This study investigated the primary pathogenesis and syndrome evolution of different heart failure with preserved ejection fraction(HFpEF)stages based on the classical and clinical experience of traditional Chinese medicine(TCM),combined with the clinical characteristics of pre-heart failure,symptomatic heart failure,and advanced heart failure.This study summarizes and refines the three core syndrome factors:water,deficiency and blood stasis.Water-fluid retention was observed throughout these three stages,from the beginning to the end.With the advancement of the disease,the heart yang changes from stagnation to deficiency,water-fluid retention gradually increases,blood stasis becomes increasingly prominent,and the disease location develops dynamically from the upper to the middle and lower jiao.This study proposes three methods of treating HFpEF.The main pathogenesis of pre-heart failure is lung qi dysfunction-induced water retention,which can be treated by dispersing lung qi and transforming water retention using Fuling Xingren Gancao Decoction.The primary pathogenesis of symptomatic heart failure is yang and qi deficiency-induced water retention,which can be treated with tonifying yang,supplementing qi,and transforming water retention using Shengxian Decoction combined with Linggui Zhugan Decoction.The primary pathogenesis of advanced heart failure is yang deficiency with blood stasis and water retention affecting the heart,which can be treated with tonifying yang,circulating blood,and expelling water retention using Zhenwu Tingli Decoction.Chinese medicine can be flexibly added or subtracted according to the patients'concurrent patterns.However,the daily care of patients should be considered.This study explores the staging treatment of HFpEF from water,deficiency and blood stasis to provide a TCM clinical reference for treating HFpEF.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To investigate the association of sleep disorders with the development and progression of nonalcoholic fatty liver disease(NAFLD).Methods A total of 1 868 participants from the health examination cohort and fatty liver cohort of Beijing Friendship Hospital from June 2022 to June 2023 were enrolled as subjects.Related data were collected from all subjects,including age,sex,education level,chronic medical history,and biochemical parameters,and all subjects completed Pittsburgh Sleep Quality Index(PSQI)scale independently.According to the diagnostic criteria,the subjects were divided into non-NAFLD group with 1 122 subjects and NAFLD group with 746 subjects,and according to the stage of progression,the patients in the NAFLD group were further divided into simple fatty liver group(SFL group with 624 subjects)and nonalcoholic steatohepatitis(NASH)group with 122 subjects.A one-way analysis of variance or the Kruskal-Wallis H test was used for comparison of continuous data between three groups.The chi-square test was used for comparison of categorical data between the three groups.The binary Logistic regression analysis was used to investigate the association between sleep factors and NAFLD,and the multinomial Logistic regression analysis was used to investigate the association between sleep factors and the different stages of NAFLD;two multivariate models were constructed for adjustment of potential confounding factors,i.e.,an age-sex adjustment model and a multivariate adjustment model,and the multivariate adjustment model adjusted the factors of age,sex,education level,smoking,diabetes,hypertension,body mass index(BMI),triglyceride(TG),and high-density lipoprotein cholesterol(HDL-C).Results There were significant differences in age,sex,BMI,education level,smoking,diabetes,hypertension,alanine aminotransferase,TG,and HDL-C between the non-NAFLD,SFL,and NASH groups(all P<0.05).There were also significant differences between the three groups in the total score of PSQI scale and the proportion of subjects with a score of 0—3 points for the 7 sleep components(all P<0.05).The multivariate adjustment model showed no significant association between sleep disorders and SFL,while long sleep latency(odds ratio[OR]=4.04,95%confidence interval[CI]:2.33—7.03,P<0.001),short sleep duration(OR=3.53,95%CI:1.83—6.82,P<0.001),and severe sleep disorders(OR=2.96,95%CI:1.48—5.93,P=0.002)were closely associated with the risk of NASH.Conclusion Overall sleep condition and its components of sleep disorders are not significantly associated with the simple fatty liver;however,long sleep latency,short sleep duration,and severe sleep disorders can increase the risk of NASH,which should be taken seriously in clinical practice.

Objective The occurrence of chickenpox in rapidly developing areas poses substantial seasonal risk to children.However,certain factors influencing local chickenpox outbreaks have not been studied.Here,we examined the relationship between spatial clustering,heterogeneity of chickenpox outbreaks,and socioeconomic factors in Southern China. Methods We assessed chickenpox outbreak data from Southern China between 2006 and 2021,comprising both relatively fast-growing parts and slower sub-regions,and provides a representative sample of many developing regions.We analyzed the spatial clustering attributes associated with chickenpox outbreaks using Moran's I and local indicators of spatial association and quantified their socioeconomic determinants using Geodetector q statistics. Results There were significant spatial heterogeneity in the risk of chickenpox outbreaks,with strong correlations between chickenpox risk and various factors,particularly demographics and living environment.Furthermore,interactive effects among specific are factors,such as population density and per capita residential building area,percentage of households with toilets,percentage of rental housing,exhibited q statistics of 0.28,0.25,and 0.24,respectively. Conclusion This study provides valuable insights into the spatial dynamics of chickenpox outbreaks in rapidly developing regions,revealing the socioeconomic factors affecting disease transmission.These implications extend the formulation of effective public health strategies and interventions to prevent and control chickenpox outbreaks in similar global contexts.

Objective:To investigate the neuroprotective effect of hesperidin combined with enriched environment on ferroptosis in collagenase-induced intracerebral hemorrhage(ICH) mouse model as well as the ferroptosis mechanism.Methods:ICH model was established by injecting collagenase Ⅶ into caudate putamen nucleus. Ninty C57BL/6J mice were randomly divided into 6 groups according to a random number table: sham group, intracerebral hemorrhage group, enriched environment group, hesperidin group, enriched environment and hesperidin group (combination group), and combination group + Nrf2 specific inhibitor ML385 (inhibitor group), with 15 mice in each group. The mice in inhibitor group, intracerebral hemorrhage group, enriched environment group, hesperidin group and combination group were injected with 0.5 μL collagenase type Ⅶ solution (0.075 U/μL, dissolved with 0.9% NaCl solutin) for ICH modeling, and the mice in sham group were injected with 0.9% normal saline. The hesperidin group, combination group, and inhibitor group were given hesperidin solution (dissolved in 0.5% carboxymethyl cellulose sodium) by gavage within 6 hours after the modeling surgery. The sham group, intracerebral hemorrhage group, and enriched environment group were given equal volumes of 0.5% carboxymethyl cellulose sodium solution by gavage. The inhibitor group was intraperitoneally injected with Nrf2 specific inhibitor ML385 (30 mg/kg, dissolved in 5% DMSO), while the other groups were intraperitoneally injected with an equal volume of 5% DMSO. Both gastric perfusion and intraperitoneal injection were completed within 6 hours after the end of modeling operation, once a day for 14 days. After the postoperative recovery of the mice, the enriched environment group, combination group, and inhibitor group were placed in enriched environment cages, while the sham group, intracerebral hemorrhage group, and hesperidin group were placed in regular cages. After all intervention were completed, all mice were evaluated using the modified neurological severity score (mNSS). Then the mice were subjected to brain water content detection, Prussian blue staining, ELISA detection of changes in malondialdehyde (MDA), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione peroxidase 4 (Gpx4), PCR and Western blot detection of nuclear factor E2 related factor 2 (Nrf2) and Gpx4 at the mRNA level and protein level. The GraphPad Prism 9 software was used for statistical analysis. ANOVA was used for multi-group comparison, and Tukey test was used for multiple comparisons.Results:(1) There was a statistically significant difference in mNSS scores among the 6 groups ( F=66.35, P<0.001). The mNSS score of the intracerebral hemorrhage group(8.00±1.46) was higher than that of the sham group(0.86±0.83)( P<0.05). The mNSS scores of the enriched environment group (6.47±1.13) and hesperidin group (6.13±1.25) were lower than that of the intracerebral hemorrhage group, but higher than that of the combination group (4.53±1.30)(all P<0.05). (2) There was a statistically significant difference in the percentage of brain water content among the 6 groups ( F=33.29, P<0.001). The percentage of brain water content in the intracerebral hemorrhage group was higher than that in the sham group.The percentage of brain water content in the enriched environment group and hesperidin group were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group (all P<0.05). (3) The result of Prussian blue staining showed that iron deposition in the intracerebral hemorrhage group was higher than that in the sham group, while the iron depositions in the enriched environment group and hesperidin groups were lower than that in the intracerebral hemorrhage group, but higher than that in the combination group(all P<0.05). (4) There were statistically significant differences in the expression levels of Nrf2 and Gpx4 mRNA and protein among the 6 groups ( F=27.73, 31.24, 26.79, 13.79, all P<0.001). The mRNA and protein levels of Nrf2 and Gpx4 in the combination group were higher than those in the enriched environment group, hesperidin group, but higher than those in the inhibitor group(all P<0.05). (5) The results of ELISA showed that the levels of MDA, Gpx4, ROS, and SOD in the brain tissues of 6 groups were statistically significant ( F=111.20, 21.53, 29.45, 22.75, all P<0.001). Among them, the MDA and ROS in the combination group ((14.05±0.57) nmol/mL, (75.46±3.40) ng/mL) were lower than those in the enriched environment group ((18.17±2.51) nmol/mL, (97.23±3.43) ng/mL), hesperidin group ((17.24±0.68) nmol/mL, (90.02±9.46) ng/mL) and the inhibitor group ((17.08±0.64) nmol/mL, (101.07±3.38) ng/mL), while Gpx4 and SOD ((340.40±31.21) pg/mL, (62.55±2.81) ng/mL) were higher than those in the enriched environment group ((267.81±27.17) pg/mL, (50.47±8.38) ng/mL), hesperidin group ((271.55±34.36) pg/mL, (50.55±8.19) ng/mL) and the inhibitor group ((235.65±72.54)pg/mL, (52.67±3.56)ng/mL)(all P<0.05). Conclusion:Enriched environment and hesperidin can inhibit ferroptosis after ICH by activating the Nrf2/GPX4 pathway, exerting neuroprotective effects on ICH mouse models, and the combined treatment of the enriched environment and hesperidin has a more significant effect.

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore-ductase(NR)and bioactivate aristolochic acid Ⅰ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS① Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2 μmol·L-1 for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC50)was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25 μmol·L-1)+AA-Ⅰ 0.2 and 1.0 μmol·L-1 for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L-1 small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0 μmol·L-1 for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L-1 human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS ①The IC50 of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42 μmol·L-1,respec-tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).② Luteolin≥5 μmol·L-1 significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰ under anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU-SION AKR1A1 is involved in AA-Ⅰ bioactivation,providing a reference for elucidation of the carcino-genic mechanism of AA-Ⅰ.

【Objective】 To analyze the correlation between CT attenuation value of renal papilla and occurrence and development of renal calculi. 【Methods】 The clinical data of 100 patients with calcium oxalate stones treated during Aug.2020 and Jul.2022 were retrospectively analyzed, including 60 with primary stones, and 40 with recurrent stones. The 30 healthy volunteers were enrolled in the control group. CT attenuation value of renal papilla was measured with plain scan CT, and risk factors were identified with the receiver operating characteristic (ROC) curve. The correlation of CT attenuation value and 24 h urine metabolism was analyzed. 【Results】 The CT attenuation value of renal papilla was significantly higher in the primary group [34.92 (IQR: 3.84)] and recurrent group [43.00 (IQR: 8.74)] than in the control group [32.58 (IQR: 5.21)] (P<0.05). Compared with the primary group, the recurrent group had decreased citric acid level but increased calcium level in 24 h urine (P<0.05). The citrate ion and calcium ion were correlated with the CT attenuation value (P<0.05). 【Conclusion】 Patients with high renal papilla density have a high risk of stone formation and recurrence. Increased renal papilla density is a warning signal for the development of stones. The high calcium and low citric acid in 24 h urine have certain effects on the occurrence and development of urolithiasis. Intake of calcium should be limited and citric acid should be supplemented in patients with calcium oxalate stones.

Ischemic stroke (IS) is a severe cerebrovascular disease with a high incidence, mortality, and disability rate. The first-line treatment for IS is the use of recombinant tissue plasminogen activator (r-tPA). Regrettably, numerous patients encounter delays in treatment due to the narrow therapeutic window and the associated risk of hemorrhage. Traditional Chinese medicine (TCM) has exhibited distinct advantages in preventing and treating IS. TCM enhances cerebral microcirculation, alleviates neurological disorders, regulates energy metabolism, mitigates inflammation, reduces oxidative stress injuries, and inhibits apoptosis, thereby mitigating brain damage and preventing IS recurrence. This article summarizes the etiology, pathogenesis, therapeutic strategies, and relationship with modern biology of IS from the perspective of TCM, describes the advantages of TCM in the treatment of IS, and further reviews the pharmacodynamic characteristics and advantages of TCM in the acute and recovery phases of IS as well as in post-stroke complications. Additionally, it offers valuable insights and references for the clinical application of TCM in IS prevention and treatment, as well as for the development of novel drugs.

Objective:To explore the clinical value of semi-ex vivo intestinal autotrans-plantation (IATx) for patients with mesenteric root regional tumors accompanied by vascular invasion.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 6 patients who underwent semi-ex vivo IATx in the Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital from September 2021 to December 2022 were collected. There were 4 males and 2 females, aged (47±21)years. Observation indicators: (1) surgical conditions; (2) postoperative conditions; (3) follow-up. Measurement data with normal distribution were represented by Mean± SD. Count data were represented by absolute numbers. Results:(1) Surgical conditions. All 6 patients completed semi-ex vivo IATx successfully. The operation time, warm ischemia time, cold ischemia time, volume of intraoperative blood transfusion were (10.2±2.1)hours, (2.3±1.6)minutes, (49.2±15.6)minutes, (707±263)mL. Of the 6 patients, 3 patients were intraoperatively perfused with cold UW solution, while the other 3 were not. (2) Postoperative conditions. Results of postoperative pathological examination of the 6 patients showed 4 cases of pancreatic ductal adenocarcinoma, 1 case of cholangiocarcinoma, and 1 case of mesenteric fibromatosis. All 6 cases had nega-tive surgical margins and the duration of postoperative hospital stay was (19±4)days. None of the patient had gastrointestinal bleeding or anastomotic leakage postoperatively, and the autotransplanted intestine functioned well. There was no perioperative death, and intravenous rehydration was not required after discharge. (3) Follow-up. All 6 patients were followed up for (12±5)months. Only 1 patient with mesenteric fibromatosis had recurrence in the 7th month postoperatively, while the remaining 5 patients showed no sign of recurrence or metastasis. There were 4 of 6 patients with chronic diarrhea. They were improved after oral loperamide, bifidobacterium and pancreatin capsules. All 6 patients survived.Conclusion:Semi-ex vivo IATx for the treatment of patients with mesenteric root regional tumors accompanied by vascular invasion is safe and feasible, which can achieve good short-term efficacy.

Objective:To understand the epidemiological characteristics of public health emergency events (PHEE) of varicella in China from 2006 to 2021 and related response performances.Methods:The data of varicella PHEE in 31 provinces of China from 2006 to 2021 were collected through the Public Health Emergency Management Information System, Microsoft Excel 2019 software and SPSS 26.0 statistical software were used to conduct descriptive epidemiological, statistical analysis on the time, area, location distribution, scale and epidemic management.Results:A total of 11 443 PHEE involving 341 048 related cases were reported from 2006 to 2021, with an annual attack rate of 1.78%-3.80% and a total attack rate of 2.33% (341 048/14 624 042). The number of PHEE and related cases of varicella decreased from 1 107 (35 349) in 2007 to 262 (6 884) in 2012 ( Z=-2.40, P<0.001), then increased year by year to 1 318 (42 649) in 2019 ( Z=2.58, P<0.001), with a significant decline since 2020. The varicella PHEE in China presents the seasonal characteristics,the peak is from April to June and from October to December, respectively. The sub-peak of varicella PHEE in eastern China generally appears 1-2 months earlier than in central and western China. Varicella PHEE reports are mainly distributed in eastern China, the attack rate is relatively high in western China, school-reported varicella PHEE was 88.26% of the total reports (10 099/11 443). The epidemic scale of varrcella PHEE typically range from 10 to 29 cases per year among the given outbreaks. The M ( Q1, Q3) of average number of cases, average duration, and average reporting interval of PHEE were 23 (16,35), 20 (14, 26) days, and 9 (5,19) days, respectively, and the reporting interval was positively correlated with the duration ( r=0.854, P<0.001). Conclusions:The varicella PHEE in China from 2006 to 2021 has not been effectively controlled. Schools are the key places to prevent and control varicella PHEE. Improving the sensitivity of varicella PHEE monitoring, strengthening the timely disposal of varicella epidemic, and promoting varicella vaccination are effective measures to prevent and control varicella PHEE.