Objective The relationship between serum uric acid(UA)levels and gait kinematics characteristics in patients with cerebral small vessel disease(CSVD)was investigated.Methods Retrospective analysis was conducted on patients with CSVD from outparient clinics of the Neurology and Rehabilitation Department of Zhongshan Hospital affiliated with Guangzhou University of Chinese Medicine from January 2023 to December 2023.The general information of patients were collected and the gait of patients was analyzed using three-dimensional gait analysis.Patients were then divided into mild gait disorder group(0-1 points),moderate gait disorder group(2-3 points),and severe gait dysfunction group(4-5 points)based on gait results.The total burden of CSVD imaging and serum results such as UA were collected.The relationship between UA level and CSVD gait disorders was analyzed.Results This study recruited 105 CSVD patients.Patients were divided into different groups based on the severity of their gait disorder including 40 in the mild group,49 in the moderate group,and 16 in the severe group.The blood uric acid level in the moderate group(358.43±13.44)μmol/L was higher than that in the mild group(336.00±12.48)μmol/L,and the blood uric acid level in the severe group(289.94±11.88)μmol/L was lower than that in the mild and moderate groups(P<0.05).The MoCA score in the severe gait disorder group(21.38±0.13)was lower than that in the mild and moderate groups(28.05±0.09 vs.25.22±0.10)(P<0.05).The step width of the CSVD severe load group was(13.26±2.80)cm compared to the light and moderate load groups[(11.22±1.70)cm vs.(11.65±2.70)cm]increased(P<0.05),and the left swing phase in the severe group(35.90%)decreased compared to the mild and moderate groups(38.50%vs.37.20%)(P<0.05).Spearman correlation analysis showed a negative correlation between UA levels and CMB(r=-0.20,P=0.04).Hyperuricemia was negatively correlated with brain atrophy(r=-0.20,P=0.04).In patients with mild to moderate gait disorders,there was a positive correlation between hyperuricemia and the total burden of gait disorders(r=0.25,P=0.02),and hyperuricemia and right gait speed(r=-0.22,P=0.04),Right stride(r=-0.29,P<0.01),Left step speed(r=-0.32,P<0.01),Left step frequency(r=-0.29,P<0.01),The left stride was negatively correlated(r=-0.26,P=0.01).Conclusion In CSVD patients with mild to moderate gait disorders,the levels of uric acid and hyperuricemia are positively correlated with the total burden of gait disorders.The gait disorders are mainly characterized by reduced bilateral pace,bilateral stride,and left step frequency.

Central retinal vein occlusion(CRVO)is a retinal vascular disorder that significantly impairs vision, with its underlying mechanisms involving complex interactions across multiple biological systems. This article provides a systematic review of the pathological mechanisms associated with CRVO, emphasizing critical factors such as endothelial dysfunction, arteriosclerosis, thrombophilia, inflammation, and oxidative stress. The pathological mechanisms of CRVO are characterized by arteriosclerosis, which obstructs venous return through a dual mechanism involving mechanical compression and endothelin-1-mediated contraction; endothelial dysfunction, which exacerbates disturbances in blood flow; genetic and acquired coagulation abnormalities that disrupt hemostatic balance and promote thrombosis; and the synergistic effects of inflammation and oxidative stress that activate cytokines, thereby aggravating ischemia and vascular leakage. Innovatively, this review explores emerging mechanisms such as miRNA-mediated vascular regulation via exosomes, gut microbiota-retina crosstalk through the “gut-eye axis,” and systemic metabolic interactions that link local retinal lesions to broader dysregulation of CRVO. These insights underscore the importance of integrated eye-system interventions and provide a theoretical foundation for advancing early biomarker discovery, multitarget therapeutics, and personalized treatment paradigms. By bridging localized pathology and systemic mechanisms, this work promotes a transformative shift toward an integrative medicine model in the diagnosis and management of CRVO.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

Objectives:To investigate the clinical efficacy of staged percutaneous endoscopic posterior decom-pression for treating multi-segment thoracic ossification of ligamentum flavum(mTOLF).Methods:The clinical data of 16 patients with mTOLF who were treated with staged percutaneous endoscopic posterior decompres-sion at our hospital between June 2021 and June 2023 were retrospectively analyzed,including 9 males and 7 females,aged 46-67(55.4±6.8)years old.The preoperative imaging examinations of the patients indicated multi-segment ossification of ligamentum flavum,including double segments in 14 cases and triple segments in 2 cases.The responsible segments were as follows:upper thoracic spine(T1-T4)in 4 cases,middle thoracic spine(T5-T9)in 6 cases,and lower thoracic spine(T10-T12)in 24 cases.Staged percutaneous endoscopic posterior decompression was performed for mTOLF,targeting only one responsible segment in each surgery.The operative time,blood loss,hospitalization days,and complications were recorded.The Oswestry disability index(ODI)and the modified Japanese Orthopaedic Association(mJOA)11-point scale scores were recorded preoperatively,on 3d postoperatively,and at the final follow-up,and the mJOA improvement rate at the final follow-up was calculated.Statistical analysis was performed to evaluate the clinical efficacy.The spinal canal area and the anterior-posterior spinal canal diameter were measured on CT images preoperatively,on 3d post-operatively,and at the final follow-up to evaluate the improvement of imaging findings.Results:All the 16 patients successfully completed the surgery,and no cerebrospinal fluid leakage or permanent lower limb paral-ysis occurred except for one dural tear during operation.The operative time was 80-205min(150.2±36.1min),blood loss was 30-70mL(50.3±12.4mL),hospitalization days were 9-15d(10.8±1.8d)and the follow-up time ranged from 9-20(14.3±3.2)months.The mJOA scores and ODIs before surgery,on 3d after surgery,and at the final follow-up were 5.7±1.3,7.1±1.3,8.5±1.4,and(41.4±1.8)％,(17.8±1.6)％,(15.6±1.3)％,respectively,which were both significantly improved on 3d postoperatively and at final follow-up compared with those val-ues before operation(P＜0.05).The mJOA recovery rate was 28.6％-100％[(56.1±19.3)％],and according to the mJOA evaluation criteria,the outcomes were classified as excellent in 3 cases,good in 9 cases,fair in 4 cases,and poor in no case,with an excellent and good rate of 75.0％.The spinal canal area and anterior-posterior diameter before surgery,on 3d after surgery,and at the final follow-up were 76.7±12.5mm2,159.9±22.1mm2,157.7±21.6mm2,and 7.4±0.5mm,15.5±0.9mm,15.3±0.9mm,respectively.Both the spinal canal area and anterior-posterior diameter on 3d postoperatively and at the final follow-up significantly increased com-pared to preoperative values(P＜0.05).Conclusions:Staged percutaneous endoscopic posterior decompression for treating mTOLF is safe and effective,and yields satisfactory clinical outcomes.

Objective The relationship between serum uric acid(UA)levels and gait kinematics characteristics in patients with cerebral small vessel disease(CSVD)was investigated.Methods Retrospective analysis was conducted on patients with CSVD from outparient clinics of the Neurology and Rehabilitation Department of Zhongshan Hospital affiliated with Guangzhou University of Chinese Medicine from January 2023 to December 2023.The general information of patients were collected and the gait of patients was analyzed using three-dimensional gait analysis.Patients were then divided into mild gait disorder group(0-1 points),moderate gait disorder group(2-3 points),and severe gait dysfunction group(4-5 points)based on gait results.The total burden of CSVD imaging and serum results such as UA were collected.The relationship between UA level and CSVD gait disorders was analyzed.Results This study recruited 105 CSVD patients.Patients were divided into different groups based on the severity of their gait disorder including 40 in the mild group,49 in the moderate group,and 16 in the severe group.The blood uric acid level in the moderate group(358.43±13.44)μmol/L was higher than that in the mild group(336.00±12.48)μmol/L,and the blood uric acid level in the severe group(289.94±11.88)μmol/L was lower than that in the mild and moderate groups(P<0.05).The MoCA score in the severe gait disorder group(21.38±0.13)was lower than that in the mild and moderate groups(28.05±0.09 vs.25.22±0.10)(P<0.05).The step width of the CSVD severe load group was(13.26±2.80)cm compared to the light and moderate load groups[(11.22±1.70)cm vs.(11.65±2.70)cm]increased(P<0.05),and the left swing phase in the severe group(35.90%)decreased compared to the mild and moderate groups(38.50%vs.37.20%)(P<0.05).Spearman correlation analysis showed a negative correlation between UA levels and CMB(r=-0.20,P=0.04).Hyperuricemia was negatively correlated with brain atrophy(r=-0.20,P=0.04).In patients with mild to moderate gait disorders,there was a positive correlation between hyperuricemia and the total burden of gait disorders(r=0.25,P=0.02),and hyperuricemia and right gait speed(r=-0.22,P=0.04),Right stride(r=-0.29,P<0.01),Left step speed(r=-0.32,P<0.01),Left step frequency(r=-0.29,P<0.01),The left stride was negatively correlated(r=-0.26,P=0.01).Conclusion In CSVD patients with mild to moderate gait disorders,the levels of uric acid and hyperuricemia are positively correlated with the total burden of gait disorders.The gait disorders are mainly characterized by reduced bilateral pace,bilateral stride,and left step frequency.

Objective:To investigate the effect of PIK3CA mutations on the tumor immune microenvironment in Luminal breast cancer and evaluate the potential of Alpelisib-loaded pH-responsive polymer micelles in modulating the tumor immune microenvironment.Methods:PIK3CA mutations in breast cancer were analyzed using bioinformatics tools.A mouse xenograft model of Luminal breast cancer harboring a PIK3CA mutation was established,and alterations in the tumor immune microenvironment were examined using mass cytometry(CyTOF).During the period from August 2004 to December 2008 in Tianjin Medical University Cancer Hospital,tissue biopsies of 62 Luminal breast cancer patients in the BRCA cohort were collected Study the relationship between PIK3CA mutations and tumor immune microenvironment at the organizational level.Alpelisib-loaded polymer micelles(Alpelisib@MSPM)were synthesized,characterized,and evaluated for thera-peutic efficacy in Luminal breast cancer with PIK3CA mutations.Results:PIK3CA is one of the most frequently mutated genes in breast can-cer,with the highest prevalence in Luminal subtypes.CyTOF analysis demonstrated that PIK3CA mutations contribute to a tumor immun-osuppressive microenvironment in xenografts.Multiplex fluorescence immunohistochemistry revealed that PIK3CA-mutated tumors exhib-ited more infiltration of myeloid-derived suppressor cells(MDSCs)and less infiltration of CD8? T cells.The synthesized Alpelisib-loaded pH-re-sponsive polymer micelles had an average size of approximately 127 nm.Treatment with Alpelisib and Alpelisib@MSPM reduced tumor growth in mice with PIK3CA-mutated Luminal breast cancer.Notably,the proportion of MDSCs decreased,whereas CD8? T cell infiltration in-creased significantly,with the more pronounced effect observed in the Alpelisib@MSPM treatment group.Conclusions:PIK3CA mutations drive the formation of a tumor immunosuppressive microenvironment in Luminal breast cancer.Targeted Alpelisib delivery via pH-respons-ive polymer micelles significantly enhances therapeutic efficacy in PIK3CA-mutated breast cancer.

OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin,and provide data support for the enhancement of relevant policies.METHODS In this research,the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin(October-December 2021 and October-December 2022),and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost(DDDc)of various types of insulins.The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated,using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income(i.e.the proportion of annual expenditure)as an indicator.RESULTS After the specialized centralized procurement,DDDc of various types of insulins decreased by 20.7%-71.8%,with an average reduction of 45.7%.Moreover,the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin.The reduction in the proportion of annual expenditure on insulin ranged from 24.3%to 73.4%,with an average decrease of 48.5%.Premixed insulin analogs experienced the greatest reduction(73.4%).Following the specialized centralized procurement,DDDc of insulin decreased in all provinces.Except for Guangxi(10.2%),the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%.CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability,thereby alleviating the economic pressure on patients with diabetes.There are notable cost disparities among provinces and among insulin categories,which require attention.

OBJECTIVE To further standardize the dispensing management standard of intravenous infusion drugs for clinical trials in pharmacy intravenous admixture services (PIVAS),and provide reference for medical institutions to provide high-quality pharmaceutical services.METHODS Initiated by PIVAS Group,Hospital Pharmacy Professional Committee,Shanghai Pharmaceutical Association,jointly led by Longhua Hospital,Shanghai University of Traditional Chinese Medicine and Shanghai Geriatric Medical Center,a writing group was established by PIVAS experts from multiple medical institutions to discuss the basic requirements and dispensing process of intravenous infusion drugs for clinical trials in PIVAS.The experts from the leading unit sorted out,summarized,analyzed,fed back and revised the opinions,and finally reached Expert Consensus on Dispensing Management of Intravenous Infusion Drugs for Clinical Trials in PIVAS.RESULTS & CONCLUSIONS The main contents of this consensus include information management,operation process,fund management and document management of intravenous infusion drugs for clinical trials in PIVAS.This consensus establishes a more standardized model for dispensing management of intravenous infusion drugs for clinical trials in PIVAS,by standardizing clinical trail drug management operational procedures,accurately recording and preserving drug-related information,with the aim of achieving standardized and meticulous management of PIVAS's receipt of clinical trial drugs.