Efficacy and safety of interventional therapy combined with drug injection under bronchoscope in the treatment of central non-small cell lung cancer / 中国临床药理学与治疗学

AIM: To evaluate the efficacy and safety of interventional therapy combined with tumor drug injection under bronchoscope for central non-small cell lung cancer (NSCLC). METHODS: Sixty-four patients who met the test admission criteria were randomly assigned to the experimental group and the control group according to the ratio of 1:1, and were given bronchoscopic interventional therapy combined with local drug injection of recombinant human endostatin combined with platinum-containing dual-drug chemotherapy and platinum-containing dual-drug alone, respectively. The curative efficiency and safety of the two groups were compared. RESULTS: Compared with the control group, the KPS score, dyspnea grading were significantly improved (P<0.05). The effective rate of the test group was 78.12%, which was higher than 37.5% in the control group, the difference between the two groups was significant (P<0.05). Moreover, there was also a significant difference in the 1-year survival rate between the experimental group and the control group (P<0.05). CONCLUSION: The treatment of central NSCLC by interventional therapy combined with tumor drug injection through fiberoptic bronchoscope has obvious clinical efficacy, which can effectively alleviate the clinical symptoms and improve the quality of life of patients. There is no significant difference in adverse reactions between the two groups, and is worthy of popularization and application.

Establishment and genotype identification of hepatic stellate cell-specific Grk2 gene knockout mouse model / 中国药理学通报

Aim To establish a stable hepatic stellate cell ( HSC ) -specific G protein-coupled receptor kinase 2 ( GRK2 ) knockout mice and provide the important animal model for further studying the biological function of GRK2 in HSC. Methods The loxP-labeled Grk2 gene mouse (Grk2

High-throughput screening of novel TFEB agonists in protecting against acetaminophen-induced liver injury in mice

Macroautophagy (referred to as autophagy hereafter) is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and organelles. Previous studies showed that autophagy protects against acetaminophen (APAP)-induced injury (AILI) via selective removal of damaged mitochondria and APAP protein adducts. The lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with autophagosomes. In the present study, we showed that transcription factor EB (TFEB), a master transcription factor for lysosomal biogenesis, was impaired by APAP resulting in decreased lysosomal biogenesis in mouse livers. Genetic loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI, respectively. Mechanistically, overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2 (NRF2) activation to protect against AILI. We also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB agonists. Among these agonists, salinomycin, an anticoccidial and antibacterial agent, activated TFEB and protected against AILI in mice. In conclusion, genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

Etiological diagnostic value of metagenomic next-generation sequencing in peritoneal dialysis-related peritonitis / 中华肝脏病杂志

Objective: To explore the etiological diagnostic value of metagenomic next-generation sequencing (mNGS) in peritoneal dialysis (PD)-related peritonitis. Methods: The study was a retrospective cohort study. The clinical data of patients with PD-related peritonitis who were treated and underwent microbial cultivation and mNGS test at the same time from June 2020 to July 2021 in the Affiliated Drum Tower Hospital, Medical School of Nanjing University were analyzed. The positive rate, detection time and consistency between mNGS test and traditional microbial culture were compared. Results: A total of 18 patients with age of (50.4±15.4) years old and median dialysis time of 34.0 (12.4, 62.0) months were enrolled in the study, including 11 males and 7 females. Pathogenic microorganisms were isolated in 17 patients by mNGS test, with a positive rate of 17/18, which was higher than 13/18 of microbial culture, but the difference was not statistically significant (P=0.219). Both mNGS test and microbial culture isolated positive pathogenic bacteria in 12 patients, and mNGS test isolated the same types of pathogenic bacteria as microbial cultivation did in 11 patients. In five patients with negative microbial culture, mNGS test also isolated pathogenic microorganisms, including 3 cases of Staphylococcus epidermidis, 1 case of Mycobacterium tuberculosis and 1 case of Ureaplasma urealyticum. In 1 patient, microbial culture isolated pathogenic bacteria (Escherichia coli) whereas mNGS test did not. The detection time of mNGS was 25.0 (24.0, 27.0) h, which was significantly shorter than 89.0 (72.8, 122.0) h of microbial culture (Z=3.726, P<0.001). Conclusions: mNGS test can improve the detection rate of pathogenic microorganisms in PD-related peritonitis and greatly shorten the detection time, and has good consistency with microbial culture. mNGS may provide a new approach for pathogen identification of PD-related peritonitis, especially refractory peritonitis.

Neuroprotective effect and mechanism of Zuogui Jiangtang Jieyu Formula on diabetes mellitus complicated with depression model rats based on CX3CL1-CX3CR1 axis / 中国中药杂志

Based on the CX3C chemokine ligand 1(CX3CL1)-CX3C chemokine receptor 1(CX3CR1) axis, this study explored the potential mechanism by which Zuogui Jiangtang Jieyu Formula(ZGJTJY) improved neuroinflammation and enhanced neuroprotective effect in a rat model of diabetes mellitus complicated with depression(DD). The DD rat model was established by feeding a high-fat diet combined with streptozotocin(STZ) intraperitoneal injection for four weeks and chronic unpredictable mild stress(CUMS) combined with isolated cage rearing for five weeks. The rats were divided into a control group, a model group, a positive control group, an inhibitor group, and a ZGJTJY group. The open field test and forced swimming test were used to assess the depression-like behaviors of the rats. Enzyme-linked immunosorbent assay(ELISA) was performed to measure the expression levels of the pro-inflammatory cytokines interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) in plasma. Immunofluorescence staining was used to detect the expression of ionized calcium-binding adapter molecule 1(Iba1), postsynaptic density protein-95(PSD95), and synapsin-1(SYN1) in the hippocampus. Hematoxylin-eosin(HE) staining, Nissl staining, and TdT-mediated dUTP nick end labeling(TUNEL) fluorescence staining were performed to assess hippocampal neuronal damage. Western blot was used to measure the expression levels of CX3CL1, CX3CR1, A2A adenosine receptor(A2AR), glutamate receptor 2A(NR2A), glutamate receptor 2B(NR2B), and brain-derived neurotrophic factor(BDNF) in the hippocampus. Compared with the model group, the ZGJTJY group showed improved depression-like behaviors in DD rats, enhanced neuroprotective effect, increased expression of PSD95, SYN1, and BDNF(P<0.01), and decreased expression of Iba1, IL-1β, and TNF-α(P<0.01), as well as the expression of CX3CL1, CX3CR1, A2AR, NR2A, and NR2B(P<0.01). These results suggest that ZGJTJY may exert its neuroprotective effect by inhibiting the CX3CL1-CX3CR1 axis and activation of hippocampal microglia, thereby improving neuroinflammation and abnormal activation of N-methyl-D-aspartate receptor(NMDAR) subunits, and ultimately enhancing the expression of synaptic-related proteins PSD95, SYN1, and BDNF in the hippocampus.

Expression of TLR3 in human adenocarcinoma of the lung cells induced by respiratory syncytial virus and its significance in the diagnosis of pneumonia in children / 中国医师杂志

Objective:To study the expression of Toll like receptor 3 (TLR3) in human adenocarcinoma of the lung cells induced by respiratory syncytial virus (RSV) and its significance in the diagnosis of pneumonia in children.Methods:A549 cells were divided into RSV infection group [added 1 μg/ml Lipopolysaccharide (TLR3 agonist) transfected RSV virus after 150 μl intervention], Lipopolysaccharide stimulation group (added 1 μg/ml Lipopolysaccharide 150 μl intervention) and normal control group (normal culture). The mRNA expressions of tumor necrosis factor-α, interleukin 8, TLR3 protein and TLR3 in A549 Cells of different groups were compared. We prospectively selected 80 children with RSV infectious pneumonia admitted to Baoding Second Central Hospital from August 2019 to October 2021 as the RSV pneumonia group, and sixty children with common pneumonia were taken as the common pneumonia group, and 60 healthy children in our hospital were taken as the control group. The mRNA expression of serum TLR3 in different groups was compared, and the diagnostic efficacy of serum TLR3 in RSV pneumonia was evaluated by receiver operating characteristic.Results:There was a statistically significant difference in the expression of TLR3 protein among different groups of A549 cells ( P<0.001). The expression differences of TLR3 mRNA in different groups of A549 cells at different time points were statistically significant(all P<0.001). There was significant difference in the expression of tumor necrosis factor-α and interleukin 8 of A549 cells at different time points in different groups (all P<0.05). There was a statistically significant difference in the expression of serum TLR3 mRNA among the three groups of subjects ( F=155.237, P<0.001). The critical value for TLR3 gene diagnosis was 66.87, with corresponding sensitivity of 73.75%, specificity of 70.83%, and the area under curve (AUC) of 0.803(95% CI: 0.753-0.855). Conclusions:Respiratory syncytial virus induces human lung cancer cells and promotes disease progression through TLR3 expression; Serum TLR3 can be used for the diagnosis of RSV pneumonia.

Mediating effects of self-perceptions of aging between frailty and cognitive function in community-dwelling older adults / 中华行为医学与脑科学杂志

Objective:To explore the mediating role of self-perceptions of aging between frailty and cognitive function in community-dwelling older adults.Methods:From February to July 2021, a total of 528 elderly people in Xinxiang community were investigated with the frailty phenotype, the brief self-perceptions ageing questionnaire and the Mini-mental state examination(MMSE) scale.According to the MMSE total score and education level, the subjects were divided into cognitive impairment group (illiteracy≤17, primary school≤20, junior high school and above≤24, n=74) and cognitive normal group( n=454). SPSS 25.0 software was used for common method deviation test, descriptive statistics and correlation analysis, while AMOS 24.0 software was used to build structural equation model and Bootstrap method was used for intermediary effect test. Results:(1)The prevalence of cognitive impairment among the elderly in the community was 14.1%. The differences between the cognitively normal group and cognitively impaired group were statistically significant in terms of age, education, number of chronic diseases suffered and depression ( χ2=59.21, 6.53, 9.84, 25.47, all P<0.05). The differences were statistically significant in terms of frailty( χ2=75.65, P<0.001) and self-perceptions of aging ( t=77.67, P<0.001). (2)Self-perceptions of aging in the cognitively impaired group (47.39±8.66) was higher than that in the cognitively normal group (38.22±8.24) ( t=77.67, P<0.001) .Frailty score in cognitively impaired group (2.00 (1.00, 3.00)) was higher than that in the cognitively normal group (0.00 (0.00, 1.00))( Z=-8.63, P<0.001) . (3)Frailty was negatively correlated with cognitive function ( r=-0.492, P<0.01), and positively correlated with self-perceptions of aging ( r=0.540, P<0.01). Self-perceptions of aging was negatively correlated with cognitive function ( r=-0.541, P<0.01) . After controlling the influencing factors such as age, education level, chronic diseases and depression, the correlation was still significant (all P<0.01) . (4) Self-perceptions of aging played a partially mediating role in the relationship between frailty and cognitive function, the mediating effect accounted for 58.5% of the total effect. Conclusion:Frailty and self-perceptions of aging have a significant impact on the cognitive function of the elderly in the community, and self-perceptions of aging plays a partial intermediary role between the frailty and cognitive function of the elderly in the community.

Effect and safety of double plasma molecular absorption in treatment of patients with severe wasp stings injury: a multicenter historical cohort study / 中华危重病急救医学

Objective:To compare the effect and safety of continuous veno-venous hemofiltration (CVVH)+double plasma molecular absorption (DPMA)+hemoperfusion (HP), CVVH+HP, and CVVH+plasma exchange (PE) in treatment of patient with severe wasp stings injury.Methods:Multicenter, historical cohort study and superiority test were used. From July 2020 to October 2022, patients with wasp sting injury and multiple organ damage admitted to the intensive care units (ICU) of five hospitals were consecutively screened and recruited into the CVVH+DPMA+HP group (intervention group). Propensity score matching was used to establish historical cohorts. Patients with severe wasp sting injury who hospitalized from January 2016 to June 2020 in each ICU were collected and matched 1∶1 with the intervention group, and divided into CVVH+HP group and CVVH+PE group according to their actual hemopurification protocols (historical control groups). The primary outcome was the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score on days 3 and 7 after initiation of treatment. Secondary outcomes included complications, length of ICU and hospital stays, and all-cause mortality. Multivariate Cox proportional risk regression was used to analyze the prognosis of patients.Results:After propensity score matching, 56 patients in intervention group and each of the two historical control groups were matched successfully. There were no significant differences in age, gender, comorbidities, biochemical test indices and critical illness scores among the groups. After treatment, APACHE Ⅱ score markedly declined in all groups, and the decrease was faster in the intervention group; treatment with DPMA [hazard ratio ( HR) = 1.04, 95% confidence interval (95% CI) was 1.02-1.08, P = 0.00], the decreased levels of body temperature ( HR = 1.02, 95% CI was 1.00-1.03, P = 0.02), serum creatine kinase (CK; HR = 0.98, 95% CI was 0.96-1.00, P = 0.05) and myoglobin (MYO; HR = 2.88, 95% CI was 1.24-6.69, P = 0.01) were independent risk factors for APACHE Ⅱ score decline to the target value (15 scores). There were no significant differences in the incidence of bleeding complications, filter or perfusion thrombosis, blood pressure reduction, catheter-related infection and anaphylaxis among the groups. Conclusion:CVVH+DPMA+HP regimen can significantly reduce the APACHE Ⅱ score of patients with severe wasp sting injury, and the efficacy is superior to CVVH+HP and CVVH+PE regimens, with safety.

Predictive value of multimodal magnetic resonance imaging based radiomics model for micro-satellite instability of rectal cancer / 中华消化外科杂志

Objective:To investigate the predictive value of multimodal magnetic resonance imaging (MRI) based radiomics model for microsatellite instability (MSI) of rectal cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 117 patients with rectal cancer who were admitted to 2 medical centers, including 74 in Ningbo Urology & Nephrology Hospital and 43 in the First Affiliated Hospital of Zhejiang University School of Medicine, from January 2020 to December 2022 were collected. There were 73 males and 44 females, aged (63±5)years. Based on random number table, all 117 patients were divided into the training dataset of 70 cases and the test dataset of 47 cases with a ratio of 7:3. All patients underwent pelvic MRI exami-nation. Observation indicators: (1) construction of radiomics prediction model and analysis of charac-teristics; (2) analysis of factors influencing MSI of rectal cancer in the training dataset; (3) construc-tion and evaluation of the prediction model for MSI of rectal cancer. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and compari-son between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate analysis was conducted using the one way ANOVA and multivariate analysis was conducted using the Logistic regression model with forward method. The receiver operating characteristic curve was drawn, and the area under the curve (AUC), decision curve, calibration curve and Delong test were used to evaluate the predictive ability of prediction model. Results:(1) Construction of radiomics prediction model and analysis of characteristics. Five thousand five hundred and eighty radiomics features were finally extracted from the 117 patients. Based on the feature selection using the maximum correlation minimum redundancy method, and the least absolute shrinkage and selection operator fitting algorithm, 9 radiomics features were finally selected. The radiomics prediction model was constructed based on calculation of the radiomics score. (2) Analysis of factors influencing MSI of rectal cancer in the training dataset. Results of multivariate analysis showed that platelet count was an independent influencing factor for MSI of rectal cancer [ odds ratio=1.13, 95% confidence interval ( CI) as 1.06-1.21, P<0.05]. (3) Construction and evaluation of the prediction model for MSI of rectal cancer. The clinical prediction model and clinical-radiomics combined prediction model were constructed based on the results of multivariate analysis. The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the training dataset was 0.94 (95% CI as 0.86-0.98), 0.96 (95% CI as 0.88-0.99), 0.99 (95% CI as 0.93-1.00), respectively, with the sensitivity and specificity as 90.7%, 91.2%, 96.9% and 85.0%, 88.9%, 94.3%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the clinical prediction model ( Z=2.20, P<0.05), and there was no significant difference between the radiomics prediction model and the clinical-radiomics combined prediction model or the clinical prediction model ( Z=1.94, 0.60, P>0.05). The AUC of clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model in the test dataset was 0.97 (95% CI as 0.88-1.00), 0.86 (95% CI as 0.73-0.95), 0.97(95% CI as 0.87-1.00), respectively, with the sensitivity and specificity as 99.3%, 95.8%, 99.3% and 85.7%, 73.9%, 90.5%. Results of Delong test showed that there was a significant difference in the predictive performance between the clinical-radiomics combined prediction model and the radiomics prediction model ( Z=2.21, P<0.05), and there was no significant difference between the clinical prediction model and the clinical-radiomics combined prediction model or the radiomics prediction model ( Z=0.17, 1.82, P>0.05). Results of calibration curve showed that clinical prediction model, radiomics prediction model, clinical-radiomics combined prediction model had good ability in predicting the MSI status of rectal cancer. Results of decision curve showed that compared to clinical prediction model and radiomics prediction model, clinical-radiomics combined prediction model had greatest net gain in predicting the MSI of rectal cancer. Conclusion:The prediction model based on 9 radiomics features after selecting can effectively predict the MSI status of rectal cancer, and the clinical-radiomics combined prediction model has a better prediction efficiency.

Progress in surgical treatment of infantile spasms / 中华实用儿科临床杂志

Infantile spasms(IS) is the prevalent epilepsy syndrome in infancy, characterized by an early age of onset, distinctive seizure type, hypsarrhythmia on electroencephalography, and psychomotor retardation.Despite the fact that medication therapy is the primary treatment for IS, there are still some children with IS who are resistant to drug therapy, which is extremely detrimental to their prognosis.Therefore, surgical therapy has increasingly become one of the most prominent IS treatments.As of now, the indications, preoperative evaluation, and surgical techniques of surgery are continuously being investigated based on variables such as the disease, etiology, age, etcetera.The effect of surgery on cognitive function, physical function, linguistic capacity, and memory function is gaining increasing interest.This article described the indications, preoperative evaluation, surgical procedures (including resection, palliative surgery, and stereotactic surgery), and postoperative efficacy of surgical treatment for IS, with the goal of improving the prognosis of IS through precise surgical treatment, and providing more treatment options and a good long-term prognosis for children with drug-resistant IS.

Discussion on medication law of Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on ancient and modern medical case cloud platform / 国际中医中药杂志

Objective:To discuss the medication law in prescriptions of Professor Shao Nianfang in the treatment of kidney deficiency and bone marrow loss in senile dementia based on data mining.Methods:Medical cases of kidney deficiency and bone marrow loss in senile dementia in the Geriatric Hospital of Shandong University of Traditional Chinese Medicine from 1st Jan. 2014 to 31st Oct, 2019 were collected. Through hospital electronic medical records system prescription statistics, using ancient and modern medical case cloud platform (V1.2.4), medication frequency, property ans taste, efficacy analysis, correlation rule analysis, clustering analysis and complex network analysis were performed.Results:Totally 110 cases were included in medical cases, involving 238 kinds of Chinese materia medica. The top 10 Chinese materia medica with use frequency were Poria, Acori Tatarinowii Rhizoma, Corni Fructus, Dioscoreae Rhizoma, Rehmanniae Radix Praeparata, Alpiniae Oxyphyllae Fructus, Rehmanniae Radix, Astragali Radix, Chuanxiong Rhizoma, Atractylodis Macrocephalae Rhizoma; the properties were mainly mild, warm slight cold, and cold; the tastes were mainly sweet, bitter, pungent, and light; the meridians were mainly spleen, liver, lung and kidney meridians; the efficacy was clearing dampness and promoting diuresis, clearing heat and promoting blood circulation, calming mind, clearing heat and detoxification, reducing dampness and promote appetizing, tonifying spleen; the association analysis found 15 groups of drug combinations used more than 25 times, they were: Corni Fructus and Poria, Corni Fructus and Dioscoreae Rhizoma, Dioscoreae Rhizoma and Corni Fructus, Rehmanniae Radix Praeparata and Corni Fructus, Dioscoreae Rhizoma and Poria, Astragali Radix and Poria, Alismatis Rhizoma and Poria, Moutan Cortex and Poria, Rehmanniae Radix Praeparata and Poria, Rehmanniae Radix and Poria, Polygalae Radix and Acori Tatarinowii Rhizoma, Moutan Cortex and Corni Fructus, Moutan Cortex and Dioscoreae Rhizoma, Alismatis Rhizoma and Corni Fructus, Alismatis Rhizoma and Dioscoreae Rhizoma; clustering analysis identified four groups of new prescriptions, the first group: Poria, Rehmanniae Radix, Rehmanniae Radix Praeparata, Alismatis Rhizoma, Moutan Cortex, Corni Fructus, Dioscoreae Rhizoma; the second group: Acori Tatarinowii Rhizoma, Cistanches Herba, Morindae Officinalis Radix; the third group: Alpiniae Oxyphyllae Fructus, Chuanxiong Rhizoma, Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle; the fourth group: Atractylodis Macrocephalae Rhizoma, Codonopsis Radix, Astragali Radix, Angelicae Sinensis Radix; the results of complex network analysis showed that the core prescription was modified Liuwei Dihuang Pills. Conclusion:This study found that in view of kidney deficiency and bone marrow loss in senile dementia, Professor Shao pays attention to strengthening the healthy qi, and focuses on tonifying deficiency, taking into account the methods of clearing dampness, clearing heat, detoxification, removing blood stasis and restoring consciousness. The four new prescriptions found in the study can provide a reference for modified medication for syndrome differentiation.

Efficacy Evaluation of Apparent Diffusion Coefficient in the Treatment of Uterine Fibroid by Magnetic Resonance Guided Focused Ultrasound Surgery / 中山大学学报(医学科学版)

ObjectiveTo assess the value of apparent diffusion coefficient （ADC） in the treatment of uterine fibroid using magnetic resonance guided focused ultrasound surgery （MRgFUS）. MethodsThe MRI and clinical data of 56 patients with uterine fibroid before， at 3 and 6 months after MRgFUS treatment， at Foshan Hospital of Traditional Chinese Medicine from December 2018 to October 2022， were retrospectively analyzed. The correlation between the ADC value and lesion volume， symptoms severity score （SSS） and uterine fibroid symptoms quality of life questionnaire （UFS-QOL） were analyzed. ANOVA was used to compare the differences in related parameters before and after treatment， and Pearson’s method was performed to analyze data correlation. ResultsThere were significant differences in ADC value ［（1.11±0.13）， （1.84±0.09）， （2.12±0.24），×10-3/（mm2/s）］， lesion volume （102±35.30， 56.70±18.88， 46.93±18.99，cm3）， SSS （36.73±11.74， 21.77±10.21， 17.66±9.30） and UFS-QOL score （59.05±17.48， 76.54±16.50， 82.46±12.37） between before treatment and each time point after treatment （F value was 557.837， 73.589， 53.976 and 37.606， respectively， all P<0.05）. The ADC values were negatively correlated with lesion volume and SSS， and positively correlated with UFS-QOL score， with correlation coefficients of -0.586， -0.630 and 0.592， respectively （all P<0.05）. ConclusionThe ADC value has clinical significance for the treatment of uterine fibroid using MRgFUS.

Analysis of the nail microbiome in patients with onychomycosis by high-throughput sequencing of 16S rDNA and internal transcribed spacer regions / 中华皮肤科杂志

Objective:To investigate differences in bacterial and fungal microbiome between infected nails and healthy nails among patients with onychomycosis.Methods:Nail scraping samples were collected from infected nails and healthy nails of 31 patients with onychomycosis, who visited Dalian Dermatosis Hospital from August 2020 to July 2021. The total DNA of nail microbiota was extracted, and the V3-V4 regions of the bacterial 16S rDNA gene and the fungal internal transcribed spacer (ITS) region were amplified and sequenced using Illumina technology. The USEARCH and mothur softwares were used for data cluster analysis to obtain the operational taxonomic units (OTUs) , Wilcoxon rank sum test was used to analyze α diversity, analysis of similarities (ANOSIM) was performed to analyze β diversity, linear discriminant analysis of effect size (LEfSe) was performed to evaluate the species difference.Results:Among the 31 patients with onychomycosis, 16 were males and 15 were females. According to the age, they were divided into young group (18 - 35 years old, 10 cases) , middle-aged group (36 - 60 years old, 11 cases) , and elderly group (over 60 years old, 10 cases) . As the α-diversity analysis revealed, the infected nail group showed significantly decreased Shannon index ( W = 290, P = 0.007) , but significantly increased Simpson index ( W = 663, P = 0.010) compared with the healthy nail group, suggesting that the diversity and evenness of bacterial communities were lower in the infected nail group than in the healthy nail group; however, there was no significant difference in the diversity of fungal communities between the infected nail group and healthy nail group. The β-diversity analysis based on the unweighted-UniFrac distance matrix showed no significant difference in the fungal or bacterial community composition between the infected nail group and healthy nail group (bacterial communities: R = 0.0052, P = 0.331; fungal communities: R = 0.0036, P = 0.337) ; the β-diversity analysis based on the weighted-UniFrac distance matrix showed significant differences in the abundance of bacterial and fungal communities between the two groups (both P = 0.001) . In terms of the species composition, the bacterial flora with significantly decreased abundance in the infected nail group compared with the healthy nail group included Bacteroidetes, Proteobacteria, Betaproteobacteria, Burkholderiales, Ralstonia, Sphingomonas and Streptococcus, while the abundance of Bacilli, Bacillales and Staphylococcus was significantly higher in the infected nail group than in the healthy nail group. Compared with the healthy nail group, the fungal flora with significantly increased abundance in the infected nail group included Eurotiomycetes, Onygenales, Leotiomycetes-ord-incertae-sedis, Arthrodermataceae, Periconia, Erysiphe, Tilletiopsis, Trichophyton, Erysiphe cruciferarum, Trichophyton rubrum, Malassezia sympodialis, while the abundance of Saccharomycetes, Saccharomycetales, Saccharomycetaceae, Dothioraceae, Candida and Alternaria was significantly lower in the infected nail group than in the healthy nail group. Conclusion:The diversity and abundance of bacterial communities significantly differed between infected nails and healthy nails among patients with onychomycosis, while only the abundance of fungal communities differed between the two groups, and perhaps there was correlations between some bacterial and fungal communities.

Efficacy and safety evaluation of the regimen containing Bedaquiline in elderly patients with drug-resistant pulmonary tuberculosis / 中华老年医学杂志

Objective:To evaluate the efficacy and adverse reactions of the regimen containing Bedaquiline in elderly patients with multi-drug resistant tuberculosis.Methods:From March 2019 to June 2022, patients with multi-drug resistant pulmonary tuberculosis admitted to Anhui Chest Hospital were randomly divided into two groups: the observation group was given a treatment containing Bedaquiline, and the control group was given a treatment without Bedaquiline.Patients were also divided into elderly patients(age ≥60 years old)and non-elderly patients(age <60 years old)according to age.Sputum culture conversion, lesion absorption and adverse reactions were compared between the observation group and the control group in general, elderly and non-elderly patients, respectively.Results:A total of 170 cases were collected, including 79 in the observation group and 91 in the control group.Sputum culture conversion: The sputum culture conversion rates of observation groups in general, non-elderly and elderly patients were better than that of control groups at the 3rd month after treatment(the general, 96.2% vs.75.8%, χ2=14.001, P<0.001; the non-elderly, 94.9% vs.82.1%, χ2=4.675, P=0.031; the elderly, 100.0% vs. 65.7%, χ2=8.771, P=0.003), and at the 6th month, the rates of overall observation group was better than that of control group(98.7% vs.92.3%, χ2=3.895, P=0.048); the rates of non-elderly and elderly observation group and control group were all greater than 90%, with no statistical significance( P>0.05). Lesion absorption: Overall and non-elderly observation groups were better than control group in lesion absorption at the 3rd month(the general, 84.8% vs.68.1%, χ2=12.962, P=0.002; the non-elderly, 88.1% vs.71.4%, χ2=9.832, P=0.007; and the 6th month(the general, 88.6% vs.76.9%, χ2=14.888, P=0.001; the non-elderly, 89.8% vs.82.1%, χ2=8.618, P=0.013). The focal absorptivity of senile observation group at the end of March and June were 75.0% and 85.0%, respectively, both better than control group, but the difference was not statistically significant( P>0.05). Adverse reactions: Overall and non-senile observation groups had longer QT interval than control groups( P<0.05), but no patients stopped bedaquiline because of this, and there was no significant difference in QT interval between the two groups( P>0.05). Conclusions:In elderly patients with multi-drug resistant pulmonary tuberculosis, early sputum culture conversion turns fast after treatment with Bedaquiline, which has good therapeutic effect, good tolerance and controllable adverse reactions.

Association of serum biomarkers with frailty in elderly hospitalized patients / 中华老年医学杂志

Objective:To evaluate the association of different biomarkers with frailty in elderly hospitalized patients.Methods:In this cross-sectional study, a total of 319 elderly patients aged 65 years or older hospitalized in Beijing Hospital between September 2018 and February 2019 were enrolled.Patients had a mean age of(75.0±6.6)years and 151(47.3%)were women.Based on the Fried phenotype, patients were divided into a non-frail group(244 cases, 76.5%)and a frail group(75 cases, 23.5%). The clinical characteristics and biomarker levels of the two groups were compared.The association of different biomarkers with frailty was evaluated by using the receiver operating characteristic(ROC)curve.The Youden index was used for the optimal cutoff values and the area under the curve(AUC)were calculated.AUCs of different biomarkers were compared to assess their correlations with frailty.Results:Hemoglobin, lipid levels(triglycerides, total cholesterol and low-density lipoprotein cholesterol), and prealbumin were significantly lower in the frail group than in the non-frail group( P<0.05), while N-terminal pro-B type natriuretic peptide(NT-proBNP)and high-sensitivity C reactive protein(hsCRP)levels were significantly higher than in the non-frail group( P<0.05). Thyrotropin(TSH)and free triiodothyronine(FT3)levels were significantly lower( P<0.05)and trans-triiodothyronine(rT3)was significantly higher( P<0.05)in the frail group.The combination of six biomarkers[hemoglobin, prealbumin, hsCRP, 25-dihydroxy vitamin D3[25(OH)D3], rT3 and NT-pro BNP]had the most powerful correlation with frailty(AUC=0.705, 95% CI: 0.652-0.755), but the correlation was not significantly different from that of the combination of 3 markers(hemoglobin, rT3 and hsCRP)(ROC=0.010, 95% CI: -0.0106-0.0306, P>0.05). Either of the two combinations was significantly better than the combination of 2 markers(hemoglobin and rT3)(ROC=0.143, 95% CI: 0.0406-0.245; ROC=0.153, 95% CI: 0.0498-0.256; all P<0.01). Conclusions:Hemoglobin, lipids, prealbumin, TSH and FT3 levels decrease while NT-proBNP and hsCRP levels increase in elderly hospitalized frail patients.The 6-biomarker combination[hemoglobin, prealbumin, hsCRP, 25(OH)D3, rT3 and NT-pro BNP]and 3-biomarker combination(hemoglobin, rT3 and hsCRP)have better correlation with frailty than the 2-biomarker combination(hemoglobin and rT3).

Comparison of frailty assessment and related tools in elderly hospitalized patients with atrial fibrillation / 中华老年医学杂志

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Depression status of elderly patients with metabolic syndrome in three provinces of China / 中华流行病学杂志

Objective: To understand the depression status and its influencing factors in elderly patients with MS in China and to explore the correlation between various components of elderly MS and depression. Methods: This study is based on the "Prevention and Intervention of Key Diseases in Elderly" project. We used a multi-stage stratified cluster random sampling method to complete 16 199 elderly aged 60 years and above in 16 counties (districts) in Liaoning, Henan, and Guangdong Provinces in 2019, excluding 1 001 missing variables. Finally, 15 198 valid samples were included for analysis. The respondents' MS disease was obtained through questionnaires and physical examinations, and the respondents' depression status within the past half month was assessed using the PHQ-9 Depression Screening Scale. The correlation between elderly MS and its components and depression and its influencing factors were analyzed by logistic regression. Results: A total of 15 198 elderly aged 60 years and above were included in this study, with the prevalence of MS at 10.84% and the detection rate of depressive symptoms in MS patients at 25.49%. The detection rates of depressive symptoms in patients with 0, 1, 2, 3, and 4 MS abnormal group scores were 14.56%, 15.17%, 18.01%, 25.21%, and 26.65%, respectively. The number of abnormal components of MS was positively correlated with the detection rate of depressive symptoms, and the difference between groups was statistically significant (P<0.05). The risk of depression symptoms in patients with MS, overweight/obesity, hypertension, diabetes, and dyslipidemia was 1.73 times (OR=1.73, 95%CI:1.51-1.97), 1.13 times (OR=1.13, 95%CI:1.03-1.24), 1.25 times (OR=1.25, 95%CI:1.14-1.38), 1.41 times (OR=1.41, 95%CI:1.24-1.60), 1.81 times (OR=1.81,95%CI:1.61-2.04), respectively, more than those without the disease. Multivariate logistic regression analysis showed that the detection rate of depressive symptoms in patients with sleep disorders was higher than that with normal sleep (OR=4.89, 95%CI: 3.79-6.32). The detection rate of depressive symptoms in patients with cognitive dysfunction was 2.12 times higher than that in the average population (OR=2.12, 95%CI: 1.56-2.89). The detection rate of depressive symptoms in patients with impaired instrumental activities of daily living (IADL) was 2.31 times (OR=2.31, 95%CI: 1.64-3.26) higher than that in the average population. Tea drinking (OR=0.73, 95%CI: 0.54-0.98) and physical exercise (OR=0.67, 95%CI: 0.49-0.90) seemed to be protective factors for depression in elderly MS patients (P<0.05). Conclusions: Older patients with MS and its component abnormalities have a higher risk of depression than the average population. Sleep disorders, cognitive impairment, and IADL impairment are important influencing factors for depression in elderly MS patients, while tea drinking and physical exercise may help to reduce the risk of the disease.

A descriptive analysis of hyperlipidemia in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hyperlipidemia in adult twins in the Chinese National Twin Registry (CNTR) and explore the effect of genetic and environmental factors on hyperlipidemia. Methods: Twins recruited from the CNTR in 11 project areas across China were included in the study. A total of 69 130 (34 565 pairs) of adult twins with complete information on hyperlipidemia were selected for analysis. The random effect model was used to characterize the population and regional distribution of hyperlipidemia among twins. The concordance rates of hyperlipidemia were calculated in monozygotic twins (MZ) and dizygotic twins (DZ), respectively, to estimate the heritability. Results: The age of all participants was (34.2±12.4) years. This study's prevalence of hyperlipidemia was 1.3% (895/69 130). Twin pairs who were men, older, living in urban areas, married,had junior college degree or above, overweight, obese, insufficient physical activity, current smokers, ex-smokers, current drinkers, and ex-drinkers had a higher prevalence of hyperlipidemia (P<0.05). In within-pair analysis, the concordance rate of hyperlipidemia was 29.1% (118/405) in MZ and 18.1% (57/315) in DZ, and the difference was statistically significant (P<0.05). Stratified by gender, age, and region, the concordance rate of hyperlipidemia in MZ was still higher than that in DZ. Further, in within-same-sex twin pair analyses, the heritability of hyperlipidemia was 13.04% (95%CI: 2.61%-23.47%) in the northern group and 18.59% (95%CI: 4.43%-32.74%) in the female group, respectively. Conclusions: Adult twins were included in this study and were found to have a lower prevalence of hyperlipidemia than in the general population study, with population and regional differences. Genetic factors influence hyperlipidemia, but the genetic effect may vary with gender and area.

A descriptive analysis on hypertension in adult twins in China / 中华流行病学杂志

Objective: To describe the distribution characteristics of hypertension among adult twins in the Chinese National Twin Registry (CNTR) and to provide clues for exploring the role of genetic and environmental factors on hypertension. Methods: A total of 69 220 (34 610 pairs) of twins aged 18 and above with hypertension information were selected from CNTR registered from 2010 to 2018. Random effect models were used to describe the population and regional distribution of hypertension in twins. To estimate the heritability, the concordance rates of hypertension were calculated and compared between monozygotic twins (MZ) and dizygotic twins (DZ). Results: The age of all participants was (34.1±12.4) years. The overall self-reported prevalence of hypertension was 3.8%(2 610/69 220). Twin pairs who were older, living in urban areas, married, overweight or obese, current smokers or ex-smokers, and current drinkers or abstainers had a higher self-reported prevalence of hypertension (P<0.05). Analysis within the same-sex twin pairs found that the concordance rate of hypertension was 43.2% in MZ and 27.0% in DZ, and the difference was statistically significant (P<0.001). The heritability of hypertension was 22.1% (95%CI: 16.3%- 28.0%). Stratified by gender, age, and region, the concordance rate of hypertension in MZ was still higher than that in DZ. The heritability of hypertension was higher in female participants. Conclusions: There were differences in the distribution of hypertension among twins with different demographic and regional characteristics. It is indicated that genetic factors play a crucial role in hypertension in different genders, ages, and regions, while the magnitude of genetic effects may vary.