Objective To investigate the effect of tirofiban combined with oxiracetam on acute anterior circulation progressive cerebral infarction.Methods A total of 171 patients with acute anteri-or circulation progressive cerebral infarction from October 2022 to January 2024 were enrolled and ran-domly divided into three groups using a random number table.The control group of 57 patients re-ceived conventional treatment,the observation group A received tirofiban in addition to conventional treatment,and the observation group B received oxiracetam on the basis of observation group A's treat-ment.The effectiveness indicators[including the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis and modified Rankin Scale(MRS)scores at 90 days after treatment,as well as the National Institutes of Health Stroke Scale(NIHSS)scores at 7 and 14 days after treatment and their differences from baseline],cognitive function[as-sessed using the Montreal Cognitive Assessment(MOCA)],and safety indicators(incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treat-ment)were compared among the three groups.Results There were no statistically significant differ-ences in the rates of neurological improvement and neurological deterioration at 14 days after treatment,the rate of good prognosis,and MRS scores at 90 days after treatment among the three groups(P＞0.05).There were statistically significant differences in NIHSS scores between baseline and 7 and 14 days after treatment in all three groups(P＜0.05),and the differences in NIHSS scores from baseline at the above time points were higher in observation group B than in observation group A and the control group(P＜0.05).There were no statistically significant differences in MOCA scores among the three groups before treatment(P＞0.05);however,the MOCA scores in the observation group B were higher than those in observation group A and the control group at 14,30,and 90 days after treatment(P＜0.05).There were no statistically significant differences in the incidence rates of symptomatic intracranial hemorrhage,fatal intracranial hemorrhage,and mortality at 90 days after treatment among the three groups(P＞0.05).Conclusion Tirofiban combined with oxiracetam can improve cognitive function in patients with acute anterior circulation progressive cerebral infarc-tion without increasing the risk of hemorrhage,and has better prognosis.

Objective:To investigate the regulatory effect of leptin via the JAK2/STAT3 pathway on the core-binding factor β-subunit (CBFβ) and its molecular mechanism in promoting chondrocyte apoptosis.Methods:A total of five patients undergoing total knee arthroplasty due to knee osteoarthritis (OA group) and five patients undergoing amputation due to trauma (amputation group) were enrolled, and knee cartilage samples were obtained intraoperatively. Western blotting was used to detect the protein expression levels of leptin, CBFβ, matrix metalloproteinase-1 (MMP1), and MMP13. Flow cytometry was performed to determine the optimal treatment duration and concentration of leptin. Chondrocytes were divided into the following groups based on treatment conditions: control group (untreated chondrocytes), leptin group (chondrocytes treated with 50 ng/ml leptin), negative leptin group (chondrocytes transfected with a non-targeting sequence as a control), and leptin+shCBFβ group (chondrocytes transfected with shCBFβ to inhibit CBFβ expression). Apoptosis and the expression levels of MMP1 and MMP13 were analyzed in the four groups. Additionally, chondrocytes were categorized into the following groups for further analysis: control group (untreated cells), leptin group (cells stimulated with 50 ng/ml leptin for 48 h), AG490 group (cells treated with the JAK2/STAT3 inhibitor AG490), and leptin+AG490 group (cells pretreated with AG490 for 2 h followed by 50 ng/ml leptin stimulation for 48 h). The protein expression levels of CBFβ, MMP1, and MMP13, as well as the apoptosis rate, were examined in the four groups.Results:The relative expression levels of leptin, CBFβ, MMP1, and MMP13 in the amputation group were 0.66±0.06, 0.69±0.06, 0.74±0.05, and 0.41±0.03, respectively, which were significantly lower than those in the OA group (1.04±0.10, 1.06±0.09, 0.95±0.04, and 0.99±0.09, respectively) ( P<0.05). The optimal treatment duration and concentration of leptin were determined to be 48 h and 50 ng/ml, respectively. The expression levels of MMP1 and MMP13 significantly differed among the control, leptin, negative leptin, and leptin+shCBFβ groups ( P<0.05). Specifically, the leptin group showed higher expression levels compared to the control group, while the leptin+shCBFβ group exhibited lower expression levels than the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the four groups were 4.55%±1.30%, 22.52%±2.03%, 22.03%±2.01%, and 5.15%±0.91%, respectively, with significant differences ( F=114.066, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+shCBFβ group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Similarly, significant differences were observed in the expression levels of CBFβ, MMP1, and MMP13 among the control, leptin, AG490, and leptin+AG490 groups ( P<0.05). The expression levels in the leptin group were higher than those in the control group, while the leptin+AG490 group exhibited lower expression levels compared to the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the control, leptin, AG490, and leptin+AG490 groups were 5.19±0.94%, 31.52±2.63%, 5.51±1.41%, and 10.47±0.85%, respectively, with significant differences ( F=117.104, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+AG490 group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Conclusion:Leptin promotes CBFβ expression via the JAK2/STAT3 pathway, leading to chondrocyte apoptosis and extracellular matrix degradation.

BACKGROUND:SOX5 is an important transcription factor of the SRY-related HMG-box(SOX)family,which plays a key role in regulating the expression of genes related to bone development and remodeling,especially during osteoblast differentiation and chondrocyte maturation,through its unique HMG box DNA structural domains in concert with SOX6 and SOX9.In addition,the expression and activity of SOX5 and its family are regulated by a variety of diseases and different forms of exercise,among other factors,suggesting that SOX5 and its family have the potential to be effective as drugs and therapeutics to ameliorate related diseases in the future.OBJECTIVE:To provide new perspectives for future research on SOX5 and to provide scientific basis for the application of exercise intervention and drug therapy in the prevention and treatment of bone diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 2001 to June 2024,and the search terms were"SRY-related HMG-box5,SOX5,Bone"in Chinese and English,respectively.After screening,analysis and summarization,105 articles were included in the final review.RESULTS AND CONCLUSION:(1)Role of SOX5 in bone development:SOX5 is an important member of the SOX family,which plays a central role in the regulation of skeletal development,bone metabolism and cartilage formation.In synergy with SOX6 and SOX9,SOX5 activates gene expression in osteoblasts and chondrocytes by binding to specific DNA sequences to regulate bone formation and bone remodeling.(2)Abnormal expression of SOX5 is closely related to bone and joint diseases such as chondrodysplasia,osteoporosis and osteoarthritis,suggesting that it may be a key regulator of these diseases.Currently,a variety of drugs may be used to treat bone metabolism-related diseases by regulating SOX5 and its family,and upregulation of SOX5 in mesenchymal stem cells may be effective in improving the symptoms of bone metabolism disease patients in bone tissue engineering.(3)Exercise may effectively prevent osteoporosis and related bone diseases by enhancing bone metabolism and promoting osteoblast differentiation and bone density increase.This mechanism of action may be related to the specific regulatory mechanism of SOX5,especially in different types,intensities and durations of exercise need to be further explored and studied.In conclusion,SOX5 has an important regulatory role in bone development,chondrogenesis,and prevention of bone diseases,and its activity is regulated by a variety of factors,while exercise intervention provides a new scientific basis for the treatment of bone diseases.

Objective:To investigate the regulatory effect of leptin via the JAK2/STAT3 pathway on the core-binding factor β-subunit (CBFβ) and its molecular mechanism in promoting chondrocyte apoptosis.Methods:A total of five patients undergoing total knee arthroplasty due to knee osteoarthritis (OA group) and five patients undergoing amputation due to trauma (amputation group) were enrolled, and knee cartilage samples were obtained intraoperatively. Western blotting was used to detect the protein expression levels of leptin, CBFβ, matrix metalloproteinase-1 (MMP1), and MMP13. Flow cytometry was performed to determine the optimal treatment duration and concentration of leptin. Chondrocytes were divided into the following groups based on treatment conditions: control group (untreated chondrocytes), leptin group (chondrocytes treated with 50 ng/ml leptin), negative leptin group (chondrocytes transfected with a non-targeting sequence as a control), and leptin+shCBFβ group (chondrocytes transfected with shCBFβ to inhibit CBFβ expression). Apoptosis and the expression levels of MMP1 and MMP13 were analyzed in the four groups. Additionally, chondrocytes were categorized into the following groups for further analysis: control group (untreated cells), leptin group (cells stimulated with 50 ng/ml leptin for 48 h), AG490 group (cells treated with the JAK2/STAT3 inhibitor AG490), and leptin+AG490 group (cells pretreated with AG490 for 2 h followed by 50 ng/ml leptin stimulation for 48 h). The protein expression levels of CBFβ, MMP1, and MMP13, as well as the apoptosis rate, were examined in the four groups.Results:The relative expression levels of leptin, CBFβ, MMP1, and MMP13 in the amputation group were 0.66±0.06, 0.69±0.06, 0.74±0.05, and 0.41±0.03, respectively, which were significantly lower than those in the OA group (1.04±0.10, 1.06±0.09, 0.95±0.04, and 0.99±0.09, respectively) ( P<0.05). The optimal treatment duration and concentration of leptin were determined to be 48 h and 50 ng/ml, respectively. The expression levels of MMP1 and MMP13 significantly differed among the control, leptin, negative leptin, and leptin+shCBFβ groups ( P<0.05). Specifically, the leptin group showed higher expression levels compared to the control group, while the leptin+shCBFβ group exhibited lower expression levels than the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the four groups were 4.55%±1.30%, 22.52%±2.03%, 22.03%±2.01%, and 5.15%±0.91%, respectively, with significant differences ( F=114.066, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+shCBFβ group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Similarly, significant differences were observed in the expression levels of CBFβ, MMP1, and MMP13 among the control, leptin, AG490, and leptin+AG490 groups ( P<0.05). The expression levels in the leptin group were higher than those in the control group, while the leptin+AG490 group exhibited lower expression levels compared to the leptin group ( P<0.05). The apoptosis rates of chondrocytes in the control, leptin, AG490, and leptin+AG490 groups were 5.19±0.94%, 31.52±2.63%, 5.51±1.41%, and 10.47±0.85%, respectively, with significant differences ( F=117.104, P<0.001). The apoptosis rate in the leptin group was significantly higher than that in the control group, while the leptin+AG490 group exhibited a significantly lower apoptosis rate than the leptin group ( P<0.05). Conclusion:Leptin promotes CBFβ expression via the JAK2/STAT3 pathway, leading to chondrocyte apoptosis and extracellular matrix degradation.

BACKGROUND:SOX5 is an important transcription factor of the SRY-related HMG-box(SOX)family,which plays a key role in regulating the expression of genes related to bone development and remodeling,especially during osteoblast differentiation and chondrocyte maturation,through its unique HMG box DNA structural domains in concert with SOX6 and SOX9.In addition,the expression and activity of SOX5 and its family are regulated by a variety of diseases and different forms of exercise,among other factors,suggesting that SOX5 and its family have the potential to be effective as drugs and therapeutics to ameliorate related diseases in the future.OBJECTIVE:To provide new perspectives for future research on SOX5 and to provide scientific basis for the application of exercise intervention and drug therapy in the prevention and treatment of bone diseases.METHODS:CNKI and PubMed databases were searched for relevant literature published from 2001 to June 2024,and the search terms were"SRY-related HMG-box5,SOX5,Bone"in Chinese and English,respectively.After screening,analysis and summarization,105 articles were included in the final review.RESULTS AND CONCLUSION:(1)Role of SOX5 in bone development:SOX5 is an important member of the SOX family,which plays a central role in the regulation of skeletal development,bone metabolism and cartilage formation.In synergy with SOX6 and SOX9,SOX5 activates gene expression in osteoblasts and chondrocytes by binding to specific DNA sequences to regulate bone formation and bone remodeling.(2)Abnormal expression of SOX5 is closely related to bone and joint diseases such as chondrodysplasia,osteoporosis and osteoarthritis,suggesting that it may be a key regulator of these diseases.Currently,a variety of drugs may be used to treat bone metabolism-related diseases by regulating SOX5 and its family,and upregulation of SOX5 in mesenchymal stem cells may be effective in improving the symptoms of bone metabolism disease patients in bone tissue engineering.(3)Exercise may effectively prevent osteoporosis and related bone diseases by enhancing bone metabolism and promoting osteoblast differentiation and bone density increase.This mechanism of action may be related to the specific regulatory mechanism of SOX5,especially in different types,intensities and durations of exercise need to be further explored and studied.In conclusion,SOX5 has an important regulatory role in bone development,chondrogenesis,and prevention of bone diseases,and its activity is regulated by a variety of factors,while exercise intervention provides a new scientific basis for the treatment of bone diseases.

Objective:To retrospectively analyze the anesthetic management characteristics of children undergoing resection of pheochromocytoma and paraganglioma (PPGL).Methods:The clinical data from patients undergoing resection of PPGL and confirmed histologically from January 1, 2010 to June 30, 2023 were retrospectively collected. The baseline characteristics, intraoperative conditions and postoperative complications were recorded.Results:The clinical data from 47 pediatric patients were analyzed. The overall incidence of hemodynamic instability events was 68% (32 cases). Lowering preoperative blood pressure to normal levels and the maximum diameter of tumor≥6 cm was helpful in reducing the incidence of the intraoperative hemodynamic instability events ( P<0.05). Postoperative hypotension developed in 7 cases, acute left heart failure in 1 case, arrhythmia in 1 case, adrenocortical insufficiency in 4 cases, and pulmonary infection in 13 cases. Conclusions:Thorough preoperative preparation, evidence-based anesthetic management, and meticulous postoperative vital sign monitoring can increase the perioperative safety for children undergoing resection of PPGL, thereby reducing the incidence of complications.

Objective:To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors.Methods:A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined.Results:Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion ( P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas ( P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA ( P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions:MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

Objective To explore the death characteristics and the potential years of life lost from chronic obstructive pulmonary disease (COPD) among residents in Pudong New Area of Shanghai from 2002 to 2019, so as to provide a reference for formulating corresponding prevention and control strategies for chronic obstructive pulmonary disease. Methods The death data of chronic obstructive pulmonary disease was extracted from the Pudong New Area's death surveillance system. Crude mortality, age-standardized mortality, potential years of life lost (PYLL), average years of life lost (AYLL) and annual percent change (APC) of chronic obstructive pulmonary disease deaths were calculated to analyze the situation of COPD death in Pudong New Area. Results The crude mortality and age-standardized mortality of chronic obstructive pulmonary disease among residents in Pudong New Area between 2002 and 2019 were 64.94/100,000 and 21.04/100 000, respectively. The chronic obstructive pulmonary disease showed a downward trend (APC=-2.05%, Z=- 5.342, P<0.001), and the standardized mortality rate decreased year by year (APC=-6.23%, Z=-13.052, P<0.001). The crude mortality and age-standardized rates in male residents were both higher than those in females (Z-crude mortality=46.471, P<0.001, Z-standardized mortality=-48.961, P<0.001). The PYLL of chronic obstructive pulmonary disease was 16,997 years, the PYLL rate was 0.34‰, and the AYLL was 0.53 years per person. Conclusion From 2002 to 2019, the mortality of chronic obstructive pulmonary disease among residents in Pudong New Area was relatively high and caused serious life loss. Both crude mortality and age-standardized rate showed a downward trend during the study period. Comprehensive prevention and control measures should be further developed.

Objective To explore the epidemiological characteristics and the potential years of life lost of gynecological malignant tumors among female residents in Pudong New Area of Shanghai between 2002 and 2019. Methods Crude mortality rate (CMR), age-standardized mortality rate (SMR), potential years of life lost (PYLL), average years of life lost (AYLL) and annual percent change (APC) of the cervical cancer，uterine cancer and ovarian cancer deaths were calculated to analyze the mortality situation of gynecological malignant tumors among female residents in Pudong New Area. Results The crude mortality rate were 2.65/100 000, 2.44/100 000 , 4.55/100 000, and age-standardized mortality rate were 1.33/100 000, 1.06/100 000, 2.26/100 000, respectively, among female residents in Pudong New Area during 2002 to 2019. In the study period, both the crude mortality rate and the age-standardized mortality rate of cervical cancer rose over the years; Both the crude mortality rate and the age-standardized mortality rate of uterine cancer kept stable; The crude mortality rate of ovarian cancer showed an upward trend, and the age-standardized mortality rate kept stable. The PYLL of cervical cancer was 7335 years, the PYLL rate was 0.30‰, and the AYLL was 11.20 years per person; The PYLL of uterine cancer was 3556 years, the PYLL rate was 0.14‰, and the AYLL was 5.90 years per person; The PYLL of uterine cancer was 10017 years, the PYLL rate was 0.41‰, and the AYLL was 8.91 years per person. Conclusion The mortality rate of cervical cancer and ovarian cancer rose over years, and the mortality of uterine cancer kept stable among female residents in Pudong New Area during 2002 to 2019. The gynecological malignant tumors caused severe disease burden.

Objective:To investigate the epidermal growth factor receptor (EGFR) mutation rate, mutation characteristics and distribution characteristics of different mutation types in patients with non-small cell lung cancer (NSCLC) in Fuyang of Yunnan province, to provide the clinical individualized targeted therapy of NSCLC in this region.Methods:A total of 328 NSCLC patients whose native place were Fuyuan and who underwent EGFR test in Fuyuan County People's Hospital in Yunnan Province from January 2018 to August 2020 were selected, and their clinical data such as gender, age, ethnicity, pathological type and the results of EGFR test were collected for statistical analysis.Results:The EGFR mutation rate of NSCLC patients was 40.55% (133/328). The EGFR mutation rate of female patients was higher than that of males ( P < 0.01). The EGFR mutation rate showed a downward trend with age, the EGFR mutation rate of patients ≤ 60 years old was higher than that of patients > 60 years old ( P = 0.014). The EGFR mutation rate in ethnic minority was not statistically different from Han nationality ( P = 0.789). The EGFR mutation rate of patients without smoking history was higher than that of patients with smoking history ( P<0.01). Patients with adenocarcinoma had a higher EGFR mutation rate than squamous cell carcinoma ( P = 0.002). The EGFR mutation rate in patients with stage Ⅰ-Ⅱwere higher than that in patents with stage Ⅲ-Ⅳ ( P = 0.013). The EGFR mutation rate in tissue samples were higher than that in peripheral blood samples ( P = 0.009). In 328 patients the EGFR single-point mutation rate was 24.70% (81/328), and the compound mutation rate was 15.85% (52/328); the common mutation rate was 17.07% (56/328), and the rare mutation rate was 23.48% (77/328). The top 5 mutation types were L858R (10.06%), G719X+S768I (7.32%), 19-Del (7.01%), G719X+L861Q (6.40%), and G719X (4.21%). In 133 patients with EGFR mutation, the proportion of patients with rare mutation [57.89% (77/133)] was higher than the proportion of patients with common mutation [42.11% (56/133)]. Conclusion:The EGFR mutation rates of female, adenocarcinoma, non-smoking and young NSCLC patients in Fuyuan area are high, and the rare mutation rate is high.