Objective: To examine the association between frailty and cognitive function in middle-aged and elderly populations using group-based trajectory model (GBTM), so as to provide insights into the prevention and intervention strategies for cognitive impairment in this population. Methods: From 2011 to 2018, data of demographic information and lifestyle behavior for individuals aged ≥45 years were collected from the China Health and Retirement Longitudinal Study. Frailty status was assessed using the frailty index, and cognitive function was evaluated using the Chinese version of the Mini-Mental State Examination. GBTM was applied to establish frailty trajectories based on the frailty index from 2011 to 2018 to analyze the trajectory of frailty changes. The association between frailty and cognitive function was analyzed using multiple linear regression model. Results: A total of 4 809 participants were included, with a mean age of (56.63±7.73) years. There were 2 621 males (54.50%) and 2 188 females (45.50%). The 2018 survey identified 574 individuals (11.94%) with cognitive function decline. GBTM identified four distinct frailty trajectories including the normal and stable group (69.27%), recovering frail group (9.32%), progressing pre-frail group (16.20%) and persistently frail group (5.22%). The mean cognitive funtion scores for these groups were (17.24±4.83) (16.38±5.53) (15.74±5.20) (15.02±5.11) points, respectively. The differences in cognitive funtion scores across groups were statistically significant (P<0.05). Multiple linear regression analysis showed, after adjusting for confounding factors such as gender, age, nighttime sleep duration, and smoking, compared with the normal and stable group, the cognitive function decline risk was higher in the frailty recovery group (β=-0.581), the pre-frail progression group (β=-0.583), and the persistently frail group (β=-0.662) compared with the non-frail stable group (all P<0.05). Conclusions There are four groups of changes in frailty among the middle-aged and elderly populations. Compared with the normal and stable group, the groups experiencing progression, persistence, and recovery of frailty exhibit a more pronounced risk of cognitive funtion decline.

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Objective To analyze the morphology of the pterygoid hamulus and its relationship with adjacent tissues on CBCT ima-ges,establish reference data of the anatomical structure of the pterygoid hamulus in the adult population,in order to provide a basis for clinical assisted diagnosis and treatment of pterygoid hamulus syndrome and obstructive sleep apnea hypopnea syndrome.Methods A total of 151 patients with CBCT images who met the inclusion criteria were collected from August 2020 to December 2023 in the Depart-ment of Stomatology at the Second Traditional Chinese Medicine Hospital of Jiangsu Province.The CBCT images were reconstructed u-sing the maximum intensity projection(MIP)and volume rendering(VR)modes of cone-beam CT.The morphology,length,width,vertical height,abduction angle,mucosal thickness,distance from the pterygoid hamulus to the midline of the palate,and distance from the pterygoid hamulus to the greater palatine foramen were observed and statistically analyzed in 302 bilateral cases.The differ-ences in the morphology of the pterygoid hamulus and its adjacent tissues were analyzed in different places,genders and age groups.Results The apex of the pterygoid hamulus faced inward on 6 sides and outward on 296 sides.The apex of the pterygoid hamulus was sharp on 46 sides and blunt on 256 sides.The pterygoid hamulus showed no statistically significant differences in various parameters be-tween the left and right sides,except for the width.In males,the length,width,height,distance from the pterygoid hamulus to the mid-palatal suture,and mucosal thickness on the surface of the hamulus were all greater than those in females,demonstrating statisti-cally significant differences.Females also exhibited a larger outward angle of the pterygoid hamulus than males,which was statistically significant.Moreover,with the increase of age,the length and height of the pterygoid hamulus initially increased and then decreased,exhibiting statistically significant differences.Conclusion CBCT has the advantages of low radiation dosage,convenient operation,clear imaging,stable measurement data,and clear images in the examination of pterygoid hamulus.It helps in the diagnosis and treat-ment of pterygoid hamulus-related diseases in a clinical setting.

BACKGROUND: Previous studies have examined the bulk transcriptome of peripheral blood immune cells in acquired immunodeficiency syndrome patients experiencing immunological non-responsiveness. This study aimed to investigate the characteristics of specific immune cell subtypes in acquired immunodeficiency syndrome patients who exhibit immunological non-responsiveness. METHODS: A single-cell transcriptome sequencing of peripheral blood mononuclear cells obtained from both immunological responders (IRs) (CD4 + T-cell count >500) and immunological non-responders (INRs) (CD4 + T-cell count <300) was conducted. The transcriptomic profiles were used to identify distinct cell subpopulations, marker genes, and differentially expressed genes aiming to uncover potential genetic factors associated with immunological non-responsiveness. RESULTS: Among the cellular subpopulations analyzed, the ratios of monocytes, CD16 + monocytes, and exhausted B cells demonstrated the most substantial differences between INRs and IRs, with fold changes of 39.79, 11.08, and 2.71, respectively. In contrast, the CD4 + T cell ratio was significantly decreased (0.39-fold change) in INRs compared with that in IRs. Similarly, the ratios of natural killer cells and terminal effector CD8 + T cells were also lower (0.37-fold and 0.27-fold, respectively) in the INRs group. In addition to several well-characterized immune cell-specific markers, we identified a set of 181 marker genes that were enriched in biological pathways associated with human immunodeficiency virus (HIV) replication. Notably, ISG15 , IFITM3 , PLSCR1 , HLA-DQB1 , CCL3L1 , and DDX5 , which have been demonstrated to influence HIV replication through their interaction with viral proteins, emerged as significant monocyte marker genes. Furthermore, the differentially expressed genes in natural killer cells were also enriched in biological pathways associated with HIV replication. CONCLUSIONS We generated an atlas of immune cell transcriptomes in HIV-infected IRs and INRs. Host genes associated with HIV replication were identified as markers of, and were found to be differentially expressed in, different types of immune cells.
Humans ; Acquired Immunodeficiency Syndrome ; Transcriptome/genetics* ; HIV ; HIV Infections/genetics* ; Leukocytes, Mononuclear/metabolism* ; CD4-Positive T-Lymphocytes/metabolism* ; Virus Replication ; Membrane Proteins/metabolism* ; RNA-Binding Proteins/metabolism*

Objective:To investigate the efficacy of tyrosine kinase inhibitors (TKI) in the treatment of metastatic renal cell carcinoma with rhabdoid differentiation(mRCC-R) or sarcomatoid differentiation(mRCC-S)and the survival of the patients.Methods:The clinicopathological and postoperative follow-up data of 5 patients with mRCC-R and 9 with mRCC-S confirmed by pathology from February 2016 to December 2018 in Tianjin Medical University Cancer Hospital were reviewed. There were 3 male and 2 female patients in mRCC-R group, with the average age of (60.2±7.1)years old. The clinic manifestation included back or abdominal pain in 2 cases, loss of appetite and weight in one case and founding during physical examination in 2 cases, with the average maximum diameter was (8.8±4.1)cm. The site of tumor included left kidney in 3 cases and right kidney in 2 cases. Lung metastasis was found in 4 cases. Lung and peritoneum metastasis was found in one case. There were 8 male and 1 female patients in mRCC-S group, with the average age of (58.0±8.0)years old. The clinic manifestation included back or abdominal pain in one case, loss of weight in one case, gross hematuria in one case and founding during physical examination in 6 cases. The average diameter of tumor was (8.9±3.5)cm. The site of tumor included left kidney in 4 cases and right kidney in 5 cases. Postoperative metastasis included lung in 3 cases, bone in one case, retroperitoneal lymph node in one case, brain in one case, lung associated with bone in one case. All of the patients were pathologically diagnosed with renal clear cell carcinoma. After metastasis, 5 cases of mRCC-R and 6 cases of mRCC-S were treated with Sorafenib, 2 cases of mRCC-S were treated with Sunitinib, and 1 case of mRCC-S was treated with Axitinib. The efficacy of TKI for the two specific pathological types and for single pathological type at the early postoperative period (within 3 months) and 3 months later was compared. Meanwhile, subgroup analysis was performed on the efficacy of TKI and survival of patients with same metastatic sites in the two groups.Results:The mean overall survival(OS) of mRCC-R and mRCC-S treated with TKI was (26.5±5.5)months and (20.7±4.7) months( P=0.329), and the mean progression-free survival (PFS) was (21.9±5.5) months and (6.3±2.1)months( P=0.013), respectively. Comparing the efficacy of using TKI in the early postoperative period and after 3 months, the mean OS was (27.5±6.5)months and (16.8±6.1)months ( P=0.619), and the mean PFS was (12.3±3.3)months and (3.3±1.7)months ( P=0.096), respectively. There was only 1 patient with mRCC-R who used TKI within 3 months after surgery, and the result was disease progressed and eventually died, OS was 3 months. Comparing the efficacy of TKI in mRCC-R and mRCC-S with lung metastasis alone, the mean OS was (33.3±2.2) months and (19.5±8.9)months ( P=0.118), and the mean PFS was (27.3±3.1) months and (7.8±4.2) months ( P=0.009), respectively. Patients with liver, bone or brain metastasis only occurred in mRCC-S, so it is unable to identify the efficacy of TKI in the two groups. Conclusions:The efficacy of TKI in the treatment of mRCC-R was better than mRCC-S, and there was statistically significant difference in PFS, especially in patients with lung metastasis alone in the two groups. There was no significant difference in the efficacy between patients with mRCC-R who took TKI in the early postoperative period (within 3 months)and those who took TKI after 3 months.

OBJECTIVE: To determine the types and frequency of deafness-related variants among 7875 newborns from Dongying area of Shandong Province. METHODS: One hundred loci of 18 common deafness genes were subjected to semiconductor sequencing. Variant site, frequency and distribution of the variants were analyzed. RESULTS: In total 552 deafness gene variants were detected among the 7875 newborns, which yielded a detection rate of 7.01%. Among these, common variant sites for GJB2, SLC26A4 and GJB3 genes were c.235delC, IVS7-2A>G and c.538C>T, respectively. The variant frequencies of matrilinear inheritance deafness genes MT-CO1, MT-RNR1, MT-TL1 and MT-TS1 were 0.38%, 0.25%, 0.1% and 0.01%, respectively. Four newborns were diagnosed with deafness, among which one had unilateral hearing loss. Analysis of the proportions of neonatal deafness-related variants in five counties of Dongying showed that the highest variant rate for the SLC26A4 gene compared with GJB2 was in Lijin county (51.76% vs. 40%), while the lowest was in Hekou county (30.77% vs. 56.41%). CONCLUSION The carrier rate of deafness-related variants in Dongying area is higher than other regions of China, which may be attributed to the increased types and variant sites covered by the semiconductor sequencing method compared with the chip method and time-of-flight mass spectrometry. Due to geographical and population aggregation factors, the proportion of deafness variants in the five counties of Dongying differed significantly. Above results may provide a guide for the prevention of congenital deafness in Dongying area.

Due to the influence of immunosuppression, nerve injury and other comprehensive factors, the overall incidence of gastrointestinal complications after lung transplantation is relatively high, which can cause drug absorption disorder and chronic rejection. In recent years, more and more studies have been conducted on these complications. However, due to the great difference of the incidence of gastrointestinal complications among lung transplantation centers, clinicians lack of understanding of these. In this article, the general status, common types and risk factors of gastrointestinal complications after lung transplantation were reviewed, aiming to provide reference for comprehensive management of gastrointestinal complications after lung transplantation.

Objective To investigate the mechanism of EMT and invasion promoted by miR-21 in prostate cancer cells. Methods The sequence of miR-21 mimic/inhibitor was firstly designed and synthesized. Then miR-21 mimic/inhibitor and its control were transfected into prostate cancer cells C4-2 and DU145, respectively. And cells were collected for mRNA isolation and RT-qPCR analysis for miR-21 and FOXOl. FOXOl, E-cadherin and N-cadherin were detected by Western blot, and the invasion of prostate cancer cells were detected by transwell assays. Results The expression of miR-21 increased in both C4-2 and DU145 after transfection, and the expression of FOXOl mRNA increased at the same time (P＜0.01).The expression of miR-21 and FOXOl mRNA in C4-2 and DU145 was decreased by miR-21 inhibitor(P＜ 0.05). The protein expression of FOXOl and N-cadherin in C4-2 and DU145 increased after the treatment of miR-21, while that of E-cadherin decreased. The protein expression of FOXOl and N-cad-herin in C4-2 and DU145 decreased after the treatment of miR-21 inhibitor, while that of E-cadherin increased. The invasive level in C4-2 and DU145 increased after the treatment of miR-21, while that decreased after the treatment of miR-21 inhibitor. Conclusion MiR-21 promotes EMT and invasion by inducing FOXOl in prostate cancer cells.

Objective To assess the effect of ascorbic acid/ferric chloride (AA/FeCl3) in attenuating cartilage damage in rats with osteoarthritis. Methods Thirty adult male Wistar rats with surgically induced osteoarthritis were randomized into 2 groups for treatment with intra-articular injection of saline (control group) or AA/FeCl3 mixture (AA group) once a week starting from the third week after the operation. At 6, 9, and 12 weeks after the operation, 5 rats from each group were sacrificed for observing subchondral bone changes on X-ray films and evaluation of cartilage degeneration in the right knee joints using safranin-O/Fast green staining and a modified OARSI scoring system. The degradation of the cartilage matrix was observed by immunohistochemical staining for type II collagen. Results X-ray examination in saline control group revealed the presence of osteophytes and narrowing of the joint space at 9 weeks, and the joint line disappeared at 12 weeks after the surgery; only slight irregularity of the articular surface was observed in the AA group at 9 and 12 weeks. OARSI scores were significantly lower in AA group than in the control group at 9 weeks (18.67 ± 0.67 vs 12.17 ± 2.75;P<0.05) and 12 weeks (20.11 ± 1.84 vs 13.77 ± 0.40;P<0.05) but not at 6 weeks after the surgery. The content of type 2 collagen in AA group was significantly higher than that in the control group at 6 weeks (0.36 ± 0.039 vs 0.49 ± 0.029;P<0.05) and 9 weeks after the surgery (0.25 ± 0.041 vs 0.38 ± 0.040;P<0.05). Conclusions Early intra-articular injection of AA/FeCl3 can effectively delay the progression of post-traumatic osteoarthritis in rats.

Objective To assess the effect of ascorbic acid/ferric chloride (AA/FeCl3) in attenuating cartilage damage in rats with osteoarthritis. Methods Thirty adult male Wistar rats with surgically induced osteoarthritis were randomized into 2 groups for treatment with intra-articular injection of saline (control group) or AA/FeCl3 mixture (AA group) once a week starting from the third week after the operation. At 6, 9, and 12 weeks after the operation, 5 rats from each group were sacrificed for observing subchondral bone changes on X-ray films and evaluation of cartilage degeneration in the right knee joints using safranin-O/Fast green staining and a modified OARSI scoring system. The degradation of the cartilage matrix was observed by immunohistochemical staining for type II collagen. Results X-ray examination in saline control group revealed the presence of osteophytes and narrowing of the joint space at 9 weeks, and the joint line disappeared at 12 weeks after the surgery; only slight irregularity of the articular surface was observed in the AA group at 9 and 12 weeks. OARSI scores were significantly lower in AA group than in the control group at 9 weeks (18.67 ± 0.67 vs 12.17 ± 2.75;P<0.05) and 12 weeks (20.11 ± 1.84 vs 13.77 ± 0.40;P<0.05) but not at 6 weeks after the surgery. The content of type 2 collagen in AA group was significantly higher than that in the control group at 6 weeks (0.36 ± 0.039 vs 0.49 ± 0.029;P<0.05) and 9 weeks after the surgery (0.25 ± 0.041 vs 0.38 ± 0.040;P<0.05). Conclusions Early intra-articular injection of AA/FeCl3 can effectively delay the progression of post-traumatic osteoarthritis in rats.