This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

OBJECTIVE: To evaluate the short-term clinical efficacy of external fixation and internal fixation with steel plate in the treatment of unstable distal radius fractures (AO-23C type), based on the principles of Chinese osteosynthesis (CO). METHODS: Forty-eight patients with unstable distal radius fractures between January 2022 and February 2023 were retrospectively analyzed and divided into the CO external fixation group and internal fixation group. CO external fixation group consisted of 25 patients, including 7 males and 18 females, aged from 37 to 56 years old with an average of ( 52.6±11.3) years old. Among them, there were 7 patients of traffic accidents and 18 patients of falls, resulting in a total of 25 patients of closed fractures and no open fractures, the treatment was conducted using closed reduction and CO external fixation. The internal fixation group consisted of 23 patients, comprising 8 males and 15 females, age ranged from 41 to 59 years old, with an average age of(53.3±13.7) years old. Among them, 8 patients resulted from car accidents while the remaining 15 patients were caused by falls. All 23 patients were closed fractures without any open fractures observed. The technique of open reduction and internal fixation with steel plate was employed. The perioperative data, including injury-operation time, operation duration, blood loss, and length of hospital stay, were assessed in both groups. Additionally, the QuickDASH score and visual analogue scale (VAS) were evaluated. Range of motion and grip strength assessment, imaging findings such as palmar inclination angle, ulnar declination angle, radius length, articular surface step, intra-articular space measurements were also examined along with any complications. RESULTS: The follow-up duration ranged from 0 to 24 months, with an average duration of (16.0±3.8) months. The CO external fixation exhibited significantly shorter time from injury to operation (2.4±3.3) d vs (7.4±3.7) d, shorter operation duration (56.27±15.23) min vs (74.10±5.26) min, lower blood loss (14.52±6.54) ml vs (32.32±10.03) ml, and reduced hospitalization days (14.04±3.24 )d vs (16.45±3.05) d compared to the internal fixation group (P<0.05). The QuickDASH score at 12 months post-operation was (8.21±1.64) in the CO external fixation group, while no significant difference was observed in the internal fixation group (7.04±3.64), P>0.05. There were no statistically significant differences in VAS between two groups at 6 weeks, as well as 1 and 3 months post-surgery (P>0.05). Additionally, there were no significant disparities observed in terms of range of motion and grip strength between two groups at the 2-year follow-up after the operation (P>0.05). After 12 months of surgery, the CO external fixation group exhibited a significantly smaller palmar inclination angle (17.90±2.18) ° vs (19.87±3.21) °, reduced articular surface step (0.11±0.03) mm vs (0.17±0.02) mm, and shorter radius length (8.16±1.11) mm compared to the internal fixation group (9.59±1.02) mm, P<0.05. The ulnar deviation angle and intra-articular space did not show any significant difference between two groups (P>0.05). The reduced fell within the allowable range between the CO external fixation group (23 out of 25 cases) and the internal fixation group (21 out of 23 cases) was not statistically significant (P=0.29). There was no significant difference in complications between the two groups(P>0.05). CONCLUSION Both the CO external fixation and open reduction with plate internal fixation demonstrate clinical efficacy in managing unstable distal radius fractures. The CO external fixation offers advantages in shorter injury-to-operation times, reduced intraoperative blood loss, and decreased surgical durations, while radial shortening is more effectively controlled by internal fixation.
Humans ; Male ; Female ; Middle Aged ; Radius Fractures/physiopathology* ; Adult ; Bone Plates ; Fracture Fixation, Internal/methods* ; External Fixators ; Retrospective Studies ; Fracture Fixation/methods* ; Wrist Fractures

Objective To investigate the diagnostic value of 4 novel inflammatory markers related to routine blood tests,namely neutrophil-to-lymphocyte ratio(NLR),red blood cell distribution width(RDW),hemoglobin-to-RDW ratio(HRR)and systemic immune-inflammation index(SII),in elderly patients with chronic cardiovascular disease(CVD)complicated with frailty.Methods Retrospectively analyze 110 patients with chronic stable CVD who were hospitalized in the cadre ward of cardiovascular medicine at the Air Force Characteristic Medical Center from January 2022 to June 2023.According to the assessment results of the Fried scale,they were divided into three groups:non-frailty group(Fried score=0,n=30),the pre-frailty group(Fried score 1 or 2,n=40)and frailty group(Fried score≥3,n=40).The differences in general information,the impairment rate of daily living activities,miniature nutritional assessment-short form(MNA-SF)scores,mini-mental state examination(MMSE)scores,and the indicators such as NLR,RDW,HRR,and SII among the three groups were compared.Spearman rank correlation was used to analyze the correlation between NLR,RDW,HRR,SII and frailty scores as well as each frailty indicator.Multivariate logistic regression analysis was performed to identify the independent risk factors for frailty in elderly patients with chronic CVD,and the receiver operating characteristic(ROC)curve was used to assess the clinical diagnostic value of NLR and HRR in elderly patients with chronic CVD complicated with frailty.Results Compared with non-frailty group and pre-frailty group,patients in frailty group were older,with higher impaired rates of daily living activities,NLR,RDW,and SII,and lower MNA-SF scores,MMSE scores,and HRR,and differences were statistically significant(P<0.05).Spearman rank correlation analysis showed that the frailty score was positively correlated with NLR(rs=0.354,P<0.001),and RDW(rs=0.448,P<0.001),negatively correlated with HRR(rs=-0.232,P=0.024),and had no significant correlation with SII(rs=0.144,P=0.167).Further analysis of the correlation between the above novel inflammatory markers and the 5 components of frailty showed that NLR was positively correlated with fatigue(rs=0.228,P=0.017),slowed walking speed(rs=0.299,P<0.001),and low physical function(rs=0.319,P<0.001);RDW was positively correlated with decreased grip strength(rs=0.321,P<0.001),slowed walking speed(rs=0.422,P<0.001),and low physical function(rs=0.246,P=0.001);and HRR was negatively correlated with slowed walking speed(rs=-0.230,P=0.025),and low physical function(rs=-0.299,P=0.003).Multivariate logistic regression analysis showed that MNA-SF score(OR=0.577,95%CI 0.342-0.973)was an independent protective factor for pre-frailty in elderly patients with chronic CVD(P<0.05);NLR(OR=7.866,95%CI 1.101-56.185)was an independent risk factor for frailty,while HRR(OR=0.344,95%CI 0.120-0.983)and MNA-SF score(OR=0.292,95%CI 0.146-0.580)were independent protective factors for frailty in elderly CVD patients(P<0.05).The area under the ROC curve of NLR and HRR for diagnosing frailty in elderly patients with chronic CVD were 0.778 and 0.749,respectively.Conclusion NLR and HRR have high clinical diagnostic value for frailty in elderly patients with chronic CVD,and are expected to become effective inflammatory markers for screening elderly patients with chronic CVD complicated with frailty.

Isocitrate dehydrogenase 1 (IDH1) R132H is the most common mutated gene in grade II-III gliomas and oligodendrogliomas. Instead of activating telomerase (a reverse transcriptase which using RNA as a template to extend telomere length), the majority of IDH1^R132H mutant glioma maintain telomere length through an alternative mechanism that relies on homologous recombination (HR), which is known as alterative lengthening of telomere (ALT).The phenotype of ALT mechanism include: ALT associated promyelocytic leukemia protein (PML) bodies (APBs); extrachromosomal telomeric DNA repeats such as C- and T-loops; telomeric sister chromatid exchange (T-SCE), etc. The mechanism of ALT activation is not fully understood. Recent studies have shown that mutation IDH1 contributes to ALT phenotype in glioma cells in at least three key ways. Firstly, the IDH1^R132H mutation mediates RAP1 down-regulation leading to telomere dysfunction, thus ensuring persistent endogenous telomeric DNA damage, which is important for ALT activation. Spontaneous DNA damage at telomeres may provide a substrate for mutation break-induced replication (BIR)‑mediated ALT telomere lengthening, and it has been demonstrated that RAP1 inhibits telomeric repeat-containing RNA, transcribed from telomeric DNA repeat sequences (TERRA) transcription to down-regulate ALT telomere DNA replication stress and telomeric DNA damage, thereby inhibiting ALT telomere synthesis. Similarly, in ALT cells, knockdown of telomere-specific RNaseH1 nuclease triggers TERRA accumulation, which leads to increased replication pressure. Overexpression of RNaseH1, on the other hand, attenuates the recombination capacity of ALT telomeres, leading to telomere depletion, suggesting that RAP1 can regulate the level of replication pressure and thus ALT activity by controlling TERRA expression. Secondly, the IDH1^R132H also alters the preference of the telomere damage repair pathway by down-regulating XRCC1, which inhibits the alternative non-homologous end joining (A-NHEJ) pathway at telomeres and alters cellular preference for the HR pathway to promote ALT. Finally, the IDH1^R132H has a decreased affinity for isocitric acid and NADP+ and an increased affinity for α ketoglutarate (α‑KG) and NADPH, so that the mutant IDH1^R132H catalyzes the hydrogenation of α‑KG to produce 2-hydroxyglutarate (2-HG)in a NADPH-dependent manner. Because 2-HG is structurally similar to α‑KG, which maintains the trimethylation level of H3k9me3 by competitively inhibiting the activity of the α‑KG-dependent histone demethylase KDM4B, and recruits heterochromatin protein HP1α to heterochromatinize telomeres, and promote ALT phenotypes in cooperation with the inactivating of ATRX. In addition, it has been shown that APBs contain telomeric chromatin, which is essentially heterochromatin, and HP1α is directly involved in the formation of APBs. Based on these studies, this article reviews the mechanism of IDH1^R132H mediated telomere dysfunction and the preference of DNA repair pathway at telomeres in cooperate with ATRX loss to promote ALT, which may provide references for clinical targeted therapy of IDH1^R132H mutant glioma.

To understand the distribution of ticks in the Wuwei Region,enrich tick species data,and provide a basis for the prevention of tick-borne diseases,tick were collected using flagging and tick-picking methods during the highest activity period from April to September in 2021 and 2022 in the mountainous areas of Wuwei City.The ticks were identified based on morpho-logical and molecular biological characteristics,and characteristic sequences were obtained.A systematic evolutionary tree was constructed using the neighbor-joining method in MEGA 11.0 software.In total,7 342 ticks collected in Wuwei,which be-longed to 5 species from 4 genera with in the Ixodidae family,which included Dermacentor nuttalli,Hyalomma asiaticum,Ixodes canisuga,Haemaphysalis longicornis and Haema-physalis danieli.Ticks of the same species clustered together into the same branch of an evolutionary tree.In the Wuwei Re-gion,five common tick species are found across various habi-tats,with each habitat featuring different distributions of tick species and populations.The Dermacentor nuttalli is the dom-inant tick species in this area.

Objective: To compare the predictive efficacy of the two thrombosis risk assessment scores (Padua and IMPEDE scores) in venous thromboembolism (VTE) within 6 months in patients with newly diagnosed multiple myeloma (NDMM) in China. Methods: This study reviewed the clinical data of 421 patients with NDMM hospitalized in Beijing Jishuitan Hospital from April 2014 to February 2022. The sensitivity, specificity, accuracy, and Youden index of the two scores were calculated to quantify the thrombus risk assessment of VTE by the Padua and IMPEDE scores. The receiver operating characteristics curves of the two evaluation scores were drawn. Results: The incidence of VTE was 14.73%. The sensitivity, specificity, accuracy, and Youden index of the Padua score were 100%, 0%, 14.7%, and 0% and that of the IMPEDE score was 79%, 44%, 49.2%, and 23%, respectively. The areas under the curve of Padua and IMPEDE risk assessment scores were 0.591 and 0.722, respectively. Conclusion: IMPEDE score is suitable for predicting VTE within 6 months in patients with NDMM.
Humans ; Venous Thromboembolism/etiology* ; Multiple Myeloma/diagnosis* ; Risk Assessment ; Risk Factors ; ROC Curve ; Retrospective Studies

Objective: To explore the value of cardiac magnetic resonance imaging (CMR) in the risk stratification of hypertrophic cardiomyopathy (HCM). Methods: HCM patients who underwent CMR examination in Fuwai Hospital between March 2012 and May 2013 were retrospectively enrolled. Baseline clinical and CMR data were collected and patient follow-up was performed using telephone contact and medical record. The primary composite endpoint was sudden cardiac death (SCD) or and equivalent event. The secondary composite endpoint was all-cause death and heart transplant. Patients were divided into SCD and non-SCD groups. Cox regression was used to explore risk factors of adverse events. Receiver operating characteristic (ROC) curve analysis was used to assess the performance and the optimal cut-off of late gadolinium enhancement percentage (LGE%) for the prediction of endpoints. Kaplan-Meier and log-rank tests were used to compare survival differences between groups. Results: A total of 442 patients were enrolled. Mean age was (48.5±12.4) years and 143(32.4%) were female. At (7.6±2.5) years of follow-up, 30 (6.8%) patients met the primary endpoint including 23 SCD and 7 SCD equivalent events, and 36 (8.1%) patients met the secondary endpoint including 33 all-cause death and 3 heart transplant. In multivariate Cox regression, syncope(HR=4.531, 95%CI 2.033-10.099, P<0.001), LGE% (HR=1.075, 95%CI 1.032-1.120, P=0.001) and left ventricular ejection fraction (LVEF) (HR=0.956, 95%CI 0.923-0.991, P=0.013) were independent risk factors for primary endpoint; Age (HR=1.032, 95%CI 1.001-1.064, P=0.046), atrial fibrillation (HR=2.977, 95%CI 1.446-6.131, P=0.003),LGE% (HR=1.075, 95%CI 1.035-1.116, P<0.001) and LVEF (HR=0.968, 95%CI 0.937-1.000, P=0.047) were independent risk factors for secondary endpoint. ROC curve showed the optimal LGE% cut-offs were 5.1% and 5.8% for the prediction of primary and secondary endpoint, respectively. Patients were further divided into LGE%=0, 0P<0.001) and the accumulated incidence of primary endpoint was 1.2% (2/161), 2.2% (2/89), 10.5% (16/152) and 25.0% (10/40), respectively. Conclusion: LGE is an independent risk factor for SCD events as well as all-cause death and heart transplant. LGE is of important value in the risk stratification in patients with HCM.
Humans ; Female ; Adult ; Middle Aged ; Male ; Contrast Media ; Retrospective Studies ; Stroke Volume ; Gadolinium ; Ventricular Function, Left ; Magnetic Resonance Imaging ; Cardiomyopathy, Hypertrophic/diagnostic imaging* ; Death, Sudden, Cardiac ; Risk Assessment

Objective To analyze the genetic subtypes of human immunodeficiency virus (HIV) and the prevalence of pretreatment drug resistance in the newly reported HIV-infected men in Guangxi. Methods The stratified random sampling method was employed to select the newly reported HIV-infected men aged≥50 years old in 14 cities of Guangxi from January to June in 2020.The pol gene of HIV-1 was amplified by nested reverse transcription polymerase chain reaction and then sequenced.The mutation sites associated with drug resistance and the degree of drug resistance were then analyzed. Results A total of 615 HIV-infected men were included in the study.The genetic subtypes of CRF01_AE,CRF07_BC,and CRF08_BC accounted for 57.4% (353/615),17.1% (105/615),and 22.4% (138/615),respectively.The mutations associated with the resistance to nucleoside reverse transcriptase inhibitors (NRTI),non-nucleoside reverse transcriptase inhibitors (NNRTI),and protease inhibitors occurred in 8 (1.3%),18 (2.9%),and 0 patients,respectively.M184V (0.7%) and K103N (1.8%) were the mutations with the highest occurrence rates for the resistance to NRTIs and NNRTIs,respectively.Twenty-two (3.6%) patients were resistant to at least one type of inhibitors.Specifically,4 (0.7%),14 (2.3%),4 (0.7%),and 0 patients were resistant to NRTIs,NNRTIs,both NRTIs and NNRTIs,and protease inhibitors,respectively.The pretreatment resistance to NNRTIs had much higher frequency than that to NRTIs (2.9% vs.1.3%;χ²=3.929,P=0.047).The prevalence of pretreatment resistance to lamivudine,zidovudine,tenofovir,abacavir,rilpivirine,efavirenz,nevirapine,and lopinavir/ritonavir was 0.8%, 0.3%, 0.7%, 1.0%, 1.3%, 2.8%, 2.9%, and 0, respectively. Conclusions CRF01_AE,CRF07_BC,and CRF08_BC are the three major strains of HIV-infected men≥50 years old newly reported in Guangxi,2020,and the pretreatment drug resistance demonstrates low prevalence.
Male ; Humans ; Middle Aged ; Reverse Transcriptase Inhibitors/therapeutic use* ; HIV Infections/drug therapy* ; Drug Resistance, Viral/genetics* ; China/epidemiology* ; Mutation ; HIV-1/genetics* ; Protease Inhibitors/therapeutic use* ; Genotype

Humans ; Receptors, Chimeric Antigen ; Hematopoietic Stem Cell Transplantation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Immunotherapy, Adoptive ; Antigens, CD19

Six new (1-6) and seven known depsidones (7-13) were isolated from the culture of an ant (Monomorium chinensis)-derived fungus Spiromastix sp. MY-1. Their structures were elucidated by extensive spectroscopic analysis including high resolution MS, 1D and 2D NMR data. The new bromide depsidones were obtained through supplementing potassium bromide in the fermentation medium of Spiromastix sp. MY-1. All isolated compounds showed various bioactivities against the tested phytopathogenic bacteria. Particularly, new bromide compound 4, named spiromastixone S, exhibited the strongest activity against Xanthomonas oryzae pv. oryzae with a MIC value of 5.2 μmol·^-1.
Animals ; Anti-Bacterial Agents ; Ants ; Bromides ; Depsides ; Fungi ; Lactones ; Microbial Sensitivity Tests ; Molecular Structure