Review of drug utilization research based on real-world data / 药学实践与服务

In recent years, the rapid development of medical information technology has made it critical to analyze large-scale diagnosis and therapeutic data and extract rules based on real medical environment. This has become an essential approach for marketing evaluation and regulatory decision-making of drugs and devices both domestically and internationally. Real world study （RWS）, as a novel methodology for clinical evaluation of drugs in the field of drug utilization research （DUR）, have presented opportunities and challenges for observational studies in assessing actual efficacy or effectiveness. However, despite being a popular methodological approach among scholars in the field, there are still limitations and deficiencies when analyzing population medication characteristics in RWS. Systematic evaluation research methods have not yet been established, leading to inadequate generation of real-world evidence （RWE）. The research design, methodological pathways, evaluation indicators, confounding factors, and bias management involved in DUR based on real-world data （RWD） were reviewed in this artical with the intention of providing guidance for further exploration into DUR.

Design of assisted patient conveying and vibration damping system / 医疗卫生装备

Objective To design an assisted patient conveying and vibration damping system to solve the problems of operator fatigue and patient bump during casualty evacuation.Methods The assisted patient conveying and vibration damping system was composed of several conveying straps and a vibration damping mechanism.The conveying straps were made up of a waist strap,two shoulder straps,a chest strap,adhesive straps and joint components,and the joint components included adjusting buckles,big buckles,small buckles,connecting buckles and hook mechanisms;the vibration damping mechanism adopted the technical form of extension handle combined with vibration absorber,in which the extension handle was made of rigid material and the vibration absorber was equipped with a scissor guiding mechanism.Tests were carried out on the system to record the operating time of the operators and to analyze the system's vibration damping characteristics.Results The system developed extended the operating time of the stretcher conveyers while reduced the vibration during casualty transport,with a maximum vibration reduction of 71.73％.Conclusion The system developed gains advantages in low vibration and low workload,and can be used for casualty conveying in poor road conditions.[Chinese Medical Equipment Journal,2024,45(1):15-24]

Effects of sFRP3 overexpression on the activation and proliferation of murine cardiac fibroblasts / 安徽医科大学学报

Objective @#To explore the role of secreted frizzled ⁃related protein 3 ( sFRP3) , a regulator of the Wnt signaling pathway , in the activation and proliferation of murine cardiac fibroblasts ( CFs ) . @*Methods @#Neonatalmice aged 1 -3 days were obtained for surgical procedures to collect heart tissues. After digestion, CFs were isola.ted and cultured. Transforming growth factor-beta 1 (TGF-β1 ) stimulation was used to induce activation and prolif.eration in CF's after they adhered to the culture dish. Once the model was confirmed, experimental and controlgroups were transfected with sFRP3 overexpression plasmids and empty plasmids for 24 -48 hours. Expression lev.els of sFRP3, Periostin (POSTN), Type I collagen ( Collagen I ), and proliferating cell nuclear antigen ( PCNA) were assessed at the molecular level using Westerm blot and qR'T-PCR. Changes in cell proliferation capacitywere examined using M'TT, CCK-8, and EdU staining methods.@*Results@#In the TGF-β1-induced activation andproliferation model of CFs, compared to the control group, the model group exhibited decreased expression of sFRP3 protein and mRNA , while the expression of activation and proliferation-related proteins PCNA, POSTN, andCollagen I was upregulated. Furthermore, in CFs overexpressing sFRP3 through plasmid transfection, the proteinand mRNA expression of PCNA, POSTN, and Collagen I decreased compared to the empty vector group. MTTCCK-8, and EdU experiments indicated a significant decrease in the proliferative activity of CFs in the sFRP3 over0verexpression of sFRP3 markedly inhibits theexpression group compared to the empty vector group. @*Conclusion@#Overexpression of sFRP3 markedly inhibits theactivation and proliferation of CFs, suggesting that sFRP3 may be a key gene involved in the regulation of CF activation and proliferation.

Prevalence and influencing factors of depressive symptoms among primary and middle school students in Xihu District / 预防医学

Abstract@#Objective To investigate the prevalence and influencing factors of depressive symptoms among primary and middle school students in Xihu District, Hangzhou City, so as to provide insights into depression control among primary and middle school students. @*Methods@# Students were sampled from two primary schools, two junior high schools, two ordinary high schools and one vocational high school in Xihu District using a stratified cluster random sampling method from September to November, 2021. Participants' demographics, diet, exercise, sleep and campus bullying were collected using questionnaire surveys. The depressive symptoms were evaluated using the Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D), and factors affecting the depressive symptoms were identified among primary and middle school students using a multivariable logistic regression model.@* Results@# A total of 1 518 students were investigated, including 518 primary school students (34.12%), 363 junior high school students (23.91%), 463 ordinary high school students (30.50%) and 174 vocational high school students (11.46%). Of all participants, there were 805 males (53.03%). The prevalence of depressive symptoms was 38.87% among the participants, and was 36.10%, 42.42%, 42.33% and 30.46% among primary school, junior high school, ordinary high school and vocational high school students, respectively. The multivariable logistic regression analysis showed that gender (OR=1.601, 95%CI: 1.289-1.989), type of school (junior high school, OR=1.299, 95%CI: 0.974-1.734; ordinary high school, OR=1.351, 95%CI: 1.025-1.780; vocational high school, OR=0.862, 95%CI: 0.585-1.272), frequency of fresh vegetable intake (less than once daily, OR=0.454, 95%CI: 0.304-0.679; once and more daily, OR=0.359, 95%CI: 0.235-0.548), duration spent on the internet (0.5 to 1 h daily, OR=1.447, 95%CI: 1.044-2.006; 1 h and longer daily, OR=1.456, 95%CI: 1.072-1.978), sufficient sleep (OR=0.525, 95%CI: 0.371-0.744), suffering from campus bullying (OR=1.992, 95%CI: 1.491-2.661) were associated with the development of depressive symptoms. @*Conclusions@# The prevalence of depressive symptoms is high among primary and middle school students in Xihu District. Gender, type of school, dietary behaviors, sleep duration and campus bullying are factors affecting the development of depressive symptoms.

Bibliometric analysis of brucellosis by CiteSpace / 药学实践与服务

Objective To perform a visual bibliometric analysis of hot spots as well as areas of Brucella disease research by searching brucellosis related literature. Methods A thematic search was conducted in the web of science core set database using Brucella disease or brucellosis as keywords to retrieve literature between January 1985 and December 2021. CiteSpace was used to visualize the countries, institutions, authors, and keywords in the retrieved relevant literatures. Results A total of 4 495 eligible articles studies were included, with the United States being the most populous country and the University of Sao Paulo being the most influential. Jilin University and Shihezi University in Xinjiang, China were relatively influential in this field. For the key words analysis, the top 3 of high-frequency words were infection, diagnosis, abortion, and in the 12 clusters formed, the clusters formed by #1, #4 were larger and the research hotspot continued. Keywords in the last five years including human brucellosis, immunity, zoonotic disease, were highlighted. Conclusion Study analysis suggested that human brucellosis with zoonosis was a research hotspot, more scholars focused on the infectious route and other exposure risks of cattle as intermediate hosts, epidemiological studies on brucellosis or will be new trends.

Systematic evaluation of prehospital external hemostatic dressings / 军事医学

Objective To evaluate the effectiveness,safety and operability of different types of pre-hospital topical hemostatic dressings given the limited clinical evidence of pre-hospital topical hemostatic dressings so as to provide reference for the subsequent establishment of a comprehensive index system.Methods A systematic review method was used to sift through and summarize the evaluation indexes of zeolite,kaolin and chitosan.Results Fifteen studies were included,only one of which was randomized controlled trial(RCT)study,and the rest were descriptive studies,involving military and civilian subjects.All the three types of hemostatic dressings in the included studies had good haemostatic effects,but the amount of data was too limited to compare the haemostatic effects between different types.Except for zeolite wounds that were likely to be burned by exothermic heat,the other types caused few adverse reactions but with unclear operability.There was no data on stability and economy in the selected literature.Conclusion Considering the ideal hemostatic agent and the standard requirements of Chinese expert consensus,it is recommended that the indicators in follow-up studies include efficacy,safety,operability,stability and economy,and that preclinical animal studies be included to supplement related indicators.

Risk factors of death and construction of a survival prediction model in maintenance hemodialysis patients with corona virus disease 2019 / 中华肾脏病杂志

It was a retrospective cohort study. Eighty maintenance hemodialysis (MHD) patients with corona virus disease 2019 (COVID-19) were enrolled, among whom 48 patients survived and 32 died. The clinical data between the survival and death groups were compared. The Cox regression model was used to analyze the risk factors of death in MHD patients with COVID-19, and a survival prediction model was constructed. The results showed that age, lesion-cumulative number of lung segments, C-reactive protein, procalcitonin, serum ferritin, interleukin-6, D-dimer, serum phosphorus, and proportions of males, diabetes and hypoxemia in the death group were higher than those in the survival group (all P<0.05). Increased age ( HR=1.039, 95% CI 1.007-1.072, P=0.017), diabetes ( HR=2.688, 95% CI 1.018-6.991, P=0.046), increased C-reactive protein ( HR=1.006, 95% CI 1.001-1.011, P=0.012), and increased serum phosphorus ( HR=1.573, 95% CI 1.015-2.438, P=0.043) were independent influencing factors of death in MHD patients with COVID-19. The survival prediction model was established based on age, diabetes, C-reactive protein and blood phosphorus. The area under the receiver operating characteristic curve of the combined model for survival time at 7-day, 14-day, and 21-day were 0.751 (95% CI 0.690-0.811), 0.768 (95% CI 0.712-0.824), and 0.780 (95% CI 0.729-0.831), respectively. The concordance index of cross- validation as internal validation was 0.797 (95% CI 0.757-0.837). Increased age, diabetes, elevated C-reactive protein and elevated blood phosphorus are independent risk factors of COVID-19 death in MHD patients, and the survival prediction model built by those factors has good efficacy.

Comparison of treatment efficacy between endoscopic ultrasound-guided puncture sclerotherapy and laparoscopic decapitation decompression for renal cysts in the upper pole (with video) / 中华消化内镜杂志

To compare the efficacy, safety and economic cost of endoscopic ultrasound (EUS)-guided puncture sclerotherapy and laparoscopic decapitation decompression for the renal cysts in the upper pole, data of patients with renal cysts in the upper pole who received EUS-guided puncture sclerotherapy (the EUS group, n=9) or laparoscopic decapitation decompression (the laparoscopy group, n=16) in the Second Affiliated Hospital of Soochow University from January 2021 to August 2022 were analyzed retrospectively. The effective rate, operation time, intraoperative blood loss, incidence of complications, hospital stay and treatment cost of the EUS group and the laparoscopy group were compared. Results showed that the effective rate was comparable in the EUS group and laparoscopy group (9/9 VS 14/16, P=0.520). The operation time was shorter (29.8±4.8 min VS 70.1±11.1 min, t=10.207, P<0.001), intraoperative blood loss less (0 mL VS 26.1±5.9 mL, t=13.089, P<0.001), postoperative hospital stay shorter (3.5±0.7 days VS 5.4±2.0 days, t=2.663, P=0.014), and total cost lower (10 547.85±2 388.19 yuan VS 15 316.09±5 352.45 yuan, t=2.517, P=0.019) in the EUS group compared with those in the laparoscopy group. There was no significant difference in the total hospital stay (8.1±2.0 days VS 9.3±3.1 days, t=1.019, P=0.319) or operation cost (3 946.79±490.82 yuan VS 3 860.18±857.42 yuan, t=-0.277, P=0.784) between the EUS group and laparoscopy group. There was 1 case of puncture bleeding, 1 case of hematuria, and 1 case of lumbago in the laparoscopy group, while no complication occurred in the EUS group. In conclusion, it is preliminarily believed that EUS-guided puncture sclerotherapy for renal cysts in the upper pole has similar clinical effects with higher safety, shorter postoperative hospital stay and lower total hospitalization cost compared with those of laparoscopic decapitation decompression, which is worth of clinical promotion.

Correlation analysis of serum zonulin, ZO-1, TNF-α with severity of acute pancreatitis / 中国医师杂志

Objective:To analyze the correlation between the severity of acute pancreatitis (AP) and the levels of zonulin, zonula occludens protein-1 (ZO-1), tumor necrosis factor -α (TNF -α) in the peripheral blood of patients with acute pancreatitis (AP), and the value of predicting moderate and severe AP.Methods:The clinical data of 115 AP patients admitted to the Second Affiliated Hospital of Anhui Medical University from June 2020 to January 2022 were retrospectively analyzed. They were divided into mild group (69 cases) and moderate severe group (46 cases). The blood levels of zonulin, ZO-1, and TNF-α were measured for all patients on the 1st, 3rd, and 7th day after admission, and the results of the two group tests were compared. The correlation between zonulin, ZO-1, TNF -α and Acute Physiology and Chronic Health Evaluation Ⅱ (APACHE Ⅱ) scores on the 1st day was and the value of various indicators for predicting moderate to severe AP were analyzed.Results:The C-reactive protein (CRP) levels of AP patients in the moderate to severe group were higher than those in the mild group, and the difference was statistically significant (all P<0.05). The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group showed an upward trend on the 1st, 3rd, and 7th days after admission. The levels of zonulin, ZO-1, and TNF -α in AP patients in the moderate to severe group were higher than those in the mild group at the same time point, and the differences were statistically significant (all P<0.05). The APACHE Ⅱ score of AP patients on the first day of admission was positively correlated with the levels of zonulin, ZO-1, and TNF -α ( r=0.736, 0.552, 0.621, all P<0.05). Zonulin had the highest area under the curve (AUC) for predicting moderate to severe AP, at 0.892, with an optimal threshold of 2.075 pg/ml. Zonulin had the highest sensitivity, at 0.804, and ZO-1 had the highest specificity, at 0.926. Using zonulin ≥2.075 pg/ml, ZO-1≥399.4 ng/ml, and TNF -α≥40.88 pg/ml as thresholds; the sensitivity and specificity obtained from parallel experiments were 0.976 and 0.710, respectively; The sensitivity and specificity obtained from the series of experiments were 0.326 and 0.999, respectively. Conclusions:There is a correlation between the serum levels of zonulin, ZO-1, and TNF -α in AP patients and the severity of AP. Zonulin, ZO-1, and TNF -α have certain clinical value in predicting moderate to severe AP.

The application of restricted kinematic alignment in total knee arthroplasty / 中华骨科杂志

Objective:To investigate the feasibility and therapeutic effect of total knee arthroplasty (TKA) with cruciate-retaining (CR) prosthesis by using FEM-X1 femoral extramedullary positioning instrument based on the theory of restricted kinematic alignment (rKA).Methods:Thirty five cases who underwent total knee arthroplasty in Nanjing Drum Tower Hospital from November 2019 to December 2020 were retrospectively analyzed, including 7 males and 28 females with an average age of 71± 8 years (ranging from 55 to 85 years) Following the guidance of rKA alignment, the FEM-X1 femoral extramedullary positioning instrument was used for TKA with CR prosthesis. Before the operation, the full-length lower limb radiographs of both anteroposterior and lateral views were taken in a standing position for preoperative assessment of lateral distal femoral angle (LDFA), the medial proximal tibial angle (MPTA) and hip-knee-ankle angle (HKA). According to the principle of rKA alignment, the target LDFA, MPTA and HKA were calculated. The proximal end of tibia and distal end of femur were cut using extramedullary positioning instrument respectively. The posterior femoral condyle was cut according to the tibial plateau and mediolateral soft tissue tension. The prosthesis was installed after osteotomy. The release of collateral ligaments, PCL function, release of PCL, patellofemoral trajectory, release of patellofemoral support band, the amount of blood loss and time of operation were recorded. Postoperative LDFA, MPTA, HKA, and posterior slope angle of tibial prosthesis were measured on X-ray images. The Knee Society Score (KSS) was used for functional evaluation.Results:Thirty five cases of TKA with CR prosthesis following rKA alignment were successfully completed. The operation time was 100 (90, 110) min, and the blood loss was 100 (100, 200) ml. 30 of them were followed up for 12.5±0.7 months (ranging from 12 to 14 months). The pre-operative and post-operative LDFA were 1.0°(-2.0°, 4.0°), 0°(-2.0°, 2.0°), MPTA were -4.0°(-5.0°, -1.0°), -2.0°(-3.0°, -1.0°), HKA were -3.0°(-3.0°, -1.0°), -2.0°(-3.0°, -1.0°). There was no significant difference between the three angles before and after operation ( Z=-0.89, P=0.372; Z=1.87, P=0.061; Z=1.03, P=0.302). The average posterior tibial slope was 5°(3°, 7°). At the follow-up of one year, the KSS clinical score was 94(92, 97) and functional score was 80(70, 90) in 30 cases. During the operation, PCL was released in 1 case because of excessive tension; and lateral retinacular release was performed in 1 case because of poor patellofemoral track. Conclusion:ITKA with CR prosthesis by using the extramedullary positioning instrument on the theory of rKA alignment showed a good clinical outcome at a short follow up.

Role of NLRP3 in sepsis-associated encephalopathy and the relationship with pyroptosis in microglia of mice / 中华麻醉学杂志

Objective:To evaluate the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) in sepsis-associated encephalopathy (SAE) and the relationship with pyroptosis in microglia of mice.Methods:Twenty-four SPF healthy male C57BL/6J mice, aged 6-8 weeks, weighing 18-22 g, were divided into 3 groups ( n=6 each) using a random number table method: sham operation group (Sham group), SAE group and SAE plus an NLRP3 inhibitor MCC950 group (SAE+ MCC950 group). The mouse model of SAE was prepared by cecal ligation and puncture after anesthesia. MCC950 20 mg/kg was intraperitoneally injected at 1 h after developing the model in SAE+ MCC950 group, and the equal volume of normal saline was given instead in the other groups. Open field tests were conducted at 1 day after developing the model to record the number of rearing and time spent in the central area. Novel object recognition tests were conducted at 2-3 days after developing the model to record the recognition index. After the behavioral experiment on 3 day after developing the model, mice were sacrificed and hippocampal tissues were collected for determination of the expression of NLRP3 (by Western blot), count of cells co-expressing NLRP3 and microglia-specific ionized calcium-binding adaptor molecule 1 (Iba-1) (by immunofluorescence), activity of caspase-1, and contents of interleukin-1beta(IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Compared with Sham group, the number of rearing was significantly reduced, the time spent in the central area was shortened, the recognition index was decreased, the expression of NLRP3 was up-regulated, the count of NLRP3 + -Iba-1 + cells was increased, and the activity of caspase-1 and contents of IL-1β and IL-18 were increased in SAE and SAE+ MCC950 groups ( P<0.05). Compared with SAE group, the number of rearing was significantly increased, the time spent in the central area was prolonged, the recognition index was increased, the expression of NLRP3 was down-regulated, the count of NLRP3 + -Iba-1 + cells was decreased, and the activity of caspase-1 and contents of IL-1β and IL-18 were decreased in SAE+ MCC950 group ( P<0.05). Conclusions:NLRP3 is involved in the development of SAE, which may be related to the mediation in microglial pyroptosis in mice.

Caffeic acid phenethyl ester improves peritoneal dialysis-associated peritoneal fibrosis by alleviating oxidative stress injury through activating nuclear factor erythroid-2-related factor 2/heme oxygenase-1 pathway / 中华肾脏病杂志

Objective:To investigate whether caffeic acid phenethyl ester (CAPE) would improve peritoneal dialysis (PD)-associated peritoneal fibrosis by alleviating oxidative stress through activating nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into four groups by the random number table: control (CON) group (0.9% normal saline 20 ml/d intraperitoneal injection), CAPE group (0.9% normal saline 20 ml/d+CAPE 10 mg·kg -1·d -1 intraperitoneal injection), PD group [4.25% glucose peritoneal dialysis fluid (PDF) 20 ml/d intraperitoneal injection with lipopolysaccharide 0.6 mg/kg intraperitoneal injection at day 1, 3, 5 and 7], and PD+CAPE group (CAPE 10 mg·kg -1·d -1 intraperitoneal injection in addition to PD group), with 8 rats per group. On day 28, rats were euthanized after peritoneal equilibration test, and then the parietal peritoneum and omentum were collected for follow-up tests. To further investigate the mechanism, primary peritoneal mesothelial cells (PMCs) of rats were isolated and cultured. The PMCs were stimulated with 2.5% glucose PDF and added with 5 μmol/L CAPE intervention. The Nrf2 inhibitor (ML385) was used to identify whether CAPE protected PMCs from PDF by activating the Nrf2/HO-1 pathway. Histopathological staining was used to detect structural changes of the peritoneum, and immunohistochemical analysis was performed on cleaved caspase-3, Bax, α-smooth muscle actin (α-SMA), fibronectin (FN), and typeⅠ collagen (Col-Ⅰ) protein. Western blotting was used to detect the protein expression of α-SMA, FN, transforming growth factor-β1 (TGF-β1), HO-1 and nuclear Nrf2 (N-Nrf2). The apoptosis detection kit was used to detect apoptosis and flow cytometry was used to detect reactive oxygen species (ROS) in PMCs. The malondialdehyde (MDA) and superoxide dismutase (SOD) activity detection kit were used to detect MDA content and SOD activity. Cell immunofluorescence was used to analyze the protein expression of Nrf2 in PMCs. Results:Compared with the CON group, the PD group had thicker peritoneum, and the expression levels of cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰand MDA in peritoneum were significantly higher, while HO-1, N-Nrf2 protein expression and SOD activity were lower (all P<0.05). Compared with the PD group, the parietal peritoneum morphology of CAPE+PD group was improved, accompanied by reduced cleaved caspase-3, Bax, α-SMA, FN, Col-Ⅰ protein expression, and MDA content, while N-Nrf2, HO-1 protein expression, and SOD activity were higher (all P<0.05). Compared with the CON group, the PD group had significantly lower ultrafiltration volume and higher peritoneal permeability (both P<0.05). After CAPE intervention, the peritoneal transport function of the rats was significantly improved ( P<0.05). In cultured PMCs, PDF inhibited nuclear translocation of Nrf2 and protein expression of HO-1, and upregulated intracellular ROS level. In addition, PDF increased cell apoptosis and the protein expression levels of α-SMA, TGF-β1 and FN (all P<0.05). CAPE activated nuclear translocation of Nrf2, increased HO-1 protein expression, downregulated intracellular ROS level, and partially reversed PDF-induced cell apoptosis and epithelial- mesenchymal transition (all P<0.05). The protective effects of CAPE on PMCs were partially abolished by ML385 (all P<0.05). Conclusions:CAPE can reduce PD-induced PMCs apoptosis and epithelial-mesenchymal transition by attenuating oxidative stress, and significantly improve peritoneal fibrosis and ultrafiltration function. The beneficial effects of CAPE on peritoneum are related to activation of Nrf2/HO-1 pathway.

Effects of AR on proliferation and lipid synthesis of myocardial fibroblasts in high glucose environment / 中国药理学通报

Aim To explore the effect of androgen receptor AR on the proliferation and lipid synthesis of cardiac fibroblasts under high-glucose conditions and the possible molecular mechanism.Methods The hearts of neonatal rats were dissected for primary culture of cardiac fibroblasts. Then the growth status of CFs was observed under the inverted microscope, and the identification of CFs was performed by immunofluorescence staining using anti-vimentin. After cell adherence, the cells were divided into blank control group, high glucose model group, negative control group, and overexpressed AR group. The glucose concentration was 33.0 mmol·L-1 except that the blank control group was 5.5 mmol·L-1. After 24 hours of CFs culture, Western blot and RT-qPCR were used to detect the expression of AR, FASN, PCNA, cyclin D1, α-SMA, and collagen . Oil red O and CCK-8 were used to detect the changes in lipid synthesis and cell proliferation ability, respectively.Results Compared with the blank control group, the lipid synthesis and proliferation of CFs in the high glucose model group were enhanced. Western blot and RT-qPCR results showed that the expression of AR decreased, while the expression of fat lipid synthase(FASN), proliferation marker PCNA, cyclin D1 and fibrosis marker α-SMA and collagen increased. After AR overexpressed plasmid was transfected into the CFs treated by high glucose, AR overexpression markedly decreased the expression of FASN, PCNA, cyclin D1, α-SMA and collagen compared with the empty plasmid‐transfected group. Meanwhile, oil red O staining and CCK-8 results showed that the lipid synthesis and proliferation ability of the overexpressed AR group decreased compared with the empty vector group, respectively. Conclusions High glucose promotes the proliferation and lipid synthesis of cardiac fibroblasts. Besides, the mechanism may be related to the regulation of lipid synthesis regulated by AR.

Effects of DNMT3A on mouse cardiac fibroblast proliferation and migration under high glucose environment / 中国药理学通报

Aim To investigate the effect of DNA methyltransferase 3A (DNMT3A) on the proliferation and migration of cardiac fibroblasts (CFs) in C57 mice under high glucose environment. Methods The hearts of C57 mice were taken from 1 to 3 days. After cutting and digesting, CFs were extracted by differential adherance centrifugattion and observed under microscope. After cell attachment, the cells were cultured under low glucose (5.5 mmol • L

Analysis of factors associated with the influence of femoral stem anteversion after total hip arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To explore the related factors of femoral stem anteversion (FSA) after total hip arthroplasty (THA), so as to provide reference for clinical design of FSA before operation and reduce the risk of hip dislocation after arthroplasty.@*METHODS@#Ninty-three patients (103 hips) who underwent THA between October 2021 and September 2022 and met the selection criteria were selected as the study subjects. Among them, there were 48 males and 45 females with an average age of 58.5 years (range, 25-88 years). Body mass index was 18.00-37.84 kg/m 2, with an average of 24.92 kg/m 2. There were 51 cases (57 hips) of osteonecrosis of femoral head, 35 cases (39 hips) of hip osteoarthritis, and 7 cases (7 hips) of congenital hip dysplasia. Based on CT images, the following indicators were measured: preoperative femoral neck anteversion (FNA), preoperative femoral rotation angle (FRA), preoperative acetabular anteversion (AA), and preoperative combined anteversion (CA; the sum of preoperative FNA and AA); postoperative FSA and the change in femoral anteversion angle (the difference between postoperative FSA and preoperative FNA). Based on preoperative X-ray films, the following indicators were measured: femoral cortical thickness index (CTI) and canal flare index (CFI), the proximal femoral medullary cavity was classified according to Noble classification (champagne cup type, normal type, chimney type), neck-shaft angle (NSA), and femoral offset (FO). Pearson correlation analysis, one-way ANOVA, and Point-biserial correlation analysis were used to investigate the correlation between postoperative FSA, postoperative change in femoral anteversion angle, and patient diagnosis, proximal femoral medullary cavity anatomy type, gender, age, as well as preoperative FNA, FRA, AA, CA, NSA, FO, CTI, and CFI. FSA was used as the dependent variable and the independent variables that may be related to it were included for multiple linear regression analysis.@*RESULTS@#Based on CT image measurement, preoperative FNA was (15.96±10.01)°, FRA (3.36±10.87)°, AA (12.94±8.83)°, CA (28.9±12.6)°, postoperative FSA (16.18±11.01)°, and postoperative change in femoral anteversion angle was (0.22±9.98)°. Based on preoperative X-ray films measurements, the CTI was 0.586±0.081; the CFI was 4.135±1.125, with 23 hips classified as champagne cup type, 68 hips as normal type, and 12 hips as chimney type in the proximal femoral medullary cavity anatomy; NSA was (132.87±7.83)°; FO was (40.53±10.11) mm. There was no significant difference between preoperative FNA and postoperative FSA ( t=-0.227, P=0.821). Pearson correlation analysis showed that postoperative FSA was positively correlated with preoperative FNA, preoperative CA, postoperative change in femoral anteversion angle, and age ( P<0.05), while negatively correlated with preoperative FRA ( P<0.05). The postoperative change in femoral anteversion angle were positively correlated with preoperative FRA and postoperative FSA ( P<0.05), and negatively correlated with preoperative CA and FNA ( P<0.05). One-way ANOVA analysis showed that the above two indicators were not correlated with diagnosis and the proximal femoral medullary cavity anatomy type ( P>0.05). Multiple linear regression analysis showed a linear correlation between FSA and FNA, CA, age, and FRA ( F=10.998, P<0.001), and the best fit model was FSA=0.48×FNA-2.551.@*CONCLUSION@#The factors related to FSA after THA include patient's age, preoperative FNA, CA, FRA and postoperative femoral anteversion, of which preoperative FNA is the most closely related. When designing a surgical plan before surgery, attention should be paid to the patient's preoperative FNA, and if necessary, CT around the hip joint should be scanned to gain a detailed understanding of the proximal femoral anatomical structure.

The value of serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 in early assessment of acute pancreatitis / 中华急诊医学杂志

Objective:To investigate the early evaluation potential of serum levels of apolipoprotein B/apolipoprotein A1 (Apo B/A1), microtubule-associated protein 1-light chain 3 (MAP1-LC3) and intercellular adhesion molecule-1 (ICAM-1) in acute pancreatitis (AP) patients.Methods:A total of 413 AP patients who were treated at the Second Affiliated Hospital of Anhui Medical University between January 2019 and August 2020 were enrolled. Serum samples were collected from AP patients within 24 h of admission. Patients were divided into the non-severe acute pancreatitis (Non-SAP, n=315) and severe acute pancreatitis (SAP, n=98) groups according to the severity of the disease. Sixty healthy controls were recruited. The differences of serum Apo B/A1, MAP1-LC3 and ICAM-1 among the three groups were compared by one-way analysis of variance, and the correlation between Apo B/A1, MAP1-LC3 and ICAM-1 and the severity of AP was analyzed by Pearson correlation analysis. Sensitivity and specificity in assessing AP severity were predicted by receiver operating characteristic curve (ROC). Results:The early levels of Apo B/A1, MAP1-LC3 and ICAM-1 were all significantly higher for AP patients than for healthy controls ( P<0.05), and the levels of Apo B/A1, MAP1-LC3 and ICAM-1 in SAP patients were significantly higher than those in non-SAP patients[Apo B/A1: 2.21±1.40 vs. (0.96±0.34); MAP1-LC3: 0.92±0.29 vs. (0.48±0.24) ng/mL and ICAM-1: (235.57±54.50 ) vs. (120.28±61.69)ng/mL; P<0.05]. Pearson correlation analysis showed that levels of Apo B/A1, MAP1-LC3 and ICAM-1 were positively correlated with the first Ranson score after admission ( P<0.05), and ICAM-1 showed the highest degree of correlation with AP severity ( r=0.519). Areas under the receiver operating characteristic curve (AUROC) were 0.769 for Apo B/A1, 0.811 for MAP1-LC3, 0.828 for ICAM-1, and 0.938 for combined detection. Conclusions:Serum levels of Apo B/A1, MAP1-LC3 and ICAM-1 within 24 h after admission are significantly correlated with the severity of AP, which has clinical significance for early prediction of the severity of AP.

Changes in coronal spino-pelvis alignment in patients with developmental hip dysplasia / 中华骨科杂志

Objective:To investigate the changes in coronal spino-pelvis alignment in patients with developmental dysplasia of the hip (DDH) and effects of total hip arthroplasty on it.Methods:This study included 48 patients (6 males and 42 females) with DDH who underwent total hip arthroplasty from January 2009 to December 2019 at the Department of Orthopaedics, the PLA General Hospital. The average age of patients was 42.81±10.42 years (range, 22 to 61 years), whose follow-up time was 10.31±2.62 months (range, 3 to 18 months). Eleven cases underwent bilateral hip replacements and 37 cases underwent unilateral hip replacements, which included 13 hips in Crowe I, 7 hips in II, 4 hips in III, 35 hips in IV. The coronal spino-pelvic parameters were measured with all patients, including Cobb angle, coronal balance distance (CBD), sacral obliquity (SO), iliac obliquity (IO), hip obliquity (HO), L 5 obliquity (L 5O) and leg length. Results:The interobserver reliability of IO, SO, HO and L 5O in patients with DDH was 0.965, 0.875, 0.912 and 0.934. The interobserver reliability of IO, SO, HO and L 5O was 0.887, 0.889, 0.892 and 0.907. Thirty-three patients diagnosed with DDH had leg length discrepancy, which the incidence was 69% (33/48). The incidence of scoliosis of patients was 58% (28/48). The incidence of pelvic obliquity was 96% (46/48). The preoperative IO was 6.71°±4.62° and the postoperative IO was 3.52°±3.14°, the difference was statistically significant ( t=4.81, P<0.001). The preoperative SO was 6.38°±5.48° and the postoperative SO was 3.72°±3.38°, the difference was statistically significant ( t=3.91, P<0.001). The preoperative HO was 5.32°±5.83° and the postoperative HO was 3.71°±3.62°, the difference had not statistically significant ( t=1.85, P=0.071). The preoperative L 5O was 6.12°±5.46° and the postoperative L 5O was 4.33°±4.71°, the difference had statistically significant ( t=2.15, P=0.037). The preoperative Cobb angle was 11.05°±10.76° and the postoperative Cobb angle was 6.82°±7.76°, which had a statistically difference ( t=4.07, P=0.001). There is no significant difference of preoperative CBD and postoperative CBD, which was 14.22±10.64 mm vs. 13.73±12.58 mm ( t=0.24, P=0.821). Cobb angle was positively correlated with SO and IO ( r=0.61, P<0.001; r=0.57, P<0.001). Conclusion:Causes coronal pelvic obliquity in patients with DDH included leg length discrepancy and hip dislocation. Coronal pelvic obliquity can lead to compensatory scoliosis, which alters the overall coronal spino-pelvic alignment of patients with DDH. However, they can still maintain coronal balance. Total hip arthroplasty could improve the degree of coronal pelvic obliquity significantly and compensatory scoliosis in patients with DDH.

C-reactive protein to albumin ratio is an independent influencing factor of mortality in peritoneal dialysis patients / 中华肾脏病杂志

Objective:To investigate the association between C-reactive protein (CRP)/albumin (ALB) ratio (CAR) and mortality in peritoneal dialysis (PD) patients.Methods:Clinical data of 791 PD patients in the Second Affiliated Hospital of Soochow University from January 1, 2004 to December 31, 2019 were retrospectively collected. According to the baseline quartiles of CAR, patients were divided into three groups: low-level CAR group (CAR≤0.161 mg/g, n=264), medium-level CAR group (CAR 0.162-0.214 mg/g, n=263) and high-level CAR group (CAR≥0.215 mg/g, n=264). The clinical data among the three groups were compared. Follow-up was ended on March 31, 2020, or when the patients stopped PD due to death, shift to hemodialysis, renal transplantation or recovery of renal function. Kaplan-Meier survival curve, multivariate Cox proportional hazard model and Fine-Gray competing risk model were used to assess the relationship between CAR and all-cause mortality and cardiovascular and cerebrovascular mortality. The association between CAR, CRP, ALB, neutrophil to lymphocyte ratio (NLR), or platelet to lymphocyte ratio (PLR) and mortality in PD patients was compared by receiver-operating characteristic curve (ROC curve) analysis. Results:The age of the patients was (59.8±15.7) years old, and 447(56.5%) patients were males. 714(90.3%) patients had hypertension. 233(29.5%) patients had diabetes. 182(23.0%) patients had cardiovascular diseases. The median follow-up time was 55(31, 88) months. By the end of the follow-up, 236 deaths (29.8%) happened, and 95 patients (12.0%) died from cardiovascular and cerebrovascular diseases. Kaplan-Meier survival analysis results showed that the overall survival rate of the high-level CAR group was lower than those of the low-level CAR group and medium-level CAR group (Log-rank test χ2=109.50, P<0.001). Multivariate Cox regression analysis and Fine-Gray competing risk model revealed that CAR was independently correlated with all-cause mortality and cardiovascular and cerebrovascular mortality after adjusting for confounding factors ( HR=2.891, 95% CI 1.921-4.351, P<0.001; SHR=1.297, 95% CI 1.128-1.490, P<0.001). ROC curve analysis results showed that the area under the curve ( AUC) of CAR for predicting the risk of all-cause mortality in PD patients was 0.737(95% CI 0.700-0.774), which was superior to those of CRP ( AUC=0.643, 95% CI 0.599-0.687), NLR( AUC=0.608, 95% CI 0.563-0.653) and PLR ( AUC=0.554, 95% CI 0.508-0.601), and slightly lower than ALB ( AUC=0.752, 95% CI 0.716-0.788). The optimal cutoff value of CAR for death was 0.19 mg/g, with the sensitivity and specificity of 70.8% and 68.3%, respectively. Conclusions:Increasing CAR level is an independent risk factor of all-cause mortality and cardiovascular and cerebrovascular mortality in PD patients, and its correlation with mortality is higher than those of inflammatory parameters such as CRP, NLR and PLR.

Adaptive phenotypes of Yersinia pestis induced by successive passages in macrophages / 中华微生物学和免疫学杂志

Objective:To investigate the changes in adaptive phenotypes of Yersinia pestis ( Yp) during successive passages in macrophages. Methods:A Yp strain of 201-MI was induced by 50 successive passages of Yp 201 strain in Raw264.7 cells. Phenotypic characteristics of 201 and 201-MI strains were compared by analyzing their survival rates in macrophages, growth curves, biofilm formation abilities, acid and hydrogen peroxide-stress tolerance, and virulence to mammal cells (Raw264.7 and HeLa cells) and mice. Results:Comparing with 201 strain, 201-MI strain showed various phenotypic changes, including higher survival rate in Raw264.7 cells, faster growth in iron-deficient medium, higher tolerance to acid and hydrogen peroxide, decreased biofilm formation ability, and less damages to Raw264.7 and HeLa cells. More-over, 201-MI strain showed decreased virulence to mice in both subcutaneous and intraperitoneal challenges. Preliminary comparative genomics analysis revealed some indel and nonsense mutations in 201-MI strain, which might account for its phenotype changes.Conclusions:After successive passages in macrophages, Yp showed some phenotypic changes, which might reflect its adaptive evolution under the pressure of macrophages. Detailed multi-omics analysis would be of great help to understand the underlying genetic mechanisms of these changes, and the related Yp-macrophage interaction processes as well.

Effects of ALKBH5 regulation on proliferation of cardiac fibroblasts in rats / 安徽医科大学学报

Objective @#To investigate the role of N-methyladenosine(m6 A) demethylase ALKBH5 in the prolifera- tion and activation of cardiac fibroblasts( CFs) in rats．@*Methods @#The CFs taken from SD rats in 1 to 3 days were isolated by differential adhesion and observed under microscope．After cells were adherently grown to appropriate density，the cells were induced by TGF-β1 for modeling．The model cells were divided into the overexpression of ALKBH5 group infected by lentivirus and the negative control group for 24－48 hours. RT-qPCR was used to detect mRNA expression of ALKBH5，α-smooth muscle actin( α-SMA) ，type I collagen ( Collagen Ⅰ ) and proliferating cell nuclear antigen (PCNA) ．The expression of ALKBH5、α-SMA、Collagen Ⅰ and PCNA were assayed by West- ern blot．The cell proliferation activity was tested by CCK-8 assay and EdU. @*Results @#Compared with the control group，the protein and mRNA of ALKBH5 were reduced in the model group active by TGF-β1．Meanwhile，the bi- omarkers of activation，such as PCNA，α-SMA and Collagen Ⅰ , increased significantly．Besides，the protein and mRNA of PCNA、α-SMA and Collagen Ⅰ were lower in overexpression of ALKBH5 group than those of the negative control group．CCK-8 assay and EdU suggested that the proliferation viability of CFs was reduced evidently in over- expression of ALKBH5 group，compared with the negative control group．@*Conclusion @#Overexpression of ALKBH5 can inhibit the proliferation of CFs，suggesting that ALKBH5 may be a key regulatory point in the development of myocardial fibrosis.