BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.

OBJECTIVE: To elucidate the specific mechanisms by which electroacupuncture (EA) alleviates anxiety and fear behaviors associated with posttraumatic stress disorder (PTSD), focusing on the role of lipocalin-2 (Lcn2). METHODS: The PTSD mouse model was subjected to single prolonged stress and shock (SPS&S), and the animals received 15 min sessions of EA at Shenmen acupoint (HT7). Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear. Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex (PFC). Additionally, the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology. RESULTS: Mice subjected to SPS&S presented increased anxiety- and fear-like behaviors. Lcn2 expression in the PFC was significantly upregulated following SPS&S, leading to increased expression of the proinflammatory cytokines tumor necrosis factor-α and interleukin-6 and suppression of PFC neuronal activity. However, EA at HT7 inhibited Lcn2 release, reducing neuroinflammation and hypoexcitability in the PFC. Lcn2 overexpression mitigated the effects of EA at HT7, resulting in anxiety- and fear-like behaviors. CONCLUSION EA at HT7 can ameliorate PTSD-associated anxiety and fear, and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC. Please cite this article as: Yang YD, Zhong W, Chen M, Tang QC, Li Y, Yao LL, et al. Electroacupuncture alleviates behaviors associated with posttraumatic stress disorder by modulating lipocalin-2-mediated neuroinflammation and neuronal activity in the prefrontal cortex. J Integr Med. 2025; 23(5):537-547.
Electroacupuncture ; Stress Disorders, Post-Traumatic/metabolism* ; Animals ; Lipocalin-2/metabolism* ; Prefrontal Cortex/physiopathology* ; Male ; Mice ; Neurons/physiology* ; Disease Models, Animal ; Fear ; Behavior, Animal ; Mice, Inbred C57BL ; Neuroinflammatory Diseases/metabolism* ; Anxiety/therapy* ; Acupuncture Points

Small RNAs (sRNAs), the key components of RNA interference (RNAi) or RNA silencing, can mediate cell-autonomous gene silencing and function as signaling molecules across species. Microbe-induced gene silencing (MIGS), which is based on interspecies RNAi, is an effective approach for controlling fungal diseases in crops. The enolase gene VdEno is essential for the growth and development of the fungal pathogen Verticillium dahliae, which causes cotton Verticillium wilt. In this study, we engineered Trichoderma harzianum (Th) to express the double-stranded RNA (dsRNA) targeting VdEno. The engineered strain Th-VdEnoi successfully generated VdEno-specific small interfering RNA (siVdEno). We further confirmed that Th-VdEnoi effectively induced VdEno silencing at the translational level. The results of crop protection assays revealed that the cotton plants co-inoculated with V. dahliae (strain V592) and Th-VdEnoi presented significantly reduced disease severity and lower fungal biomass in their roots than the control plants inoculated with V. dahliae alone or with V. dahliae and Th-GFPi (a control strain expressing GFP-targeting dsRNA). Collectively, our findings demonstrate that VdEno is an effective target for controlling cotton Verticillium wilt and confirm that MIGS is a promising strategy for managing soil-borne fungal pathogens in crops. MIGS provides strong technical support for reducing the application of conventional chemical pesticides, developing eco-friendly biopesticides, and facilitating the sustainable development of agriculture.
Gossypium/microbiology* ; Plant Diseases/prevention & control* ; Gene Silencing ; Ascomycota/genetics* ; RNA Interference ; RNA, Double-Stranded/genetics* ; Hypocreales/genetics* ; RNA, Small Interfering/genetics* ; Verticillium/genetics* ; Fungal Proteins/genetics*

Objective:To investigate the mechanism of DNA damage and repair in MLL-rearranged acute myeloid leukemia(MLL-r AML)cells by the combination of Chidamide and the BRD4 inhibitor(+)-JQ-1.Methods:MLL-r AML cell lines Molm-13,MV4-11 and non-MLL-r AML cell line Kasumi were divided into control group(contr),Chidamide group(chida),(+)-JQ-1 group and Combination group(combi),respectively.Cell viability of Molm-13 was measured by CCK-8 to determine optimal the concentrations of Chidamide and(+)-JQ-1.The cell cycle was detected by flow cytometry,and apoptosis-related factors Bcl-2,Bax and caspase-3 were detected by Western blot.DNA damage marker γH2AX was detected by immunofluorescence.The protein expressions of DNA damage factor γH2AX,DNA damage checkpoint kinases p-ATR,p-CHK1,p-ATM,p-CHK2 and DNA damage repair factors Rad51 and 53BP1 were detected by Western blot.The expression of DNA damage repair factors Rad51 and 53BP1 mRNA was detected by qRT-PCR.Results:Under the treatment of Chidamide(300 nmol/L)and(+)-JQ-1(400 nmol/L),the proportion of G1 phase cells in MLL-r AML cell lines Molm-13 and MV4-11 was increased in combination group compared with control group.In non-MLL-r AML cell line Kasumi,compared with control group,the proportion of G1 phase cells in combination group was increased(P＜0.05).In Molm-13 and MV4-11 cell lines,compared with control group,the expression level of DNA damage marker γH2AX in combination group was increased(P＜0.05).The expression levels of DNA damage checkpoint and damage repair factors p-ATR,p-CHK1,p-ATM,p-CHK2,Rad51,53BP1 were decreased(P＜0.05).In Kasumi cell line,compared with control group,there was no significant change in the expression of some of the above factors in combination group(P＞0.05),but the expression trend of some factors was opposite.In MLL-r AML cell lines Molm-13 and MV4-11,compared with control group,the expression levels of Bax and caspase-3 protein were increased in combination group,while the expression levels of Bcl-2 protein were decreased(P＜0.05).In non-MLL-r AML cell line Kasumi,there was no significant change in apoptotic factor protein expression in combination group compared with control group(P＞0.05).Conclusion:Chidamide combined with(+)-JQ-1 can inhibit the proliferation of MLL-r AML cells,inhibit the initiation of protective self-repair of these leukemia cells by inhibiting the DNA damage response pathway,and ultimately increase the apoptosis of these cells,but non-MLL-r AML cells have no similar results.

Objective:To analyze the construction of human resources in specialized public health institutions in China,with a view to providing reference for strengthening the construction of human resources in public health in China.Methods:Based on the data of China Health and Wellness Statistical Yearbook,descriptive statistical analysis,Gini coefficient and health resource agglomeration were used to analyze the quantity and quality of human resources in specialized public health institutions and the equity of human resource allocation in different regions of China from 2012 to 2021.Results:From 2012 to 2021,the average annual growth rate of the number of specialized public health institution personnel nationwide was 4.10%,and the average annual growth rate of the number of specialized public health institution personnel per 1 000 population was 3.71%.In 2021,the Gini coefficient of human resources in China's specialized public health institutions allocated by population was 0.1002,and the Gini coefficient of the allocation of human resources according to the geographic area was 0.6706,and 21 provinces'health resource agglomeration value were greater than 1.Conclusion:the total amount of human resources in China's specialized public health institutions has steadily increased during the decade,and the quality has been greatly improved,but there is still a gap with the expected development goal;the development of human resources in different specialized public health institutions is not balanced;demographic fairness is better than geographic fairness in the allocation of human resources in public health,and there are significant inter-provincial differences.

Iron is indispensable for the viablility of nearly all living organisms, and it is imperative for cells, tissues, and organisms to acquire this essential metal sufficiently and maintain its metabolic stability for survival. Disruption of iron homeostasis can lead to the development of various diseases. There is a robust connection between iron metabolism and infection, immunity, inflammation, and aging, suggesting that disorders in iron metabolism may contribute to the pathogenesis of arthritis. Numerous studies have focused on the significant role of iron metabolism in the development of arthritis and its potential for targeted drug therapy. Targeting iron metabolism offers a promising approach for individualized treatment of arthritis. Therefore, this review aimed to investigate the mechanisms by which the body maintains iron metabolism and the impacts of iron and iron metabolism disorders on arthritis. Furthermore, this review aimed to identify potential therapeutic targets and active substances related to iron metabolism, which could provide promising research directions in this field.

AIM To establish an HPLC method for the simultaneous content determination of spinosin,ferulic acid,rosmarinic acid,salvianolic acid B,schisandrin A,schizandrin B and schisandrol A in Anshen Capsules.METHODS The analysis was performed on a 30℃thermostatic Inertsustain C18 column(5 μm,4.6 mm×250 mm),with the mobile phase comprising of methanol-acetonitrile-0.1%phosphoric acid flowing at 1.0 mL/min in a gradient elution manner,and the detection wavelengths were set at 203,270 nm.Subsequently,principal component analysis and partial least squares discriminant analysis were made.RESULTS Seven constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 96.12%-102.70%with the RSDs of 0.31%-1.83%.Ten batches of samples were divided into two categories according to manufacturers,and peaks 5(schisandrol A),4(salvianolic acid B)were quality difference markers.CONCLUSION This simple,sensitive,specific and reproducible method can be used for the quality control of Anshen Capsules.

Objective To report a case of synovial sarcoma of the liver and review the literature for improving the understanding of the disease.Methods The clinical data of a patient with liver synovial sarcoma admitted to the First Affiliated Hospital of Henan University were analyzed retrospectively.The imaging,pathological features,treatment and prognosis of this disease were summarized by searching the database(CNKI,Wanfang Data,PubMed,untill July 2022)and the literature results analyzed comprehensively.Results The patient was a 71-year-old female who was admitted to the hospital due to abdominal pain.Computed tomography(CT)scan showed a mass with mixed density in the right lobe and caudate lobe of the liver.The large cross section size was about 115 mm×87 mm and the mass showed continuous heterogeneous enhancement,being considered as malignant hepatic tumors with multiple metastasis of the liver and lung.Ultrasound-guided needle biopsy was performed,and microscopy showed the tumor cells were obvious atypical,and some were spindle-shaped.Immunohistochemistry showed that the patient was positive for vimentin(VIM),epithelial membrane antigen(EMA),methylation of histone at lysine 27(H3K27Me3),and negative for pan cytokeratin(CK-pan)and S-100,and pathological diagnosis of synovial sarcoma was made.The patient did not undergo subsequent treatment and was lost to follow-up after discharge.A total of 12 cases of hepatic synovial sarcoma were reported after searching the database.The clinical manifestations were abdominal pain or distention.The lesions were mostly located in the right lobe of the liver,usually large,heterogeneous density,and heterogeneous enhancement on enhanced CT or magnetic resonance imaging(MRI).Spindle-shaped cells were found at histopathologic examination.Immunohistochemistry showed the patient was positive for VIM,EMA,H3K27Me,B-cell leukemia/lymphoma-2(BCL-2)and transducer-like enhancer of split 1(TLE1).SS18-SSX fusion gene or SS18 gene isolation were detected.Eleven patients received surgical treatment,5 received adjuvant chemotherapy,and 4 had recurrence or metastasis during the follow-up period.Conclusions Synovial sarcoma of the liver is a rare malignant tumor of the liver.The clinical and imaging features are not specific.The diagnosis depends on pathology.At present,the main treatment is surgery,and comprehensive treatment such as adjuvant chemotherapy can be performed.The prognosis of the patient is poor.