OBJECTIVE To develop evidence-based clinical practice recommendations for the use of hemostatic drugs in special populations， so as to improve the efficacy and safety of medication.METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital， a working group of 79 experts covering clinical pharmacy， obstetrics and gynecology， pediatrics and other fields was established. Clinical questions regarding the efficacy and safety of hemostatic drugs in special populations were screened through literature review and two rounds of Delphi questionnaire surveys. Intervention questions were structured using the population， intervention， comparison， and outcome framework， while management questions were additionally described using the population， clinical setting, management measure， and outcome framework. Databases including Medline， Embase， Cochrane Library， CNKI， Wanfang Data， and VIP were systematically searched to collect and screen relevant evidence. Recommendations were formulated through recommendation questionnaire surveys and expert consensus meetings， and the quality of evidence and strength of recommendations were graded according to the Grading of Recommendations Assessment， Development and Evaluation system. RESULTS &CONCLUSIONS A total of 8 clinical questions were finally determined， the consensus rates of all clinical questions and recommendations were more than 90%， and 8 recommendations on the use of hemostatic drugs in special populations were formulated. These recommendations cover special populations including children， women during pregnancy/puerperium/lactation， the elderly， patients with hepatic impairment， patients in the perioperative period of liver transplantation， patients with renal impairment/on dialysis/in the perioperative period of kidney transplantation， immunocompromised patients， and patients with hematological diseases. The recommendations specify the applicable scenarios， dose adjustment principles， monitoring indicators， and safety management strategies of hemostatic drugs in different special populations， which can provide a reference for the clinical application of hemostatic drugs in special populations and help clinicians and pharmacists develop individualized medication plans.

Objective:To investigate the clinical characteristics and management status of children with Turner syndrome (TS) in China.Methods:As a cross-sectional study, 1 089 TS patients were included in the database of the National Collaborative Alliance for the Diagnosis and Treatment of Turner Syndrome from August 2019 to November 2023. Clinical characteristics (growth development, sexual development, organ anomalies, etc.), karyotypes, auxiliary examinations, and treatments were collected and analyzed.Results:Among the 1 089 TS cases, 809 were recorded karyotypes. The karyotype distribution was as follows: 45, X in 317 cases (39.2%), X chromosome structural variants (including partial deletions of p or q arm, ring chromosome, and marker chromosome) in 89 cases (11.0%), 45, X/46, XX mosaicism in 158 cases (19.5%), mosaicism with X chromosome structural variants in 209 cases (25.8%), and presence of Y chromosome material in 36 cases (4.4%). Among the 824 TS cases, the age of diagnosis was 9.7(6.4, 12.2) years, with a height standard deviation score (HtSDS) of -3.1±1.2. Five hundred and fifty three cases underwent growth hormone (GH) stimulation test, and 352 cases (63.7%) had GH peak values <10 μg/L and 75.9% (577/760) had low IGF1 levels, with IGF1 SDS ≤-2 accounting for 38.2% (290 cases). Among 471 cases aged ≥8 years, 132 cases (28.0%) showed spontaneous sexual development (mean bone age (11.0±1.7) years), 10 cases had spontaneous menarche (mean bone age (12.0±2.2) years), and 2 cases had regular menstrual cycles. Common physical features included cubitus valgus (311 cases (28.5%)), neck webbing (188 cases (17.2%)), low posterior hairline (185 cases (17.0%)), shield chest (153 cases (14.0%)), high arched palate (127 cases (11.6%)), short fourth metacarpal (43 cases (3.9%)), and spinal abnormalities (38 cases (3.5%)). Congenital cardiovascular and urogenital anomalies occurred in 91 cases (19.4%) and 66 cases (12.0%)respectively. Abdominal ultrasound in 33 cases (7.2%) indicated fatty liver, hepatomegaly, intrahepatic bile duct stones, and splenomegaly. Among 23 cases undergoing oral glucose tolerance test (OGTT) test, 2 were diagnosed with diabetes mellitus and 4 with impaired glucose tolerance. Following diagnosis, 669 cases (80.7%) received rhGH treatment at a chronological age of (9±4) years and bone age of (8.3±3.2) years. Additionally, 112 cases (19.4%) received sex hormone replacement therapy starting at the age of (14±4) years and bone age of (12.6±1.2) years.Conclusions:The karyotypes of 45, X and mosaicism were most common in Chinese children with TS. The clinical manifestations were mainly short stature and gonadal dysplasia. However, a few TS children could be in the normal range of height, and some cases among those aged of ≥8 years old had spontaneous sexual development. Some exhibited physical features, congenital cardiovascular and urogenital anomalies, and dysfunction of the hypothalamic-pituitary-IGF1 axis. Moreover, a few of them developed impaired glucose tolerance and diabetes mellitus. Following diagnosis, most of the patients received rhGH treatment, and a few of them received sex hormone replacement therapy.

Aim To systematically evaluate the efficacy and safety of Tongxinluo capsule combined with rosuvas-tatin in the treatment of carotid atherosclerosis.Methods A comprehensive screening of Tongxinluo capsule combined with rosuvastatin was performed by Web searching the CNKI,Wanfang Data,VIP,PubMed,Embase,The Cochrane Li-brary,and Web of Science from the construction of the database to August 31,2023,to comprehensively screen the litera-ture of randomized controlled studies of Tongxinluo capsule combined with rosuvastatin in the treatment of carotid athero-sclerosis in the literature of randomized controlled studies,and Meta-analysis was performed using RevMan 5.4 software.Results A total of 8 studies were included with 858 total cases,426 in the treatment group and 432 in the control group.Meta-analysis showed that the addition of Tongxinluo capsule to rosuvastatin treatment lowered total cholesterol(MD=-0.54,95％CI:-0.61～-0.46,P＜0.00001),triglyceride(MD=-0.28,95％CI:-0.37～-0.20,P＜0.00001),low density lipoprotein cholesterol(MD=-0.35,95％CI:-0.42～-0.29,P＜0.00001)and increased high density lipoprotein cholesterol(MD=0.27,95％CI:0.05～0.50,P=0.02)levels,lowered carotid intima-media thickness(MD=-0.35,95％CI:-0.48～-0.22,P＜0.00001)and plaque Crouse's score(MD=-1.33,95％CI:-2.11～-0.55,P=0.0009),and the differences were statistically significant(P＜0.05).Adverse effects were reported in five studies,and the difference was not statistically significant(MD=1.80,95％CI:0.80～4.08,P=0.16).Conclusion Tongxinluo capsule combined with rosuvastatin in the treatment of carotid atherosclerosis can improve the blood lipid level and reduce the degree of atherosclerosis,with better efficacy and safety,which can be further promoted for clinical use.

Aim To systematically evaluate the efficacy and safety of Tongxinluo capsule combined with rosuvas-tatin in the treatment of carotid atherosclerosis.Methods A comprehensive screening of Tongxinluo capsule combined with rosuvastatin was performed by Web searching the CNKI,Wanfang Data,VIP,PubMed,Embase,The Cochrane Li-brary,and Web of Science from the construction of the database to August 31,2023,to comprehensively screen the litera-ture of randomized controlled studies of Tongxinluo capsule combined with rosuvastatin in the treatment of carotid athero-sclerosis in the literature of randomized controlled studies,and Meta-analysis was performed using RevMan 5.4 software.Results A total of 8 studies were included with 858 total cases,426 in the treatment group and 432 in the control group.Meta-analysis showed that the addition of Tongxinluo capsule to rosuvastatin treatment lowered total cholesterol(MD=-0.54,95％CI:-0.61～-0.46,P＜0.00001),triglyceride(MD=-0.28,95％CI:-0.37～-0.20,P＜0.00001),low density lipoprotein cholesterol(MD=-0.35,95％CI:-0.42～-0.29,P＜0.00001)and increased high density lipoprotein cholesterol(MD=0.27,95％CI:0.05～0.50,P=0.02)levels,lowered carotid intima-media thickness(MD=-0.35,95％CI:-0.48～-0.22,P＜0.00001)and plaque Crouse's score(MD=-1.33,95％CI:-2.11～-0.55,P=0.0009),and the differences were statistically significant(P＜0.05).Adverse effects were reported in five studies,and the difference was not statistically significant(MD=1.80,95％CI:0.80～4.08,P=0.16).Conclusion Tongxinluo capsule combined with rosuvastatin in the treatment of carotid atherosclerosis can improve the blood lipid level and reduce the degree of atherosclerosis,with better efficacy and safety,which can be further promoted for clinical use.

Background In view of circulatory diseases, most previous studies focused on the impacts of air pollution and meteorological factors, while ignoring the influence of built environment. Objective To investigate and quantify the impact of built environment on circulatory diseases in China. Methods Circulatory disease mortality data and built environment data (including urban greenery coverage, urban land use, urban land use mix, urban road facilities and urban medical facilities) of 17 cities in China from 2000 to 2019 were collected. Multiple linear regression was used to analyze which built environment elements had significant influence on circulatory diseases, and to quantify their effects. Furthermore, the changes of built environment indicators on circulatory disease mortality were evaluated under different levels of urban economic development and various air quality. Results The built environment affected the mortality of circulatory diseases during the study period (P<0.05). Urban green space and commercial land area were negatively correlated with circulatory disease mortality, and regression coefficients were −0.550 and −0.280, respectively (P<0.05). On the contrary, the increase of urban road area, residential land ratio, and the degree of land use mix were positively associated with circulatory disease mortality, and their regression coefficients were 0.322, 0.283, and 0.176, respectively (P<0.05). When the level of urban economic development was low, the impact of commercial land use ratio on circulatory diseases was stronger, and the regression coefficient was −0.476 (P<0.05). When urban air pollution worsened, the impacts of per capita green coverage area and per capita urban road area on the disease were more prominent, and the regression coefficients were −0.528 and 0.372, respectively (P<0.05). Conclusion There is a significant correlation between urban built environment and mortality of circulatory diseases. To be specific, circulatory disease mortality has a negative correlation with per capita green coverage area and commercial land use ratio, and a positive correlation with per capita urban road area, residential land ratio and degree of land use mix.

BACKGROUND: With the extensive development of minimally invasive surgery for pulmonary nodules, preoperative localization becomes more and more critical. There are some defects in traditional localization methods, so it is necessary to improve. The aim of this study was to compare and analyze the safety and effectiveness of two new methods, namely four-hook needle and memory alloy coil, in the localization of pulmonary nodules. METHODS: A retrospective analysis of 152 patients was performed. 76 cases were in four-hook needle group, and 76 cases were in memory alloy coil group. Pulmonary nodules were located before operation, and then video-assisted wedge resection was performed. The average procedure time, localization complications and nodule resection time were counted. RESULTS: The target pulmonary nodules were successfully removed in both groups. In four-hook needle group, 76 patients found localization devices, all the pulmonary nodules were successfully removed, and one case was transferred to open the chest for wedge resection of pulmonary nodules due to severe thoracic adhesion. All 76 patients in memory alloy coil group were successfully resected with pulmonary nodules, and one patient underwent compromising enlarged resection because no lesion was found after the specimen was removed during the operation. There was no significant difference in the incidence of pneumothorax and pulmonary hemorrhage, the success rate of localization and nodule wedge resection time between the two groups. The average time of localization in four-hook needle group was (13.66±3.11) min, lower than that of memory alloy coil group (15.51±3.65) min, and the difference was statistically significant (P=0.001). In memory alloy coil group, when the distance from the nodule to the pleura was ≥1.5 cm and <1.5 cm, the average localization time was (17.20±4.46) min and (14.91±3.15) min, respectively, and there was a statistical difference between the two distance (P=0.044). CONCLUSIONS Four-hook needle and memory alloy coil have good safety and effectiveness, and the localization time of four-hook needle is shorter. When using memory alloy coil, the effect of the method is better for pulmonary nodules with a distance less than 1.5 cm to pleura.
Alloys ; Humans ; Lung Neoplasms/surgery* ; Multiple Pulmonary Nodules ; Retrospective Studies ; Thoracic Surgery, Video-Assisted ; Tomography, X-Ray Computed

To construct TeI3c/4c-based and temperature-inducible gene inactivation system (Thermotargetron) and to apply it to gene inactivation of mesophilic bacteria. The subunit of flagellum (fliC) and C4 dicarboxylate orotate:H⁺ symporter (dctA) genes were chosen as targets in the genome of Escherichia coli HMS174 (DE3) strain. According to recognition roles of TeI3c/4c intron, the fliC489a, fliC828s, fliC1038s and dctA2a sites were chosen as target sites. Gene-targeting plasmids were constructed based on pHK-TT1A by using overlap PCR method and transformed into HMS174 cells. An aliquot mid-log phase cultures of the transformants were shocked at 48 °C and plated on LB plate (containing chloramphenicol). Afterwards, gene mutants were screened by using colony PCR and DNA sequencing. After the mutants were obtained, the phenotypes of ΔfliC and ΔdctA gene mutants were characterized by using agar puncture and carbon metabolism experiments. Colony PCR and sequencing results show that TeI3c/4c intron was inserted in the designed sites of fliC and dctA genes. The gene-targeting efficiency of Thermotargetron system was 100%. Phenotype verification experiments of the mutants demonstrated that the cell motility of all ΔfliC mutants was damaged and the malate assimilation ability of ΔdctA mutant was deprived comparing to wild-type HMS174 strain. In our study, a temperature-inducible and high-efficiency gene inactivation system was established for mesophilic bacteria. This system could achieve high efficiency and precise gene inactivation by modulation of the incubation duration of the transformants at 48 °C.

Background and objective hTe signiifcant effcacy of tyrosine kinase inhibitors (TKIs) has been ap-proved for advanced non-small cell lung cancer (NSCLC) patients with activating epidermal growth factor receptor (EGFR) mutations. No clear evidence exists that EGFR-L861Q is sensitive to TKIs, and the best treatment for NSCLC patients with EGFR-L861Q mutation is undetermined. hTis study aims to discuss the best treatment for advanced NSCLC patients with EG-FR-L861Q mutation by analyzing the differences among the structures of wild-type EGFR, activating mutant EGFR-L858R, and EGFR-L861Q mutation. Method The protein structures of wild-type EGFR were reconstructed. EGFR-L858R and EGFR-L861Q mutation were activated. hTe differences among the three kinds of protein conformation were analyzed using homologous modeling technique. Results hTe structure of EGFR-L858R and wild-type EGFR exhibited notable distinctions. hTe structure of EGFR-L861Q mutation was different compared with wild-type EGFR and activating mutant EGFR-L858R protein conformations. NSCLC patients with EGFR-L861Q mutation were given chemotherapy as the ifrst-line of therapy, and TKIs were applied to maintain treatment when the tumor is unchanged. Effect evaluation result was improved when the lung computed tomography lesions were reviewed. Conclusion hTe analysis of the protein conformation of EGFR-L861Q muta-tion and the curative effect of chemotherapy with TKIs could help predict the sensitivity of EGFR-L861Q to TKIs. Combining the analysis with a clinical case, maintenance treatment with TKIs may achieve satisfactory curative effect in advanced NSCLC patients who have achieved disease control atfer ifrst-line chemotherapy.

Objective Cloning and expression of Par6A.Methods Par6A cDNA was amplified from rat L6 skeletal muscle cells by RT-PCR and the cloning and expression vectors of Par6A were constructed.The expression vector was transfected into 293 cells.Furthermore,the function of Par6A was confirmed by Co-immunoprecipitation.Results Par6A cDNA with approximately 1 kb in length was successfully amplified,and the expression vector of pDsRed-Express-N1-Par6A was constructed.The red fluorescene was seen under fluorescent microscope after 293ET cells were transfected for 24 h using the pDsRed-Express-N1-Par6A vector.The expressed Par6A protein can interacte with PKC?.Conclusion We successfully cloned the Par6A cDNA from rat L6 skeletal muscle cells,which provided a reliable method to study the function of Par6A.