Mainly based on the "constitution-syndrome-disease location correlation" approach， this study constructs a traditional Chinese medicine （TCM） framework for understanding hypertension comorbidities. From the perspective of shared constitutional predispositions and similar pathomechanistic characteristics， hypertension comorbidity should not be regarded as a simple aggregation of multiple diseases. Rather， it is generally rooted in biased constitutions such as yin-deficiency， qi-deficiency， yang-deficiency， phlegm-dampness， dampness-heat， and blood-stasis constitutions， accompanied by the long-term interplay of pathogenic mechanisms involving wind， fire， phlegm， stasis， and deficiency， and gradually manifests as comorbidities affecting different systems through the evolution of disease locations related to the liver， heart， spleen， and kidney. On this basis， cardiac-， cerebral-， renal-， and metabolic-related comorbidities are taken as the major categories， and their characteristics related to constitution， syndrome， and disease location are systematically summarized to clarify the correspondence between shared pathomechanisms and predominant disease locations， and to propose corresponding prevention and treatment strategies. This framework further incorporates constitution-based stratification into risk stratification for prospective intervention， and takes syndrome as the central link in developing multi-disease treatment strategies such as boosting qi and activating blood， as well as resolving phlegm and unblocking collaterals. A clinical pathway is thereby proposed， encompassing constitution assessment， syndrome differentiation， comorbidity risk stratification， integrated traditional Chinese and western medicine intervention， and follow-up feedback. This study aims to provide a reference for the theoretical development and collaborative management of hypertension comorbidities in TCM.

Objective:To explore the early clinical effect of arthroplasty with rotating hinge knee prosthesis in the treatment of severe knee deformity.Methods:A retrospective study was conducted on 55 patients who underwent primary rotating hinge knee arthroplasty at Shanghai Sixth People's Hospital from January 2017 to October 2023, including 19 male patients and 36 female patients, with an average age of 60.9±9.0 years (ranging from 31 to 74 years). The four main indications were end-stage deformity of osteoarthritis (valgus/varus>20°, 16 cases), post-traumatic joint deformity (15 cases), severe joint ligament instability (12 cases), and neuromuscular or immune diseases (12 cases). The patients were divided into two age groups: ≥60 years old group (32 cases) and <60 years old group (23 cases). Various pre-operative and post-operative data, including knee society score (KSS), range of motion (ROM), forgotten joint score (FJS), degree of force line offset and post-operative complications, were collected and compared.Results:All the 55 cases successfully underwent the operation. The operation time was 102.3±15.8 min. The intraoperative blood loss was 63±23.7 ml. The follow-up time was 37.2±7.9 months. KSS clinical score increased from 27.5(12, 45) before surgery to 90.5(85, 95) after surgery ( P<0.001) and the mean score of KSS function increased from 50.4(45, 60) before surgery to 84.3(85, 95) after surgery ( P<0.001), both with significant difference ( P<0.05). Similarly, the average postoperative ROM improved from 97.2°±34.4° to 120.1°±10.9°with significant difference ( P<0.05). The postoperative FJS was 81.0±6.6. Up to the last follow-up, the implant survival rate was 98%[95% CI(90.4%, 99.6%)]. For the all four groups of end-stage deformity of osteoarthritis, post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases, both the KSS score and the ROM of the knee joint were significantly improved. There was no significant difference in neither the KSS score or the ROM of the knee joint between the ≥60 years old group and the <60 years old group ( P>0.05). The incidence of complications was 24% (13/55). The complication rates for patients with end-stage deformity of osteoarthritis, post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases were 12.5% (2/16), 20% (3/15), 25% (3/12), and 41.7% (5/12) respectively, without significant difference. The incidence of complications in elderly patients (85%, 11/13) was much higher than that in younger patients (5%, 2/42),with significant difference ( P<0.05). Conclusions:For end-stage deformity of osteoarthritis (valgus or varus >20°), post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases, the rotating hinge knee can provide good clinical improvement effects. For neuromuscular or immune diseases, the incidence of complications was relatively high. The therapeutic effect of patients over 60 years old showed no significant difference in the early postoperative efficacy compared with younger patients, but the complications of elderly patients were much higher than those of younger patients.

Alzheimer's disease(AD)is the most common neurodegenerative disease in the elderly,and its main pathological manifestations include senile plaques formed by β-amyloid deposition and neuronal fibrillar nodules formed by hyperphosphorylation of tau proteins.Lysosome is an important organelle in eukaryotic cells,containing a variety of hydrolytic enzymes that can break down proteins and other biomolecules.It is closely related to intracellular transport and autophagy,and is important for maintaining cellular homeostasis.This review summarizes the interaction between lysosomal dysfunction and the development and progression of AD and the potential therapeutic mechanisms in treating AD by regulating and restoring the functions of lysosomes.Lysosomal dysfunction can lead to neurodegenerative diseases such as AD.Modulation of lysosomal function is a promising treatment strategy for AD.It is expected that more drugs and therapeutic regimens based on this mechanism can be used in the clinical treatment for AD patients in the future.

OBJECTIVE: To characterize a glycosyltransferase (RpUGT1) from Rheum palmatum and investigate its specificity toward flavonoid compounds. METHODS: The RpUGT1 was expressed in Escherichia coli and screened for catalytic activity against a range of flavonoid substrates using a high-throughput HPLC assay method. Mass spectrometry (MS) and nuclear magnetic resonance (NMR) were used to determine the structure of the product. Homology modeling, molecular docking analyses and site-directed mutagenesis studies were conducted to identify key residues responsible for its function. RESULTS: The recombinant RpUGT1 protein exhibited catalytic activity towards various flavonoids. Notably, RpUGT1 catalyzed the glycosylation of isorhamnetin to form 3-O-glucoside and kaempferol to form 7-O-glucoside, utilizing uridine diphosphate (UDP) glucose as the sugar donor. The homology modeling and molecular docking analyses identified key residues responsible for its activity. Subsequent site-directed mutagenesis studies highlighted the crucial role of K307 in catalysis. CONCLUSION These discoveries offer valuable perspectives on the role of the UGT family and establish a groundwork for forthcoming research on the synthesis of flavonoids in plants.

Objective:To explore the early clinical effect of arthroplasty with rotating hinge knee prosthesis in the treatment of severe knee deformity.Methods:A retrospective study was conducted on 55 patients who underwent primary rotating hinge knee arthroplasty at Shanghai Sixth People's Hospital from January 2017 to October 2023, including 19 male patients and 36 female patients, with an average age of 60.9±9.0 years (ranging from 31 to 74 years). The four main indications were end-stage deformity of osteoarthritis (valgus/varus>20°, 16 cases), post-traumatic joint deformity (15 cases), severe joint ligament instability (12 cases), and neuromuscular or immune diseases (12 cases). The patients were divided into two age groups: ≥60 years old group (32 cases) and <60 years old group (23 cases). Various pre-operative and post-operative data, including knee society score (KSS), range of motion (ROM), forgotten joint score (FJS), degree of force line offset and post-operative complications, were collected and compared.Results:All the 55 cases successfully underwent the operation. The operation time was 102.3±15.8 min. The intraoperative blood loss was 63±23.7 ml. The follow-up time was 37.2±7.9 months. KSS clinical score increased from 27.5(12, 45) before surgery to 90.5(85, 95) after surgery ( P<0.001) and the mean score of KSS function increased from 50.4(45, 60) before surgery to 84.3(85, 95) after surgery ( P<0.001), both with significant difference ( P<0.05). Similarly, the average postoperative ROM improved from 97.2°±34.4° to 120.1°±10.9°with significant difference ( P<0.05). The postoperative FJS was 81.0±6.6. Up to the last follow-up, the implant survival rate was 98%[95% CI(90.4%, 99.6%)]. For the all four groups of end-stage deformity of osteoarthritis, post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases, both the KSS score and the ROM of the knee joint were significantly improved. There was no significant difference in neither the KSS score or the ROM of the knee joint between the ≥60 years old group and the <60 years old group ( P>0.05). The incidence of complications was 24% (13/55). The complication rates for patients with end-stage deformity of osteoarthritis, post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases were 12.5% (2/16), 20% (3/15), 25% (3/12), and 41.7% (5/12) respectively, without significant difference. The incidence of complications in elderly patients (85%, 11/13) was much higher than that in younger patients (5%, 2/42),with significant difference ( P<0.05). Conclusions:For end-stage deformity of osteoarthritis (valgus or varus >20°), post-traumatic joint deformity, severe joint ligament instability and neuromuscular or immune diseases, the rotating hinge knee can provide good clinical improvement effects. For neuromuscular or immune diseases, the incidence of complications was relatively high. The therapeutic effect of patients over 60 years old showed no significant difference in the early postoperative efficacy compared with younger patients, but the complications of elderly patients were much higher than those of younger patients.

Objective: To investigate the characteristics of hospitalized injury cases in Huangpu District, Guangzhou City in 2022, so as to provide evidence for optimizing injury prevention interventions. Methods: Data on hospitalized injury cases admitted between January to December 2022 were collected through the hospitalization registry system from 17 healthcare institutions in Huangpu District. The population distribution characteristics, causes of injury, injury sites, duration of hospital stay, and hospitalization costs were descriptively analyzed. Results: A total of 6 729 hospitalized injury cases were reported in Huangpu District in 2022, including 4 277 males and 2 452 females, with a male-to-female ratio of 1.74∶1. The average age was (49.57±19.82) years, with 2 064 cases (30.67%) aged 45 to <60 years and 1 921 cases (28.55%) aged ≥60 years. The median length of hospitalization was 9.00 (interquartile range, 11.00) days, with median hospitalization costs of 15 968.93 (interquartile range, 25 786.69) yuan. In the months of June to August, there were more cases of injury hospitalization,with 1 904 cases accounting for 28.30%. The top three causes of injury were falls (2 895 cases, 43.02%), transportation accidents (1 247 cases, 18.53%) and exposure to inanimate mechanical forces (1 104 cases, 16.41%). The top three injured sites were lower limb injuries (1 850 cases, 27.49%), upper limb injuries (1 596 cases, 23.72%) and other sites (1 178 cases, 17.51%). The three leading causes of injury with longest hospitalization duration were burns and scalds, transport accidents and falls, with the median duration being 12.00 (interquartile range, 8.00) days, 10.00 (interquartile range, 13.00) days and 10.00 (interquartile range, 11.00) days, respectively. The top three injury sites associated with the longest hospitalization duration were others, lower limb injuries, and head and neck injuries, with the median duration being 11.00 (interquartile range, 13.00) days, 11.00 (interquartile range, 11.00) days, and 10.00 (interquartile range, 12.00) days, respectively. The causes of injury associated with higher hospitalization costs were falls and transportation accidents, with the median hospitalization cost being 23 550.13 (interquartile range, 30 087.76) yuan for falls and 20 301.94 (interquartile range, 30 589.86) yuan for transportation accidents. The injury sites associated with higher hospitalization costs were lower limb injuries and upper limb injuries, with the median hospitalization cost being 24 257.32 (interquartile range, 34 145.54) yuan for lower limb injuries and 16 506.33 (interquartile range, 20 052.27) yuan for upper limb injuries. Conclusions In Huangpu District, hospitalized injury mainly occurred among males and individuals aged ≥45 years, with the higher incidence observed between June and August. Fall was the primary cause of injury, while lower limb injuries was the main injury sites. The injury resulted in substantially higher hospitalization costs.

Objective:To assess the clinical efficacy and infection control outcomes of two-stage revision in managing periprosthetic joint infection (PJI) following primary total knee arthroplasty (TKA) utilizing either a low or high constrained prosthesis.Methods:A retrospective analysis was performed on 40 patients who underwent revision TKA in the Sixth People's Hospital Affiliated to Shanghai Jiao Tong University from February 2019 to February 2022. According to the type of prosthesis selected in primary TKA, they were divided into low constrained prosthesis group and high constrained prosthesis group. There were 28 patients (28 knees) in the low constrained group, including 12 males and 16 females, aged 69.0(63.0, 74.0) years, with a body mass index of 25.18±0.55 kg/m 2. And there were 12 patients (12 knees) in the high-constrained group, including 5 males and 7 females, aged 66.5(65.0, 71.5) years, with a body mass index of 23.94±0.51 kg/m 2. All patients underwent two-stage revision surgery, with RHK used in 1 case and LCCK in 27 cases in the low-constrained prosthesis group. In the high-constrained prosthesis group, 3 patients were treated with RHK, 1 patient with PFC Sigma MBT, and 8 patients with LCCK. The preoperative and postoperative range of motion (ROM), Knee Society score (KSS), and postoperative infection control rate were compared between the two groups. Results:All patients were followed up. The follow-up time was 22.79±8.02 months in the low-constrained prosthesis group and 23.92±7.04 months in the high-constrained prosthesis group, with no significant difference between the two groups ( t=0.426, P=0.680). At the last follow-up, the KSS and ROM in the low-constrained prosthesis group were 77.96±9.74 and 93.48°±7.45°, respectively, significantly higher than 38.93±8.01 and 68.89°±9.44° before the operation ( P<0.05). The KSS score and ROM in the high-constrained prosthesis group were 67.83±8.31 and 80.08°±5.89° at the last follow-up, which were also significantly higher than those before operation (34.25±6.31 and 66.50°±10.48°, P<0.05). There was no significant difference in KSS and ROM between the two groups before operation ( P>0.05), but the KSS score and ROM in the low-constrained prosthesis group were significantly higher than those in the high-constrained prosthesis group at the last follow-up ( P<0.05). Bacterial culture results revealed that the primary infectious agents were coagulase-negative Staphylococcus and Staphylococcus aureus, with an overall infection control rate of 80% (32/40). The infection control rate was 89% (25/28) in the low-constrained prosthesis group and 58% (7/12) in the high-constrained prosthesis group, but the difference between the two groups was not statistically significant (χ 2=3.283, P=0.070). Conclusion:Two-stage revision effectively controls PJI, and the clinical outcomes of two-stage revision for PJI after primary TKA with a high-constrained prosthesis are inferior to those with a low-constrained prosthesis. Further exploration is needed to enhance efficacy.

Objective:To investigate the bidirectional causal relationship between schizophrenia and suicide or intentional self-harm using a Mendelian randomization (MR) approach.Methods:Using pooled data from a large-scale genome-wide association study, genetic loci that were independent of each other and associated with schizophrenia and suicide or intentional self-harm in populations of European ancestry were selected as instrumental variables. The data for schizophrenia included 76 755 patients with schizophrenia and 243 649 controls. Data for suicide or intentional self-harm included 1 058 patients with suicide or intentional self-harm and 307 942 controls. The inverse variance weighting (IVW) and weighted median methods of MR analysis were used to explore the bidirectional causality of schizophrenia and suicide or intentional self-harm using the ratio of ratios ( OR) as an evaluation index. Heterogeneity between individual single nucleotide polymorphism (SNP) was assessed by Cochran′s Q test. Mendelian randomization polymorphism residuals and outliers (MR-PRESSO) were used to detect SNP outliers, and MR-Egger regression tests were performed to examine the horizontal pleiotropy of SNPs. A "leave-one-out" sensitivity analysis was performed to test whether the MR study was influenced by individual SNPs. Results:The IVW approach showed that schizophrenia increased the risk of suicide or intentional self-harm ( OR=1.297, 95% CI=1.154-1.457, P<0.001). In addition, the above relationship was confirmed in the weighted median ( OR=1.232, 95% CI=1.038-1.461, P=0.017). Conversely, suicide or intentional self-harm was not causally associated with schizophrenia ( OR=0.969, 95% CI=0.927—1.012, P=0.157), again confirmed by the weighted median method. The Cochran′s Q test, MR-PRESSO and MR-Egger regression tests did not show heterogeneity or horizontal pleiotropy between instrumental variables. The "leave-one-out" sensitivity analysis confirmed that no single SNP had a disproportionate effect on the overall outcome. Conclusion:Schizophrenia is significantly and causally associated with an increased risk of suicide or intentional self-harm.

Objective:To investigate the bidirectional causal relationship between schizophrenia and suicide or intentional self-harm using a Mendelian randomization (MR) approach.Methods:Using pooled data from a large-scale genome-wide association study, genetic loci that were independent of each other and associated with schizophrenia and suicide or intentional self-harm in populations of European ancestry were selected as instrumental variables. The data for schizophrenia included 76 755 patients with schizophrenia and 243 649 controls. Data for suicide or intentional self-harm included 1 058 patients with suicide or intentional self-harm and 307 942 controls. The inverse variance weighting (IVW) and weighted median methods of MR analysis were used to explore the bidirectional causality of schizophrenia and suicide or intentional self-harm using the ratio of ratios ( OR) as an evaluation index. Heterogeneity between individual single nucleotide polymorphism (SNP) was assessed by Cochran′s Q test. Mendelian randomization polymorphism residuals and outliers (MR-PRESSO) were used to detect SNP outliers, and MR-Egger regression tests were performed to examine the horizontal pleiotropy of SNPs. A "leave-one-out" sensitivity analysis was performed to test whether the MR study was influenced by individual SNPs. Results:The IVW approach showed that schizophrenia increased the risk of suicide or intentional self-harm ( OR=1.297, 95% CI=1.154-1.457, P<0.001). In addition, the above relationship was confirmed in the weighted median ( OR=1.232, 95% CI=1.038-1.461, P=0.017). Conversely, suicide or intentional self-harm was not causally associated with schizophrenia ( OR=0.969, 95% CI=0.927—1.012, P=0.157), again confirmed by the weighted median method. The Cochran′s Q test, MR-PRESSO and MR-Egger regression tests did not show heterogeneity or horizontal pleiotropy between instrumental variables. The "leave-one-out" sensitivity analysis confirmed that no single SNP had a disproportionate effect on the overall outcome. Conclusion:Schizophrenia is significantly and causally associated with an increased risk of suicide or intentional self-harm.

Purpose: Long non-coding RNAs (lncRNAs) may act as oncogenes in small-cell lung cancer (SCLC). Exosomes containing lncRNAs released from cancer-associated fibroblasts (CAF) accelerate tumorigenesis and confer chemoresistance. This study aimed to explore the action mechanism of the CAF-derived lncRNA maternally expressed gene 3 (MEG3) on cisplatin (DDP) chemoresistance and cell processes in SCLC. Materials and Methods: Quantitative real-time PCR was conducted to determine the expression levels of MEG3, miR-15a-5p, and CCNE1. Cell viability and metastasis were measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-h-tetrazolium bromide and invasion assays, respectively. A xenograft tumor model was developed to confirm the effect of MEG3 overexpression on SCLC progression in vivo. Relationships between miR-15a-5p and MEG3/CCNE1 were predicted using StarBase software and validated by dual luciferase reporter assay. Western blotting was used to determine protein levels. A co-culture model was established to explore the effects of exosomes on MEG3 expression in SCLC cell lines. Results: MEG3 was overexpressed in SCLC tissues and cells. MEG3 silencing significantly repressed cell viability and metastasis in SCLC. High expression of MEG3 was observed in CAF-derived conditioned medium (CM) and exosomes, and promoted chemoresistance and cancer progression. Additionally, MEG3 was found to serve as a sponge of miR-15a-5p to mediate CCNE1 expression. Overexpression of miR-15a-5p and knockout of CCNE1 reversed the effects of MEG3 overexpression on cell viability and metastasis. Conclusion MEG3 lncRNA released from CAF-derived exosomes promotes DDP chemoresistance via regulation of a miR-15a-5p/CCNE1 axis. These findings may provide insight into SCLC therapy.