Aim To investigate the effects of 2-dode-cyl-6-methoxycyclohexa-2 , 5-diene-l, 4-dione ( DM-DD) on resisting hepatic fibrosis induced by carbon tetrachloride ( CC14 ) in rats and the underlying mechanisms , with a specific focus on the TGF-pi/Smads signaling pathway. Methods The hepatic fibrosis model was replicated using 50% CC14. Various parameters, including levels of aspartate transferase ( AST) , ala-nine transferase ( ALT ) , albumin/globulin ( A/G ) , total protein (TP) , total bilirubin (T-BIL) , hyaluron-ic acid ( HA ) , laminin ( LN ) , collagen type Ж ( Col Ж) , and collagen type IV(ColIV) in the blood, were measured. Liver tissue lesions and fiber formation were observed using HE and Masson staining. The expression levels of a smooth muscle actin (a-SMA) , collagen type I ( Col I ) , transformed growth factor (TGF-pi), Smad2, and Smad7 proteins were assessed using immunohistochemistry. a-SMA, Coll, TGF-pi, and Smad7 mRNA levels in liver tissue were measured by RT-PCR. Additionally, the expression levels of TGF-pi, Smad4, and Smad7 proteins in liver tissue were determined by Western blot. Results In comparison to the normal control group, the model group exhibited significantly elevated levels of AST, ALT, TP, T-BIL, HA, LN, Col Ш and Col IV in serum. But A/G level notably decreased. Successful modeling was confirmed by the presence of extensive fiber formations observed through HE and Massonstaining in liver tissue. The DMDD administration group demonstrated a notable decrease levels of AST, ALT, TP, T-BIL, HA, LN, Col III, and CollV, but A/G was significantly elevated when compared to the model group. Furthermore, a-SMA, Coll, TGF-f31, Smad2 and Smad4 mRNA and protein levels in the DMDD administration group were significantly reduced, while Smad7 significantly declined. HE and Masson staining results reflected a marked reduction in fibrous hyper-plasia. Conclusion DMDD exhibits a protective effect against CCl4-induced hepatic fibrosis, and its mechanism appears to be associated with the TGF-fJl/ Smads signaling pathway.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

Objective:To establish a new classification system for distal clavicle fracture and evaluate its clinical effectiveness.Methods:A retrospective case series study was conducted to analyze the clinical data of 101 patients with distal clavicle fracture admitted to First Affiliated Hospital of Nanjing Medical University from January 2015 to March 2022, including 57 males and 44 females, aged 19-86 years [(53.8±14.0)years]. Before treatment, patients were routinely subjected to bilateral anteroposterior radiography of the shoulder joints to measure the length of the fractured fragments, coracoclavicular distance, and acromioclavicular distance. According to the correlation between the location of the fracture line and the insertion of the coracoclavicular ligament, distal clavicle fracture was divided into three types: type I, with the fracture line lateral to the coracoclavicular ligament region; type II, with the fracture line in the coracoclavicular ligament region; type III, with the fracture line medial to the coracoclavicular ligament region. According to the injury severity of the coracoclavicular ligament and acromioclavicular ligament, type I was further subdivided into type IA, IB, IC and ID, and type II fracture was further subdivided into type IIA, IIB, IIC, IID and IIE. All the 101 patients were classified and randomly reclassified at an interval of 3 months by 10 senior and 10 junior shoulder surgeons according to the new classification method. Kappa coefficients were used to evaluate the inter- and intra-observer consistency of the new classification. Fifty-two patients with stable fracture (types IA, IB, IIC, and IID) were treated non-surgically, while 49 patients with unstable fracture (types IC, ID, IIA, IIB, IIE, and III) were treated surgically, including 26 patients with anatomic coracoclavicular ligament reconstruction, 9 with locking plate fixation, 8 with clavicle hook plate fixation, 4 with anatomic coracoclavicular ligament reconstruction combined with locking plate fixation, and 2 with anatomic coracoclavicular ligament reconstruction combined with tension screw fixation. The patients were assessed using the visual analogue scale (VAS) and Constant-Murley shoulder score before treatment and at 3, 6, 12, and 18 months after treatment. The coracoclavicular distance and acromioclavicular distance on the anteroposterior radiographs of the healthy and affected shoulder joints were measured at 3, 6, 12, and 18 months after treatment, and fracture healing time and complications were observed.Results:The length of the fractured fragments was 12.9 (9.7, 17.6)mm in patients with type I fracture, 24.7 (21.8, 27.8)mm in patients with type II fracture, and 43.6 (41.2, 46.9)mm in patients with type III fracture ( P<0.01). There were no significant differences in the coracoclavicular distance and acromioclavicular distance of the affected and healthy shoulders among the patients with types IA, IB, IIC, IID, and III fracture ( P>0.05); For the patients with types IC, IIA, IIB and IIE fracture, the coracoclavicular distance of the affected shoulder was significantly increased compared with that of the healthy shoulder ( P<0.01), while there was no significant difference in the acromioclavicular distance of the affected and healthy shoulders ( P>0.05). Both of the inter- and intra-observer consistency of the new classification was good. The inter- and intra-observer Kappa values were 0.69 and 0.71 respectively among the senior shoulder surgeons, and 0.61 and 0.64 respectively among the junior shoulder surgeons. All the patients were followed up for 18-104 months [28(23, 32)months]. At 3, 6, 12 and 18 months after treatment, the VAS scores of non-surgical patients were 3(2, 3)points, 2(1, 2)points, 1(0, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 6)points before treatment ( P<0.01); the VAS scores of surgical patients were 3(2, 3)points, 2(1, 2)points, 1(1, 1)points and 0(0, 1)points respectively, significantly decreased compared with 6(5, 7)points before treatment ( P<0.01); the Constant-Murley shoulder scores of non-surgical patients were (76.6±5.3)points, (84.3±5.0)points, (88.4±4.0)points and (91.9±3.8)points respectively, significantly higher than (42.7±5.2)points before treatment ( P<0.01); the Constant-Murley shoulder scores of surgical patients were (77.4±4.6)points, (84.4±4.7)points, (87.6±3.7)points and (91.7±4.0)points respectively, significantly higher than (42.8±5.3)points before treatment ( P<0.01). At 3, 6, 12 and 18 months after treatment, the coracoclavicular distance of the affected shoulder in non-surgical patients was not significantly different from that before treatment ( P>0.05), while the acromioclavicular distance of the affected shoulder in surgical patients was significantly reduced compared with that before treatment ( P<0.01). There were no significant differences in the coracoclavicular distance of the healthy shoulder or bilateral acromioclavicular distance in non-surgical and surgical patients at 3, 6, 12, and 18 months after treatment compared with those before treatment ( P>0.05). Fractures were healed within 12 months after treatment in all the patients, without dislocation or subluxation of the acromioclavicular joint, internal fixation failure or internal fixator breakage. Eight patients treated with clavicular hook plate fixation had shoulder pain associated with limited mobility after operation, and all underwent a second operation to remove the clavicular hook plate at 12 months after operation. Conclusions:The new classification system for distal clavicle fracture is established, which comprehensively considers the position of the fracture line, injury of the coracoclavicular and acromioclavicular ligaments, and fracture stability. The new classification system exhibits good inter- and intra- observer consistency, and the effectiveness of its preliminary clinical application is satisfactory.

Ferroptosis is a new type of programmed cell death different from apoptosis and necrosis.Its mechanism involves iron overload,lipid peroxidation,and reactive oxygen species(ROS)generation caused by disordered iron metabolism.Ferroptosis is associated with primary osteoporosis as well as the secondary osteoporosis such as steroid-induced osteoporosis,diabetic osteoporosis and postmenopausal osteoporosis.The Chinese medicines for the prevention and treatment of osteoporosis through the mechanism of ferroptosis mainly involve Chinese herbal compounds such as herbal pair of Eucommiae Cortex-Dipsaci Radix,Jintiange Capsules,and Bugu Shengsui Prescription,the single Chinese herbal medicine of Achyranthis Bidentatae Radix,and the active ingredients of herbal medicines such as icariin,gastrodin,quercetin,and artesunate.The prevention and treatment of osteoporosis by Chinese medicine monomer and Chinese herbal compound can inhibit ferroptosis through multiple targets and multiple pathways.At present,Chinese medicine has advantages in the prevention and treatment of postmenopausal osteoporosis.The prevention and treatment of osteoporosis by regulating the mechanism of ferroptosis can provide a direction for the future research on the prevention and treatment of osteoporosis by Chinese medicine.

Based on the practice of intelligent construction of medical education in Fuwai Hospital of CAMS&PUMC in recent years,this article deeply discusses the important role of R & D management thinking of integrated product development(Integrated Product Development,IPD)in the intelligent construction of hospital education.By building an intelligent platform for medical education,we can help hospitals improve their teaching strength in an all-round way,provide strong technical support for the performance evaluation of third-tier public hospitals,greatly improve the operational efficiency of hospitals,and firmly grasp the pulse of the times.to provide new solutions for the construction of hospital education intelligence system.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.

OBJECTIVE: This study aimed to investigate the association between fruit and vegetable intake and arterial stiffness. METHODS: We conducted a cohort-based study comprising 6,628 participants with arterial stiffness information in the Prediction for Atherosclerotic Cardiovascular Disease Risk in China (China-PAR) project. A semi-quantitative food-frequency questionnaire was used to assess baseline (2007-2008) and recent (2018-2021) fruit and vegetable intake. We assessed changes in fruit and vegetable intake from 2007-2008 to 2018-2021 in 6,481 participants. Arterial stiffness was measured using the arterial velocity-pulse index (AVI) and arterial pressure-volume index (API). Elevated AVI and API values were defined according to diverse age reference ranges. RESULTS: Multivariable-adjusted linear regression models revealed that every 100 g/d increment in fruit and vegetable intake was associated with a 0.11 decrease in AVI ( B= -0.11; 95% confidence interval [ CI]: -0.20, -0.02) on average, rather than API ( B = 0.02; 95% CI: -0.09, 0.13). The risk of elevated AVI (odds ratio [ OR] = 0.82; 95% CI: 0.70, 0.97) is 18% lower in individuals with high intake (≥ 500 g/d) than in those with low intake (< 500 g/d). Furthermore, maintaining a high intake in the past median of 11.5 years of follow-up was associated with an even lower risk of elevated AVI compared with a low intake at both baseline and follow-up ( OR = 0.64; 95% CI: 0.49, 0.83). CONCLUSION Fruit and vegetable intake was negatively associated with arterial stiffness, emphasizing recommendations for adherence to fruit and vegetable intake for the prevention of arterial stiffness.
Humans ; Vascular Stiffness ; Fruit ; Vegetables ; Atherosclerosis ; China

BACKGROUND: The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China). METHODS: A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated. RESULTS: A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98). CONCLUSIONS Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.

OBJECTIVE: To utilized the baseline data of the Beijing Fangshan Family Cohort Study, and to estimate whether the association between a healthy lifestyle and arterial stiffness might be modified by genetic effects. METHODS: Probands and their relatives from 9 rural areas in Fangshan district, Beijing were included in this study. We developed a healthy lifestyle score based on five lifestyle behaviors: smoking, alcohol consumption, body mass index (BMI), dietary pattern, and physical activity. The measurements of arterial stiffness were brachial-ankle pulse wave velocity (baPWV) and ankle-brachial index (ABI). A variance component model was used to determine the heritability of arterial stiffness. Genotype-environment interaction effects were performed by the maximum likelihood methods. Subsequently, 45 candidate single nucleotide polymorphisms (SNPs) located in the glycolipid metabolism pathway were selected, and generalized estimated equations were used to assess the gene-environment interaction effects between particular genetic loci and healthy lifestyles. RESULTS: A total of 6 302 study subjects across 3 225 pedigrees were enrolled in this study, with a mean age of 56.9 years and 45.1% male. Heritability of baPWV and ABI was 0.360 (95%CI: 0.302-0.418) and 0.243 (95%CI: 0.175-0.311), respectively. Significant genotype-healthy diet interaction on baPWV and genotype-BMI interaction on ABI were observed. Following the findings of genotype-environment interaction analysis, we further identified two SNPs located in ADAMTS9-AS2 and CDH13 might modify the association between healthy dietary pattern and arterial stiffness, indicating that adherence to a healthy dietary pattern might attenuate the genetic risk on arterial stiffness. Three SNPs in CDKAL1, ATP8B2 and SLC30A8 were shown to interact with BMI, implying that maintaining BMI within a healthy range might decrease the genetic risk of arterial stiffness. CONCLUSION The current study discovered that genotype-healthy dietary pattern and genotype-BMI interactions might affect the risk of arterial stiffness. Furthermore, we identified five genetic loci that might modify the relationship between healthy dietary pattern and BMI with arterial stiffness. Our findings suggested that a healthy lifestyle may reduce the genetic risk of arterial stiffness. This study has laid the groundwork for future research exploring mechanisms of arterial stiffness.
Humans ; Male ; Middle Aged ; Female ; Ankle Brachial Index ; Cohort Studies ; Gene-Environment Interaction ; Vascular Stiffness/genetics* ; Pedigree ; Pulse Wave Analysis/methods* ; Genotype