Objective To construct a prediction model for the population with hypertension and diabetes to assess the risk of chronic kidney disease (CKD), and to provide a scientific basis for formulating targeted CKD prevention and control measures. Methods Based on physical examination data from community residents aged 60 years and above in Nanjing in 2022, 10 221 patients with hypertension and diabetes were selected as the study subjects. Variables associated with CKD prevalence were screened using univariate analysis, and further variable selection was performed using LASSO regression. Finally, a CKD risk prediction model was constructed based on logistic regression. The model's performance was evaluated using the ROC curve and calibration curve. Results The prevalence rate of CKD in the study population was 22.71%, with a mean age of 71.66 years. LASSO regression identified seven variables associated with CKD: age, blood urea nitrogen (BUN), hemoglobin, uric acid, triglyceride-glucose (TyG) index, urine protein-to-creatinine ratio (UPCR), and medical insurance type. The final logistic regression model incorporated six variables: age [OR=1.067 (95% CI: 1.058-1.076)], BUN [OR=1.377 (95% CI: 1.338-1.418)], hemoglobin [OR=0.992 (95% CI: 0.989-0.995)], uric acid [OR=1.004 (95% CI: 1.003-1.004)], TyG index [OR=1.445 (95% CI: 1.324-1.577)], and self-payment medical insurance [OR=1.732 (95% CI: 1.542-1.945)]. The model had an AUC of 0.759 (95% CI: 0.747-0.770) and a Brier score of 0.140 (95% CI: 0.136-0.145), indicating good predictive performance. The calibration curve showed good agreement between the predicted risk and the observed value. Conclusion The constructed LASSO-logistic regression risk prediction model in this study can effectively assess the risk of CKD in elderly individuals aged 60 years and above with hypertension and diabetes, providing a basis for early identification of high-risk individuals and the formulation of targeted CKD prevention and control measures.

ObjectiveTo explore the mechanism by which the Shenfu Xiongze prescription regulates autophagy in rats with myocardial remodeling through the adenosine monophosphate-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） signaling pathway. MethodsA rat model of myocardial remodeling induced by isoprenaline （ISO） was established. Rats were divided into the blank group，the model group，the low-，medium-， and high-dose groups of Shenfu Xiongze prescription，and the captopril group， 6 rats in each group. Except for the blank group，the rat model of myocardial remodeling was established in the other groups by intraperitoneal injection of 2.5 mg·kg^-1 ISO for 3 consecutive weeks. At the same time of modeling， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription were administered the corresponding doses of Shenfu Xiongze prescription solution （8.4，16.8，and 33.6 g·kg^-1），and the captopril group was administered captopril solution （25 mg·kg^-1）. As for the blank group and the model group， the same volume of normal saline was given. The treatment was continued for 3 weeks. Echocardiography was used to observe the cardiac structure and function，and the heart weight index was detected. Masson staining and hematoxylin-eosin （HE） staining were used to observe the pathological morphology changes of myocardial tissue. The levels of interleukin-6 （IL-6） and B-type natriuretic peptide （BNP） in serum were detected by enzyme-linked immunosorbent assay （ELISA）. The expression of type Ⅰ collagen （Collagen Ⅰ），type Ⅲ collagen （Collagen Ⅲ），and microtubule-associated protein 1 light chain 3 （LC3） proteins in myocardial tissue was determined by immunohistochemistry. Autophagy was observed by transmission electron microscopy. The mRNA expression of Collagen Ⅰ，Collagen Ⅲ，α-smooth muscle actin （α-SMA），LC3，yeast Atg6 homolog protein （Beclin-1），AMPK，and mTOR in myocardial tissue was detected by quantitative real-time polymerase chain reaction （real-time PCR）. The protein expression of Collagen Ⅰ，α-SMA，transforming growth factor-β₁ （TGF-β₁），LC3，Beclin-1，p62， phosphorylation（p）-AMPK，p-mTOR，AMPK，and mTOR was detected by Western blot. ResultsCompared with the normal group，rats in the model group exhibited significantly decreased values of ejection fraction （EF） and left ventricular fractional shortening （FS） （P<0.01）， significantly increased values of left ventricular end-diastolic diameter （LVIDd） and left ventricular end-systolic diameter （LVIDs） （P<0.01）. Additionally， the model group also showed increased degrees of inflammatory infiltration and fibrosis of myocardial tissue， significantly elevated levels of serum IL-6 and BNP （P<0.01）， significantly increased mRNA and protein levels of Collagen Ⅰ，Collagen Ⅲ，α-SMA，and mTOR （P<0.01），and markedly decreased mRNA and protein levels of LC3，Beclin-1，and AMPK （P<0.05，P<0.01）. Compared with the model group， the low-，medium-， and high-dose groups of Shenfu Xiongze prescription presented significantly elevated EF and FS values （P<0.01） and lowered LVIDd and LVIDs （P<0.05）. In these groups， the inflammation and fibrosis were alleviated significantly. They also exhibited decreased serum levels of IL-6 and BNP （P<0.01）， significantly reduced protein expression of Collagen Ⅰ， α-SMA， TGF-β₁， p62， and p-mTOR （P<0.01）， significantly decreased mRNA expression of Collagen Ⅰ， Collagen Ⅲ， α-SMA， and mTOR （P<0.01）， and significantly increased mRNA and protein levels of LC3， Beclin-1， and AMPK （P<0.05，P<0.01）. ConclusionThe Shenfu Xiongze prescription can improve the myocardial remodeling induced by ISO in rats by regulating the autophagy level，enhance cardiac function，and reduce inflammatory and fibrotic levels. This effect may be achieved through the AMPK/mTOR signaling pathway.

Objective:To compare pregnancy outcomes between patients undergoing combined hysteroscopy and hysterosalpingo-contrast sonography (HyCoSy) versus hysteroscopy alone prior to intrauterine insemination, and to evaluate the safety and clinical value of the combined procedure in the diagnosis and treatment of infertility.Methods:A retrospective analysis was conducted on clinical data from 385 patients who underwent hysteroscopy at Peking University Third Hospital between October 1, 2020 and September 30, 2022, and subsequently received their first cycle of artificial insemination with donor sperm (AID) within six months. Pregnancy outcomes were compared between the group receiving combined hysteroscopy with four-dimensional HyCoSy (hysteroscopy+4D-HyCoSy group) and the group receiving hysteroscopy alone (hysteroscopy group). Multivariate logistic regression was used to analyze factors influencing pregnancy outcomes after AID.Results:Among the 385 patients included, 79 achieved clinical pregnancy. The clinical pregnancy rate (24.9%, 53/213) and live birth rate (21.1%, 45/213) in the hysteroscopy+4D-HyCoSy group were significantly higher than those in the hysteroscopy group [15.1% (26/172) and 12.8% (22/172), respectively; all P<0.05]. There was no significant difference in tubal patency between the two groups ( P>0.05); however, the time interval from tubal patency assessment to intrauterine insemination was significantly longer in the hysteroscopy group compared to the hysteroscopy+4D-HyCoSy group (median: 4.0 vs 2.0 months; P<0.001). Multivariate analysis showed that double insemination significantly increased clinical pregnancy rate compared to single insemination ( OR=2.42, 95% CI: 1.02-5.72; P=0.044). An interval exceeding 6 months between tubal patency assessment and intrauterine insemination was identified as a risk factor for reduced clinical pregnancy ( OR=0.35, 95% CI: 0.14-0.92; P=0.047). Additionally, neither the time interval from hysteroscopy to intrauterine insemination nor hysteroscopic findings and pathological diagnoses had significant effects on clinical pregnancy rates (all P>0.05). Conclusions:The combination of hysteroscopy and HyCoSy provides a safe and efficient approach for fertility assessment in infertile patients and improves clinical pregnancy rate and live birth rate in intrauterine insemination cycles. Hysteroscopy is recommended for patients with suspected endometrial or intrauterine abnormalities. If no previous tubal patency assessment has been performed or the last assessment was more than six months prior, combined hysteroscopy and HyCoSy may be considered to enhance the likelihood of clinical pregnancy.

Objective:To investigate the clinical manifestations, pathological features, and genetic variant characteristics of children with glycogen storage disease type Ⅸa (GSD Ⅸa).Methods:A retrospective case series analysis was conducted to collected and analyzed the medical history, biochemical markers, liver ultrasound results, liver histopathological findings, genotypes, treatment regimens, and follow-up data of 4 pediatric patients diagnosed with GSD IXa in the Department of Infectious Diseases at Xiamen Children′s Hospital from January 2018 to May 2024. All patients were confirmed by genetic testing.Results:All 4 pediatric patients diagnosed with GSD Ⅸa were male. The ages of onset were 8 months, 2 years, 3 years and 3 months, 1 year and 5 months, respectively, with initial presentations including chronic diarrhea (Case 1), incidentally detected transaminase elevation during routine examinations (Cases 2 and 3), and delayed motor development (Case 4). Diagnosis was confirmed at ages 10 months, 3 years, 3 years 4 months and 1 year 6 months, respectively.At diagnosis, anthropometric parameters and biochemical profiles revealed:Height: 68 cm (< P3), 96 cm ( P25-50), 94 cm ( P3-10), and 94 cm ( P3-10).Weight: 7 kg (< P3), 17 kg ( P90-97), 14.4 kg ( P25-50), and 10.5 kg ( P25-50).Alanine aminotransferase: 299, 500, 271, and 313 U/L (reference range 0-40 U/L).Aspartate aminotransferase: 285, 543, 337 and 357 U/L (reference range 0-40 U/L).Fasting glucose: 2.80, 3.67, 2.98, and 3.66 mmol/L (reference range 3.90-6.10 mmol/L).Lactate: 4.3, 2.1, 1.3, and 2.6 mmol/L (reference range 0.5-2.2 mmol/L).Triglycerides: 5.22, 1.38, 1.32, and 1.88 mmol/L (reference range 0.56-1.70 mmol/L).Case 1 exhibited poor adherence to uncooked cornstarch therapy during initial treatment, with no significant improvement in biochemical parameters. Follow-up imaging at age 4 revealed hepatic adenoma. Subsequent improvement in therapeutic compliance led to biochemical normalization, reduced hepatic adenoma size, and growth parameters of 113 cm ( P10-25) and 26 kg ( P90-97) at 6 years 2 months. Cases 2-4 demonstrated biochemical improvement with regular uncooked cornstarch therapy and no evidence of hepatic adenoma.Liver histopathology in Cases 1-3 confirmed glycogen accumulation consistent with GSD, without cirrhotic changes. Genetic analysis identified PHKA2 variations in all cases: 2 missense variants, 1 frameshift variant and 1 nonsense variant. The c.2839dup and c.3267G>A variants represent novel pathogenic mutations. Conclusions:GSD Ⅸa in pediatric patients is predominantly characterized by hepatomegaly, hepatic dysfunction, and hypoglycemia. While uncooked cornstarch therapy typically yields favorable prognoses, a subset of patients may develop hepatic adenomas. Notably, children with hepatic adenoma exhibited younger age of onset, significant growth retardation, and more severe metabolic disturbances, suggesting that hepatic adenoma development may be closely linked to the severity of metabolic dysregulation.

Objective:To evaluate the efficacy and safety of baricitinib combined with ruxolitinib cream in the treatment of progressive nonsegmental vitiligo.Methods:Clinical data were retrospectively collected from patients with progressive nonsegmental vitiligo in Boao Super Hospital. All the patients were treated with oral baricitinib daily (2 mg/day for patients weighing ≤ 50 kg; 4 mg/day for those > 50 kg) in combination with topical application of ruxolitinib cream twice daily for 24 consecutive weeks. Disease severity was assessed using the facial vitiligo area scoring index (F-VASI) and total body VASI (T-VASI) at baseline, week 12, and week 24. Adverse reactions were monitored throughout the treatment course.Results:Six patients with progressive nonsegmental vitiligo were collected, including 3 males and 3 females, aged 26 - 42 years, with the disease duration ranging from 0.5 to 25 years. At week 12, 3 patients achieved a 50% ~ < 75% improvement in facial vitiligo lesions (F-VASI 50), 1 patient achieved F-VASI 75 (75% ~ < 90% improvement), and 1 patient achieved T-VASI 50; at week 24, 4 patients achieved F-VASI 50, 1 patient achieved F-VASI 75, 1 patient achieved F-VASI 90 (≥ 90% improvement), and 3 patients achieved T-VASI 50. During the treatment, upper respiratory infection occurred in 1 patient, acne in 1 patient, pruritus in 2 patients, elevation of total cholesterol levels in 2 patients, and increase of high-density lipoprotein levels in 2 patients. No severe adverse events were observed during the treatment.Conclusion:The combination therapy with baricitinib and ruxolitinib cream may have potential efficacy and safety in the treatment of progressive nonsegmental vitiligo.

Objective:To investigate the numbers of peripheral blood CD4 +T cell subpopulations in patients with elderly-onset rheumatoid arthritis (EORA) and its clinical significance. Methods:A total of 188 patients with newly diagnosed RA in the department of rheumatology and immunology of the Second Hospital of Shanxi Medical University from January 2020 to December 2023 were collected, including 48 cases of EORA (age of onset: ≥60 years old), 140 cases of young-onset rheumatoid arthritis (YORA) (18 years old ≤ age of onset < 60 years old). Meanwhile, 151 healthy controls (HC) were collected, of which 31 persons aged 60-85 years were included as HC group 1 (HC 1) and 120 individuals aged 18-59 years were included as HC group 2 (HC 2). Peripheral blood CD4 +T lymphocyte subsets of these participants were assessed by flow cytometry. Differences between groups were analyzed using independent-samples t test, Mann-Whitney U test or χ2 test. Results:Compared with healthy individuals, the absolute counts and percentages of peripheral blood Treg cells in patients with EORA were significantly decreased [absolute counts: 32.65 (23.04, 47.73) cells/μl vs. 23.03 (15.28, 32.12) cells/μl, Z=-3.35, P=0.001; percentages: 5.12%(4.13%, 6.16%) vs. 3.72% (2.79%, 4.82%), Z=-4.10, P<0.001], while the Th17/Treg cell ratio was increased [0.16 (0.12, 0.29) vs. 0.26 (0.18, 0.46), Z=-2.94, P=0.003], the differences are all significant. There was a tendency with higher absolute counts and percentages of Treg [absolute counts: 23.03 (15.28, 32.12) cells/μl vs. 20.97 (14.01, 30.64) cells/μl, Z=-0.58, P=0.561; percentages: 3.72%(2.79%, 4.82%) vs. 3.38% (2.39%, 4.71%), Z=-1.06, P=0.287] and lower Th17/Treg ratios [0.26 (0.18, 0.46) vs. 0.27 (0.19, 0.46), Z=-0.32, P=0.751] in EORA when compared to patients with YORA, but no significant differences were observed. Conclusion:Patients with EORA also have the reduced numbers of peripheral blood Treg cells and immune imbalance of Th17/Treg, suggesting that immune imbalance or dysfunction caused by defects in Treg cell counts and/or function contributes to the development of EORA, and that targeting Treg cells may be a promising therapeutic strategy for EORA.

Gut microbial communities are likely remodeled in tandem with accumulated physiological decline during aging, yet there is limited understanding of gut microbiome variation in advanced age. Here, we performed a metagenomics-based enterotype analysis in a geographically homogeneous cohort of 367 enrolled Chinese individuals between the ages of 60 and 94 years, with the goal of characterizing the gut microbiome of elderly individuals and identifying factors linked to enterotype variations. In addition to two adult-like enterotypes dominated by Bacteroides (ET-Bacteroides) and Prevotella (ET-Prevotella), we identified a novel enterotype dominated by Escherichia (ET-Escherichia), whose prevalence increased in advanced age. Our data demonstrated that age explained more of the variance in the gut microbiome than previously identified factors such as type 2 diabetes mellitus (T2DM) or diet. We characterized the distinct taxonomic and functional profiles of ET-Escherichia, and found the strongest cohesion and highest robustness of the microbial co-occurrence network in this enterotype, as well as the lowest species diversity. In addition, we carried out a series of correlation analyses and co-abundance network analyses, which showed that several factors were likely linked to the overabundance of Escherichia members, including advanced age, vegetable intake, and fruit intake. Overall, our data revealed an enterotype variation characterized by Escherichia enrichment in the elderly population. Considering the different age distribution of each enterotype, these findings provide new insights into the changes that occur in the gut microbiome with age and highlight the importance of microbiome-based stratification of elderly individuals.
Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; Bacteroides ; China ; Diabetes Mellitus, Type 2/microbiology* ; Escherichia coli/classification* ; Gastrointestinal Microbiome/genetics* ; Metagenomics ; East Asian People

OBJECTIVE: To explore the effect of light music therapy on delirium in intensive care unit (ICU) patients undergoing invasive mechanical ventilation, and provide evidence-based support for clinical prevention of delirium. METHODS: A prospective randomized controlled trial was conducted. 140 patients with invasive mechanical ventilation admitted to the department of respiratory and critical care medicine of First Affiliated Hospital of Guangxi Medical University from January 2024 to January 2025 were enrolled. The patients were divided into intervention group and control group using a random number table method. The control group received routine treatment and nursing care, while the intervention group received light music therapy three times a day for 30 minutes each time for 7 consecutive days. The confusion assessment method-ICU (CAM-ICU) was used to evaluate delirium, and the incidence of delirium within 7 days was statistically analyzed. Richmond agitation-sedation score (RASS), critical care pain observation tool (CPOT) score, mechanical ventilation duration, the length of ICU stay, and ICU stay expenses were record. RESULTS: 129 cases were ultimately included, including 64 cases in the control group and 65 cases in the intervention group. There was no statistically significant difference in baseline data between the two groups, indicating comparability. The incidence of delirium in the intervention group was significantly lower than that in the control group (27.7% vs. 51.6%, χ ² = 7.687, P = 0.006). There was no significantly difference in RASS score between the two groups before enrollment (P = 0.840). After intervention, the RASS score in the intervention group significantly decreased, from 2.00 points on the 1st day of enrollment to 0.00 points on the 7th day, while the control group only decreased from 2.00 points to 1.50 points. The decreasing trend of the intervention group was more pronounced, especially on the 3rd day (P = 0.047) and the 7th day (P =0.005), with significant differences between the groups. The time effect (F = 18.929, P < 0.001), group effect (F = 6.655, P = 0.011), and time group interaction effect (F = 7.372, P < 0.001) of the two groups of RASS score were significant, suggesting that light music therapy has better timeliness and sustainability in improving patients' sedation status. There was no significantly difference in CPOT score between the two groups before enrollment (P = 0.902). After intervention, the CPOT score in the intervention group rapidly decreased from 3.00 points before enrollment to 1.00 points on the 1st day, and continued until the 7th day, while the control group showed a slower decrease from 2.50 points to 2.00 points and only dropped to 1.00 points on the 7th day. There were significant differences on 1st day and 3rd day between two groups (both P < 0.05). The time effect (F = 28.125, P < 0.001), group effect (F = 11.580, P = 0.001), and time group interaction effect (F = 4.048, P = 0.020) of the two groups of CPOT score were significant, indicating that light music therapy has better pain control, but the interaction effect is low, indicating that the impact of the intervention on the CPOT score was mainly concentrated in the early stage (1-3 days), and the long-term effect may be influenced by other factors. Compared with the control group, the intervention group showed a significant reduction in mechanical ventilation time (days: 10.57±2.94 vs. 11.95±3.74, P = 0.021) and the length of ICU stay (days: 14.91±4.37 vs. 17.53±4.83, P = 0.002). The ICU hospitalization expenses of the intervention group was slightly lower than that of the control group [ten thousand yuan: 22.431 (12.473, 28.489) vs. 29.362 (11.996, 41.389)], but the difference was not statistically significant (P = 0.086). CONCLUSIONS Light music therapy can effectively reduce the incidence of delirium in patients undergoing invasive mechanical ventilation, improve consciousness and pain perception, shorten mechanical ventilation time and hospital stay, and has significant clinical promotion value high-quality studies.
Humans ; Delirium/prevention & control* ; Intensive Care Units ; Respiration, Artificial ; Music Therapy ; Prospective Studies ; Male ; Female ; Middle Aged ; Critical Care ; Aged

Objective: To investigate the mechanism by which icariin ( ICA) inhibits the invasion and metastasis of human triple-negative breast cancer ( TNBC) cells via downregulation of the transforming growth factor-β/ Smad ( TGF-β/ Smad) signaling pathway． Methods: TNBC cells ( MDA-MB-231 and MDA-MB-468) were cultured in vitro and divided into four groups: an experimental group treated with 15 μmol / L ICA; a model group treated with 10 μmol / L TGF-β receptor inhibitor LY2109761; a combination group ( LY2109761 + ICA) treated with both 15 μmol / L ICA and 10 μmol / L LY2109761; and a control group．Cell proliferation，migration，and invasion were as- sessed using CCK-8，colony formation，5-ethynyl-2 '-deoxyuridine ( EdU) ，wound healing，and Transwell assays． The expression levels of epithelial-mesenchymal transition ( EMT) -related proteins，as well as TGF-β1，Smad2， and phosphorylated Smad2 ( P-Smad2) were detected by immunofluorescence and Western blot． Results: CCK-8 results showed that cell proliferation decreased gradually with increasing concentrations of ICA ( P＜0. 05) ．Colony formation and EdU assays indicated significantly inhibited proliferation in the ICA-treated group compared to the control ( P＜0. 05) ．Wound healing and Transwell assays demonstrated reduced migration and invasion capabilities in the experimental group relative to the control ( P＜0. 05) ．Compared to the model group，the LY2109761 + ICA group exhibited further suppression of invasion ( P＜0. 05) ．Immunofluorescence revealed decreased Vimentin ex- pression in the experimental group ( P＜0. 05) ，with an even more pronounced reduction in the LY2109761 + ICA group ( P＜0. 01) ．Western blot analysis showed that the protein levels of N-cadherin，matrix metalloproteinase-9( MMP9) ，Vimentin，TGF-β1，Smad2，and P-Smad2 were downregulated in the experimental group compared to the control ( P＜0. 05) ．These proteins were further suppressed in the LY2109761 + ICA group compared to the model group ( P＜0. 05) ． Conclusion ICA inhibits TNBC cells proliferation，invasion，metastasis，and EMT by downregulating the TGF-β/ Smad signaling pathway．

Objective To describe and evaluate the clinical studies of postoperative pain sensitization caused by sleep deprivation through the evidence map system,understand the distribution of evidence in this field,and provide reference for subsequent evidence research.Methods A computer-based search of PubMed,EMBASE,Cochrane library,Web of Science,CNKI,Wanfang Data,VIP and Chinese Biomedical Literature Database from inception to August 2023 was conducted to obtain intervent ion studies,observational studies and systematic reviews/Meta-analysis of postoperative pain sensitization caused by sleep deprivation.The research characteristics and methodological quality were analyzed and evaluated.The Cochrane Handbook for Systematic Reviews,the Newcastle-Ottawa Scale(NOS)and the AMSTAR-2 scale were used to evaluate the quality of the included studies,and the evidence was comprehensively analyzed and displayed by means of bubble chart,table and text.Results A total of 35 observational studies(31 cohort studies and 4 case-control studies),15 randomized controlled trials and 4 systematic reviews/Meta-analyses were included.The number of publications increased rapidly after 2018 and peaked in 2022,and clinical studies in this field mainly fo-cused on cohort studies,with fewer randomized controlled trials and systematic reviews/Meta-analysis studies.The results of the evidence map showed that in terms of quality,22 studies were'high quality',24 studies were'medium quality',and 8 studies were'low quality'.Thirty studies showed that sleep deprivation could induce postoperative pain sensitization.Only 2 studies suggested that sleep disorders were not significantly asso-ciated with postoperative pain sensitization,and ten studies were uncertain whether sleep deprivation could in-duce postoperative pain sensitization.Conclusions Overall evidence shows that sleep deprivation can induce postoperative pain sensitization,but the evaluation dimensions are limited and the methodological quality of the included literature needs to be improved.More high-quality,large-sample and standardized clinical studies should be carried out in the future to provide better scientific basis for clinical work.