BACKGROUND: Chronic kidney disease (CKD) poses a major global health challenge, often foreshadowing poor patient outcomes. The C-reactive protein to albumin ratio (CAR) serves as a pivotal biomarker, demonstrating a strong correlation with adverse outcomes in cardiovascular disease (CVD). This study sought to examine the correlation between CAR and the risk of all-cause and cardiovascular mortality in patients with CKD stages 3-5. METHODS: This study utilized data of CKD patients from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2010, with follow-up to December 31, 2019. The optimal CAR cutoff value was identified utilizing the method of maximally selected rank statistics. Multivariable Cox proportional hazards regression model, restricted cubic splines (RCS) model, and subgroup analysis were employed to assess the association between CAR and mortality among CKD patients. RESULTS: During a median (with interquartile range) follow-up period of 115 (112,117) months among 2,841 CKD individuals, 1,893 deaths were observed, including 692 deaths due to CVD events. Based on the RCS analysis, a non-linear correlation was observed between CAR and mortality. Using 0.3 as the optimal CAR cutoff value, the cohort was divided into high and low groups. In the fully adjusted model, CKD patients with high CAR values exhibited an elevated risk of all-cause mortality (hazard ratio [HR] 1.53, 95% confidence interval [CI] 1.28-1.83, P < 0.001) and cardiovascular mortality (HR 1.48, 95% CI 1.08-2.02, P = 0.014). Compared to the population aged >65 years (HR 1.32, 95% CI 0.99-1.76, P = 0.064), the risk of cardiovascular mortality was significantly higher in those aged ≤65 years (HR 2.19, 95% CI 1.18-4.09, P = 0.014) with elevated CAR levels. CONCLUSIONS A notable correlation exists between the elevation of CAR and increased all-cause and cardiovascular mortality, suggesting its potential as an independent indicator for evaluating the prognosis of patients with CKD stages 3-5.
Humans ; Renal Insufficiency, Chronic/epidemiology* ; Cardiovascular Diseases/blood* ; Male ; Female ; Middle Aged ; C-Reactive Protein/metabolism* ; Aged ; Biomarkers/blood* ; Nutrition Surveys ; Adult ; United States/epidemiology* ; Serum Albumin/analysis*

OBJECTIVE To investigate the modulating effect of neotropics on form deprivation myopia(FDM)in guinea pigs.METHODS Tricolour guinea pigs were randomly divided into normal control group,FDM model group,FDM+saline group,FDM+atropine group,and FDM+neotropine group,with eight animals in each group.Except for the normal control group,the right eyes of the guinea pigs were covered for 14 d to establish a guinea pig FDM model.The drug administration groups were injected with 10 μL of saline,1%atropine,or 1%neotropine into the vitreous cavity once every other day.The changes in the refractive error and axial length of both eyes were recorded for 1 d before the intervention and for 14 d after the intervention.Then,the eyeballs of guinea pigs were taken from the right eyes.HE staining was used to evaluate the histopathological structure of the sclera while sirius red staining was used to detect the collagen protein content in the sclera.RT-qPCR was used to detect the mRNA expressions of transforming growth factor-β1(TGF-β1),matrix metalloproteinase(MMP-2)and tissue inhibitor of metalloproteinase(TIMP-2)in guinea pigs'sclera.The protein expression levels of collagen type Ⅰ(Col-Ⅰ)and TGF-β1 in guinea pig sclera were detected by Western blotting while those of MMP-2,TIMP-2 and Ki-67 were detected by immunohistochemical staining.RESULTS Compared with the nor-mal control group,eyes of guinea pig in the FDM model group showed a significantly lower refractive error(P<0.01),significant elongation of the ocular axis(P<0.01),scattered distribution of scleral fibre bundles,sparse collagen cells,reduced scleral thickness(P<0.01),and a significantly lower collagen protein content(P<0.01).The mRNA and protein expressions of TIMP-2 and TGF-β1 were lower(P<0.05,P<0.01),and MMP-2 was higher(P<0.01)in scleral tissue.The protein expression level of Col-Ⅰwas lower(P<0.05)while that of Ki-67 was elevated(P<0.01)in scleral tissue.Compared with the FDM model group,there were no significant changes in any of the indexes in the FDM+saline group.The refractive error of the right eyes of guinea pigs in the FDM+neotropium group and the FDM+atropium group were significantly higher(P<0.05),the length of the ocular axis was significantly shorter(P<0.05),the collagen fibres were arranged more tightly,the fibre bundles were distributed more orderly,the distribution of the collagen cells was more uniform,and the thickness of the sclera was significantly increased(P<0.01).Collagen protein contents were significantly higher(P<0.05,P<0.01),the mRNA and protein expressions of TIMP-2 and TGF-β1 were significantly higher(P<0.01),MMP-2 mRNA and protein expressions were significantly lower(P<0.05,P<0.01).The protein expression level of Col-Ⅰwas higher(P<0.05,P<0.01),and that of Ki-67 was lower(P<0.05,P<0.01)in scleral tissue.CONCLU-SION The muscarinic antagonist neotropine inhibits the development of myopia in guinea pigs in the FDM model by reversing both the down-regulation of TGF-β1 and the up-regulation of MMP-2 in scleral tissues and inhibiting the remodeling of the scleral extracellular matrix.

OBJECTIVE To explore the neuroprotective effect and possible mechanism of celastrol （Cel） and its derivatives （Cel-1， Cel-2） in terms of neuroinflammation and oxidative damage. METHODS Neuroinflammation model of microglial BV2 cells was induced by 1 μg/mL lipopolysaccharide （LPS）； oxidative damage model of human neuroblastoma SH-SY5Y cells was induced by 200 μmol/L hydrogen peroxide （H2O2）. The toxicity of different concentrations of Cel， Cel-1 and Cel-2 （0.625-20 μmol/L） to the two types of cells was investigated. The levels of nitric oxide （NO）， tumor necrosis factor α （TNF-α）， interleukin 1β （IL-1β）， and IL-6 in BV2 cells induced by LPS at safe concentrations （0.039-0.625 μmol/L） were all detected. The survival rate of SH-SY5Y cells induced by H2O2 was also determined. The expression levels of phosphoinositide 3-kinase （PI3K）， p-PI3K， protein kinase B （Akt）， p-Akt， cystatinase 3 （caspase-3）， B-cell lymphoma 2 （Bcl-2） and Bcl-2-related X protein （Bax） in SH- SY5Y cells induced by H2O2 at 0.156， 0.313， 0.625 μmol/L of active compound 2 were all detected. RESULTS In the concentration gradient range between 0.039 and 0.625 μmol/L， the results of neuroinflammation model experiments showed that Cel， Cel-1 and Cel-2 could reduce the contents of NO， TNF-α， IL-1β， and IL-6 in culture medium of BV2 cells （P＜0.05 or P＜ 0.01）； their IC50 values for neuroinflammation were （0.25±0.04）， （0.61±0.14） and （0.11±0.02） μmol/L respectively. Meanwhile， all of them could reverse the phenomenon of decreased cell survival rate after H2O2 treatment in the oxidative damage experiments at a certain concentration （P＜ 0.05 or P＜0.01）， with neuroprotective EC50 values of （0.43± XJC2023009） 0.08）， （0.45±0.04） and （0.28±0.03） μmol/L， respectively.Induced by H2O2， the phosphorylation of PI3K and Akt protein， protein expressions of Bcl-2 and Bcl-2/Bax ratio were all increased significantly （P＜0.05 or P＜0.01）， while the protein expressions of caspase-3 and Bax were decreased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS Cel， Cel-1， and Cel-2 all have significant neuroprotective activities at certain concentrations， and Cel-2 shows the most significant protective effect. The mechanism of action of Cel-2 may be related to regulating the PI3K/Akt and caspase-3/Bcl-2/Bax signaling pathways， reducing the inflammatory response， oxidative stress damage and inhibiting neuronal apoptosis.

OBJECTIVE: To analyze the outcome indexes of randomized controlled trials (RCTs) of acupuncture and moxibustion for mild cognitive impairment (MCI) so as to provide a reference for the protocol design and the construction of a core outcome set in relevant clinical trials of acupuncture and moxibustion for MCI. METHODS: From CNKI, Wanfang, VIP, SinoMed, PubMed, Cochrane Library, EMbase, and Web of Science, RCTs of acupuncture and moxibustion for MCI were searched, and the time duration was ranged from January 1st, 2018 to October 31th, 2023. The general information and outcome indexes of the included studies were collected and analyzed through literature screening and data extraction. RESULTS: A total of 46 studies were eligible, with 2 072 samples and 18 diagnostic criteria involved. The outcome indexes were categorized into 7 domains according to functional attributes, including clinical symptoms/signs, TCM symptoms/syndromes, physical and chemical examination, quality of life, psychiatric and mental health, safety assessment, and patient satisfaction. Eighty-four outcome indexes were reported, with the use frequency of 237. Currently, RCTs of acupuncture and moxibustion for MCI were limited in the big difference in neuropsychological assessment tool, the inadequate reports on educational degree/educational years, the diversity of physical and chemical detection indexes, the inconsistency of the time points for outcome evaluation, the insufficient application of primary and secondary outcomes, the lack of the application of TCM diagnosis, pattern/syndrome differentiation and outcomes, and the shortage in long-term prognosis and economic assessment. CONCLUSION It is recommended to specify and develop the core outcome set of acupuncture and moxibustion for MCI to advance the standardization of related research design, the rational selection of outcome indexes, and the reliability of the research results.
Humans ; Acupuncture Therapy ; Cognitive Dysfunction/therapy* ; Moxibustion ; Quality of Life ; Randomized Controlled Trials as Topic ; Treatment Outcome

OBJECTIVE: To explore the strategy of pregnancy-preserving and maternal- fetal management in patients with primary gynecologic neuroendocrine tumors (gNETs) during pregnancy. METHODS: We performed whole genome sequencing (WGS) for analyzing maternal and fetal somatic and germline single nucleotide variations (SNVs) and small insertions and deletions (InDels) for a 29-year-old pregnant woman diagnosed with stage IB2 large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the cervix. A systematic literature review was performed to explore the strategies for treatment of such rare histological type while maintaining pregnancy. RESULTS: Global case analysis of cervical NETs during pregnancy suggested that negative lymph node metastasis and an early FIGO stage were potentially associated with a good prognosis of the patients. In the case presented herein, a pregnancy-preserving strategy was adopted and favorable maternal-fetal outcomes were achieved after neoadjuvant chemotherapy, radical surgery and postoperative systemic chemotherapy. At 35 CONCLUSIONS Although gNETs in pregnancy are rare and highly risky, pregnancy-preserving managements of gNETs can still be considered and favorable maternalfetal outcomes are possible with proper assessment of the clinical indications and implementation of multimodal treatments. Precise treatment and follow-up strategies based on the results of WGS for risk-reducing intervention of cancer recurrence or occurrence can potentially benefit the patient and the neonate.
Adenocarcinoma ; Adult ; Carcinoma, Neuroendocrine/genetics* ; Child ; Female ; Humans ; Infant, Newborn ; Neoplasm Recurrence, Local ; Pregnancy ; Uterine Cervical Neoplasms/genetics*

Advances in high-throughput sequencing (HTS) have fostered rapid developments in the field of microbiome research, and massive microbiome datasets are now being generated. However, the diversity of software tools and the complexity of analysis pipelines make it difficult to access this field. Here, we systematically summarize the advantages and limitations of microbiome methods. Then, we recommend specific pipelines for amplicon and metagenomic analyses, and describe commonly-used software and databases, to help researchers select the appropriate tools. Furthermore, we introduce statistical and visualization methods suitable for microbiome analysis, including alpha- and beta-diversity, taxonomic composition, difference comparisons, correlation, networks, machine learning, evolution, source tracing, and common visualization styles to help researchers make informed choices. Finally, a step-by-step reproducible analysis guide is introduced. We hope this review will allow researchers to carry out data analysis more effectively and to quickly select the appropriate tools in order to efficiently mine the biological significance behind the data.

Objective:To investigate the variation characteristics and influencing factors of HIV/AIDS subtypes in Wuxi city of Jiangsu Province from 2014 to 2016.Methods:HIV/AIDS population in Wuxi city in 2014 was selected as the research object, and the HIV molecular epidemiology and follow-up study were carried out. Collect epidemiological information, extract DNA from blood samples, amplify pol gene fragment by nest-PCR and sequence, use ChromasPro 1.6 software and MEGA 7.0 software to construct the HIV-1 sequence database, and use FastTree2.1.10 software to construct the phylogenetic tree to confirm the subtype; in 2016, the same population was followed up, and the HIV subtype variation was analyzed, and the influencing factors of subtype variation were explored by multivariate logistic regression. Results:A total of 612 HIV/AIDS cases in 2014 and 2016 were collected. The age of the subjects was mainly 30 years old or above (85.46%, 523/612), and the proportion of people over 50 years old was higher (228/612, 37.25%). The main route of transmission was homosexuality, accounting for 49.67%. A total of 1224 samples were detected and CRF01 _ AE、CRF07_ BC、B、CRF08_ BC、CRF67_ 01B、CRF55_ 01B、CRF68_ 01B, 7 subtypes of HIV-1 and 5 unique recombinant types (URFs) was detected. CRF01_ AE and CRF07_ BC was still the main genotype in Wuxi, Jiangsu Province, accounting for 66.75%. There were 29 cases (3.56%) of URFs recombinant strains. During 2014-2016, the variation rate of subtypes was 14.63%, and the most common variation was CRF01_ AE changes to CRF07_ BC(13.95%). Marital status (OR=0.363, 95% CI: 0.137-0.964) and baseline CD4 level (OR=0.414, 95% CI: 0.192-0.891) were associated with subtype variation.Conclusions:The HIV-1 subtypes of HIV/AIDS patients in Wuxi city are diverse and complex, the proportion of recombinant subtypes is rising, the URFs that are difficult to determine the genotype increase significantly, and the variation rate of HIV-1 subtypes among HIV/AIDS infected people is high. It is necessary to strengthen the monitoring of HIV-1 subtypes.

OBJECTIVE: To investigate the correlation between the severity of obstructive sleep apnea syndrome (OSAS) and red cell distribution width (RDW) in elderly patients. METHODS: A cross-sectional study was conducted among 311 elderly patients diagnosed with OSAS in the snoring clinic between January, 2015 and October, 2016 and 120 healthy controls without OSAS from physical examination populations in the General Hospital of PLA. The subjects were divided into control group with apnea-hypopnea index (AHI) <5 (=120), mild OSAS group (AHI of 5.0-14.9; =90), moderate OSAS group (AHI of 15.0-29.9; =113) and severe OSAS group (AHI ≥ 30; =108). The clinical characteristics and the results of polysomnography, routine blood tests and biochemical tests of the subjects were collected. Multiple linear regression analysis was used to examine the correlation between OSAS severity and RDW. RESULTS: The levels of RDW and triglyceride were significantly higher in severe OSAS group than in the other groups ( < 0.01). The levels of fasting blood glucose and body mass index were significantly higher in severe and moderate OSAS groups than in mild OSAS group and control group ( < 0.05 or < 0.01). Multiple linear regression analysis showed that AHI was positively correlated with body mass index (β=0.111, =0.032) and RDW (β=0.106, =0.029). The area under ROC curve of RDW for predicting the severity of OSAS was 0.687 (=0.0001). CONCLUSIONS The RDW increases as OSAS worsens and may serve as a potential marker for evaluating the severity of OSAS.
Aged ; Cross-Sectional Studies ; Erythrocyte Indices ; Humans ; Polysomnography ; Severity of Illness Index ; Sleep Apnea, Obstructive

Objective The purpose of this research is to use modern statistical methods,to analyze the rules of cointment by Prof.Yang Zhimin treating yang deficiency and fatigue state patients,to increase the pertinence and to improve the clinical efficacy.Methods This paper analyzed 62 cases of Prof.Yang Zhimin in the treatment of the patients with yang deficiency and fatigue state from October 2010 to January 2013.The analyses were frequency analysis and association rules.Results Among the patients with yang-deficiency and fatigue,193 Chinese medicine were used.The monkshood was the highest frequency.Dampness-transforming medicine accounts for about 22.2％ in the top 36 frequency of medicine.Based on analyzing association rules,we found that the compatibility of medicine which were used more frequently came from Sini decoction,Danggui Sini decoction and Jinkui Shenqi pills,such as "monkshood and dried ginger","monkshood and roasted liquorice","dried ginger and roasted liquorice","monkshood and angelica","monkshood and comel","monkshood and prepared rehmannia root" and "monkshood and yam".Futhermore,we found two new core prescription.One was Qian Yang Dan combined with Sini decoction consist of "monkshood,roasted liquorice,dried ginger,fructus amomi".The other one was Tu Si Jian consist of "yam,semen cuscutae,angelica,roasted liquorice".Conclusions "Invigorating spleen and kidney","warming yang and dissipating dampness" and "hiding yang and Seeking Yang in Yin" are the habits and rules of the ointment medication by Prof.Yang Zhimin treatingyang deficiency and fatigue state patients.

Objective To investigate the expression changes of astrocytic syntrophin in hippocampus from human mesial temporal lobe epilepsy (MTLE). Methods From April, 2015 to July, 2016, 17 cases of hippocampus, collected from temporal lobectomy, were divided into MTLE group (n=13) and non-MTLE group (n=4) according to hematoxylin and eosin staining, glial fibrillary acidic protein and neuronal nu-clei immunohistochemical staining. Immunofluorescence double labeling and immunofluorescence histochemistry were used to observe the expression of syntrophin. Results The proliferation of astrocytes increased and neurons reduced in the hippocampus of MTLE group. Syntro-phin was found in the membrane and foot processes of astrocyte, that was enriched along perivascular astrocyte end-feet domain in non-MTLE group, but lost in MTLE group. While the whole expression of syntrophin was more in MTLE group than in non-MTLE group (t=5.421, P<0.001). Conclusion The distribution of syntrophin in hippocampus astrocytes may be related to the development of MTLE.