framework (ICCC) and the 1+1 contract-based tiered diagnosis and treatment system (TDTS) in China. METHODS: Based on the 1+1 contract-based TDTS platform, we conducted PCa screening for the male residents aged 60 years and above during health check-ups in Pujin Community Health Center from January 1, 2023 to December 31, 2023. For those with abnormal total prostate-specific antigen (tPSA) ≥ 4 μg/L, we promptly referred them to higher-level hospitals for further diagnosis and treatment via the two-way referral green channel platform and information sharing service using the 1+1 contract model. We further analyzed the relevant data on screening and diagnosis. RESULTS: A total of 4 080 males aged 71.39±5.059 years received PCa screening from January to December 2023. PSA screening was performed in 43.96% of the male residents, revealing 654 cases of PSA abnormality, with a PSA positivity rate of 16.03%, which was higher than that found in the previous large-scale PCa screenings in other regions of China. Among the males with PSA abnormality, 292 (44.65%) expressed their willingness for medical referral, while the others did not seek further medical attention for reasons of being asymptomatic, low awareness of the disease, no accompany for medical visits, and concerns about further costs of diagnosis and treatment. Prostate biopsy was recommended to 154 cases after further examinations, which was accepted by 92 (59.74%). Fifty-eight cases were diagnosed with Pa, and thedetection rate reached 63.04%. CONCLUSION The integrated management model for PSA examination-based early screening and diagnosis of PCa using the 1+1 contract-based TDTS platform is plays a significant role in enhancing people's awareness and knowledge of PCa and improving the early detection rate of the malignancy.
Humans ; Male ; Prostatic Neoplasms/diagnosis* ; Early Detection of Cancer ; Prostate-Specific Antigen/blood* ; Aged ; China ; Mass Screening ; Middle Aged ; Chronic Disease

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Objective To explore whether ferulic acid can inhibit the progression of T-cell acute lymphoblastic leukemia in vivo and in vitro by regulating PTEN/PI3K/AKT signaling pathway.Methods The T-cell acute lymphoblastic leukemia Jurkat cells were divided into the control group,the ferulic acid treatment group and the LY294002 treatment group for in vitro experiment.The cells in the control group were given normal culture;cells in the ferulic acid treatment group were given different concentrations(1.25,2.5,5,10,20,40,80,160 μmol/L)of ferulic acid,respectively,and the cell proliferation was detected by CCK-8 method,to screen the experimental concentration;cells in the LY294002 treatment group were given 50 μmol/L PI3K/AKT inhibitor LY294002.The cells proliferation,apoptosis and invasion were detected by clone formation assay,flow cytometry and Transwell assay.The relative expression levels of nuclear protein Ki67,proliferating cell nuclear antigen(PCNA),cleaved caspase-3,cleaved caspase-9,E-cadherin,N-cadherin,Vimentin,PTEN,p-PI3K,PI3K,p-AKT and AKT proteins were detected by Western blot.The nude mice models of transplanted tumors were constructed by 30 male BALB/c nude mice,and they were averagely divided into the normal group and the ferulic acid treatment group for in vivo experiment.The normal group was given normal saline by gavage,while the ferulic acid treatment group was given 75 mg/kg ferulic acid by gavage after inoculating Jurkat cells.The weight and volume changes of transplanted tumors were compared,and the levels of Ki67,cleaved caspase-3/caspase-3,E-cadherin,N-cadherin,PTEN,p-PI3K,PI3K,p-AKT and AKT in tumor tissues were detected.Results In vitro experiment,compared with the control group,the clone formation rate of cells,number of invasion cells,Ki67,PCNA,N-cadherin,Vimentin,p-PI3K/PI3K and p-AKT/AKT in the 5,10,20 μmol/L ferulic acid treatment group and the LY294002 treatment group were significantly decreased(P<0.05),while the apoptosis rate,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,E-cadherin and PTEN were significantly increased(P<0.05).In vivo experiment,compared with the normal group,the weight and volume of tumors were reduced in the ferulic acid treatment group,Ki67,N-cadherin,p-PI3K/PI3K and p-AKT/AKT in tumor tissues were significantly decreased,cleaved caspase-3/caspase-3,E-cadherin and PTEN were significantly increased,with statistically significant differences(P<0.05).Conclusion Ferulic acid can inhibit the proliferation and invasion of T-cell acute lymphoblastic leukemia Jurkat cells in vivo and in vitro,and induce apoptosis,its mechanism may be related to the regulation of PTEN/PI3K/AKT signaling pathway.

Objective To analyze the therapeutic effect of anti-programmed death receptor 1(PD-1)/pro-grammed death ligand 1(PD-L1)and the characteristics of intestinal flora in patients with non-small cell lung cancer(NSCLC).Methods A total of 81 NSCLC patients admitted to the People's Hospital of Xinjiang Uygur Autonomous Region from January 2020 to January 2022 were taken as the research object.According to the patients'immunotherapy response,the patients were divided into non-response group and response group.The differences in clinical data and intestinal flora distribution between the two groups were compared,and the correlation between PFS and intestinal flora a diversity index was analyzed by Spearman correlation.Results The proportion of smoking patients in response group was significantly lower than that in non-re-sponse group,and the difference was statistically significant(x2=4.648,P=0.031).Chao1 index,ACE index and shannon wiener index patients in non-response group were lower than those in response group,while Simpson diversity index was higher than that in response group,with statistical significance(P＜0.05).Chao1 index,ACE index and shannon wiener index were positively correlated with PFS(r=0.526,0.579 and 0.539,all P＜0.05),while Simpson diversity index was negatively correlated with PFS(r=-0.867,P＜0.001).The principal coordinate analysis was used to analyze the β diversity structure of intestinal flora.The first principal component contribution rate was 70.36％,and the second principal component contribution rate was 16.63％.Conclusion The diversity and distribution of intestinal flora in NSCLC patients are related to anti-PD-1/PD-L1 therapy.The higher the diversity of intestinal flora,the more sensitive the anti-PD-1/PD-L1 therapy.

Abstract：Objective To improve the replication level of varicella⁃zoster virus（VZV）in human diploid cell line MRC⁃5 and increase the yield of VZV vaccine by reducing the expression of interferon（IFN）related genes via optimizing the cell line MRC⁃5. Methods Interferon receptor 1（IFNAR1）silenced MRC⁃5 cell line（MRC⁃5IFNAR1⁃）was constructed by CRISPR／Cas9 gene editing technology，which was determined for the relative expression of IFNAR1 mRNA，and for those of mRNA of IFN related genes IFNβ and OAS1 after VZV infection by qRT⁃PCR to evaluate the effect of gene silencing. Gene mutation sequences were further identified by sequencing of the silenced sites. The replication of VZV in MRC⁃5 and MRC⁃5IFNAR1⁃ cell lines was compared 168 h after VZV infection by using qRT⁃PCR and plaque formation unit（PFU）assay， to evaluate the effect of MRC⁃5IFNAR1⁃cell line on VZV replication. Results The growth status of MRC⁃5IFNAR1⁃ cell line wasconsistent with that of MRC ⁃ 5 cells，and the relative expression of IFNAR1 mRNA decreased by 73%；The relative expressions of IFNβ and OAS1 mRNA in MRC⁃5IFNAR1⁃ cell line were 61% and 90% lower than those in MRC⁃ 5 cells respectively after VZV infection；In addition，168 h after VZV infection，the level of DNA replication and the titer of VZV increased by 5. 7 folds and 4 folds respectively. Conclusion The successful establishment of MRC⁃5IFNAR1⁃ cell line may be a potential scheme to increase the yield of vaccines based on human diploid cells，and provided a reference for expanding production of VZV vaccine.

OBJECTIVES: To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates. METHODS: Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared. RESULTS: The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05). CONCLUSIONS The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.
Humans ; Infant, Newborn ; Bacteria ; China ; High-Throughput Nucleotide Sequencing ; Intestines ; Microbiota ; Pharynx/microbiology* ; RNA, Ribosomal, 16S/genetics*

Objective: To get insight into the current practice of noise reduction effect of workers as they wore hearing protectors in different domestic enterprises and the possible affected factors. Methods: From October 2020 to April 2021, using a random sampling method, 1197 workers exposed to noise in petrochemical factories, textile factories, and parts manufacturing factories were selected as the study subjects. The noise reduction effect of hearing protectors worn by workers in daily use was tested using a hearing protector suitability testing system. The personal sound attenuation level (PAR) was compared among workers in three enterprises, Targeted intervention and repetitive testing were conducted for workers who did not meet the noise reduction effect required by the enterprise, and the changes in PAR of workers before and after the intervention were compared. The comparison of baseline PARs between two or more groups was performed using the Mann Whitney test, the comparison of baseline PARs with post intervention PARs was performed using the Wilcoxon signed rank sum test, and the comparison of qualitative data between two or more groups was performed using the Chi square test. Results: The median baseline PAR for all workers was 15 dB. Men, age<30 years old, education level at or above college level, working experience of 5 to 15 years, and those who used hearing protectors for 5 to 15 years had higher PARs, with statistically significant differences (P<0.05). The median difference in baseline PAR among workers from three enterprises was statistically significant (H=175.06, P<0.01). The median PAR of subjects who did not pass the baseline increased from 3 dB to 21 dB after intervention (Z=-27.92, P<0.01) . Conclusion: Some workers wearing hearing protectors do not meet the required PAR, and low PARs may be related to incorrect wearing methods and incorrect selection of hearing protectors. As a tool for testing, training, and assisting in selection, the hearing protector suitability testing system is of great significance for worker hearing protection.
Male ; Humans ; Adult ; Hearing Loss, Noise-Induced/prevention & control* ; Ear Protective Devices ; Noise, Occupational/prevention & control* ; Hearing ; Audiometry

OBJECTIVES: To investigate the clinical application of metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) in the etiological diagnosis and treatment of refractory pneumonia (RTP) in children. METHODS: A retrospective analysis was performed on 160 children with RTP who were admitted to the Department of Pediatric Internal Medicine, Maternal and Child Health Hospital of Inner Mongolia Autonomous Region, from January 2020 to March 2023. According to whether mNGS was performed, they were divided into two groups: mNGS (n=80) and traditional testing (n=80). All children received the tests of inflammatory markers and pathogen tests after admission. Traditional pathogenicity tests included microbial culture (sputum specimen collected by suction tube), nucleic acid detection of respiratory pathogens, and serological test (mycoplasma, tuberculosis, and fungi). For the mNGS group, BALF specimens were collected after bronchoscopy and were sent to the laboratory for mNGS and microbial culture. The two groups were analyzed and compared in terms of the detection of pathogens and treatment. RESULTS: Compared with the traditional testing group, the mNGS group had a significantly higher detection rate of pathogens (92% vs 58%, P<0.05), with more types of pathogens and a higher diagnostic rate of mixed infections. Compared with the traditional testing group, the mNGS group had a significantly higher treatment response rate and a significantly lower incidence rate of complications during hospitalization (P<0.05). Treatment was adjusted for 68 children in the mNGS group according to the results of mNGS, with a treatment response rate of 96% (65/68) after adjustment. CONCLUSIONS Compared with traditional pathogen tests, BALF mNGS can significantly improve the detection rate of pathogens and find some rare pathogens. In clinical practice, when encountering bottlenecks during the diagnosis and treatment of children with RTP, it is advisable to promptly perform the mNGS to identify the pathogens.
Humans ; Child ; Bronchoalveolar Lavage Fluid ; Retrospective Studies ; Pneumonia/therapy* ; High-Throughput Nucleotide Sequencing ; Bronchoscopy ; Sensitivity and Specificity