Evidence indicates that metabolic reprogramming characterized by the changes in cellular metabolic patterns contributes to the pathogenesis of pulmonary fibrosis(PF).It is considered as a promising ther-apeutic target anti-PF.The well-documented against PF properties of Tanshinone ⅡA(Tan ⅡA)have been primarily attributed to its antioxidant and anti-inflammatory potency.Emerging evidence suggests that TanⅡA may target energy metabolism pathways,including glycolysis and tricarboxylic acid(TCA)cycle.However,the detailed and advanced mechanisms underlying the anti-PF activities remain obscure.In this study,we applied[U-13C]-glucose metabolic flux analysis(MFA)to examine metabolism flux disruption and modulation nodes of Tan ⅡA in PF.We identified that Tan ⅡA inhibited the glycolysis and TCA flux,thereby suppressing the production of transforming growth factor-β1(TGF-β1)-dependent extracellular matrix and the differentiation and proliferation of myofibroblasts in vitro.We further revealed that Tan ⅡA inhibited the expression of key metabolic enzyme hexokinase 2(HK2)by inhibiting phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxia-inducible factor 1α(HIF-1α)pathway activities,which decreased the accumulation of abnormal metabolites.Notably,we demonstrated that Tan ⅡA inhibited ATP citrate lyase(ACLY)activity,which reduced the collagen synthesis pathway caused by cytosol citrate consumption.Further,these results were validated in a mouse model of bleomycin-induced PF.This study was novel in exploring the mechanism of the occurrence and develop-ment of Tan ⅡA in treating PF using 13C-MFA technology.It provided a novel understanding of the mechanism of Tan ⅡA against PF from the perspective of metabolic reprogramming.

Objective The development of the expert consensus on self-management of skin adverse reactions in patients undergoing targeted cancer therapy(hereinafter referred to as"the consensus")aims to enhance the effectiveness of self-management for skin-related adverse reactions in cancer patients receiving targeted therapy.It seeks to reduce the incidence of these reactions and alleviate their severity.Methods Utilizing evidence-based approaches,a systematic search was conducted across both domestic and international databases and relevant websites.This process included the evaluation and summarization of pertinent evidence to create a preliminary draft of the consensus.Through 2 rounds of Delphi expert inquiries and a round of expert panel discussion,the content was refined,leading to the final draft of the consensus.Results The consensus comprises 11 sections:gathering information before medication,identifying risk factors prior to medication,self-assessment and proactive reporting,skin cleansing,skin moisturizing,sun protection,makeup application,appropriate clothing,engaging in household activities,prophylactic medication,and common management techniques.Conclusion This consensus provides a valuable reference for clinical nurses to guide cancer patients in the self-management of skin adverse reactions associated with targeted drug therapy.

Objective: To investigate the function of FAK / Twist1 signaling pathway during craniosynostosis closure. Methods: Ten days old rats were divided into a control group (n = 50) and a rotation group (n = 50) . Both of them were made a approximately 0. 5 cm circle bone window at the midpoint of the lambdoid suture of the rat.The bone flaps were left free without damaging the dura mater. The bone flaps in the control group were repositioned in situ , and the bone flaps in the rotation group were rotated 180 ° and repositioned 3 weeks later. Then the experiments were performance as followed :open field test , measurement of body weight , head circumference , bone flap area , and thickness of bone flap in the two groups , observation of cranial suture closure by microscopy and HE staining , FAK / Twist1 expression determined by Western blot , real⁃time PCR , and immunohistochemical staining in the bone flap and dure , respectively. Results: The cranial sutures was completely closed in the rotation groupand that was open in the control group through detecting by microscopic examination and HE staining. The thickness of the bone flap in the derotation group was greater than that in the control group , with statistical significance (P < 0. 01) . There were no significant differences between two groups in head circumference , weight , bone flap area , and operative area. The results of behavioral test showed that after the closure of cranial suture , the acsion of FAK was significantly increased in the calvaria and dura as well as Twsit1 was significantly decreased in the dura in rotating group measuring by Western blot , real⁃time PCR , and immunohistochemical staining (P < 0. 05) . Conclusion FAK/Twist1 may play an important role in craniosynostosis after rotation.

Objective: To explore the growth characteristics of rat calvaria by detecting the calvaria of SD rats in different periods. Methods: The calvaria of SD rats at 1 , 4 , 7 , 10 , and 12 weeks from the same littermate were selected (3 rats per week) . Real⁃time PCR and Western blot techniques were used to detect the expression of focal adhesion kinase ( FAK) Ⅳ phosphatidylinositol 3 kinase/protein kinase B ( PI3K/AKT ) signal pathway in the calvaria , and the role of FAK⁃PI3K/AKT in the growth and development of the calvaria was analyzed by correlation. Results: The increase of brain volume and the thickness of calvaria increased synchronously , the expression of FAK was positively correlated with the changes of meridians , and the expression of FAK was positively correlated with the expression of PI3K/AKT. Conclusion The expression of FAK is related to the growth and development of rat skull. FAK plays a role in calvaria by activating PI3K/AKT signal pathway. FAK may be used as a marker of rapid skull growth and development , which provides a basic theoretical basis for the timing of clinical skull defect repair and treatment.

Objective:To evaluate the efficacy of continuous infusion of lidocaine via urinary catheter for postoperative analgesia in patients undergoing urological surgery.Methods:Forty male American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients, aged 65-75 yr, with body mass index of 18-25 kg/m 2, scheduled for elective percutaneous nephrolithotomy, were divided into 2 groups ( n=20 each) using a random number table method: continuous infusion of lidocaine through urinary catheter group (group L) and patient controlled intravenous analgesia (PCIA) group (group PCIA). All the patients underwent total intravenous anesthesia, and a matched type of sterile urethral irrigation catheter was inserted after the operation.In group L, 0.5% lidocaine was continuously infused at a rate of 5 ml/h via the urinary catheter, while the equal volume of 0.9% normal saline was continuously infused via the urinary catheter, and PCIA was connected in group PCIA.PCIA solution contained sufentanil 125 μg (diluted to 250 ml in normal saline), and the PCA pump was set up with a 5 ml bolus dose, a 15 min lockout interval and background infusion at a rate of 5 ml/h.When visual analogue score was>4, sufentanil 0.05 μg/kg was injected intravenously as rescue analgesic.The development and severity of catheter-related bladder discomfort (CRBD) were recorded immediately at the end of the operation (T 1), and at 6 h (T 2), 24 h (T 3) and 48 h (T 4) after the operation, respectively.Riker sedation-agitation scale (SAS) score was recorded at T 1, 2, and QoR-9 scale was recorded at T 3, 4.The concentrations of serum cortisol (Cor), norepinephrine (NE), epinephrine (E) and blood glucose (Glu) were measured by enzyme linked immunosorbent assay.First off-bed time, exhaust time, length of hospital stay after surgery, and the requirement for rescue analgesia and adverse reactions (nausea and vomiting, respiratory depression, hypotension, skin itching) within 48 h after the operation were recorded. Results:Compared with group PCIA, the incidence of CRBD and the severity were significantly decreased at T 1-4, SAS score was decreased at T 1, 2, QoR-9 score was increased at T 3, 4, Cor, NE, E and Glu concentrations were decreased at T 1-4, the incidence of postoperative rescue analgesia was decreased, first off-bed time, exhaust time and length of hospital stay after surgery was shortened, and the incidence of postoperative nausea and vomiting, respiratory depression, hypotension, skin itching was decreased in group L ( P<0.05). Conclusion:Continuous infusion of lidocaine through the urinary catheter can provide good postoperative analgesia, reduce postoperative stress response and adverse reactions, and facilitate early postoperative recovery in patients undergoing urological surgery.

Objective:To understand the current status of foreign dual-degree programs of Medical Doctor (MD) and Master of Public Health (MPH) and provide evidence-based decision-making reference for promoting the education of high-level applied public health talents in China.Methods:The list of involved institutions and information of foreign MD-MPH dual-degree programs was collected through literature retrieval, online information searching, and additional survey of key figures. We extracted the details of each project regarding professional fields, core competence, length of schooling, teaching and learning arrangement, internship eligibility, and graduation assessment. Python 3.8.0 was used for data cleaning, and the occurrence frequency of related items in each dimension was calculated.Results:A total of 99 MD-MPH programs from 104 foreign institutions were included, among which 97.1% of them were implemented in universities from the United States. The School of Public Health provided 42.4% (42/99) of the programs. Epidemiology was the major discipline set up among most programs, accounting for 12.0% (29/241) of all the specialties involved. Epidemiological research methods, health policy management and practice, and public health practice were the top 3 core competencies to be mastered. Of the 99 programs, 87 gave information on the length of the program, of which 74.7% (65/87) were five years, 6.9% (6/87) were four years, and 18.4% (16/87) included both 4-year and 5-year programs.Conclusions:The international MD-MPH programs were sophisticated and mainly organized by the School of Public Health alone or in conjunction with the School of Medicine. Epidemiology is the core course and competence objective, with a length of 4-5 years. Through learning experience from international MD-MPH programs and the Chinese unique medical development background, China should optimize its medical education system to develop a suitable talent training strategy for MD-MPH dual-degree programs in the new era.

Objective:To preliminarily study the effect of Q self-traction endoscopic submucosal dissection (Q-ESD) on treatment of large early esophageal cancer (EEC).Methods:A retrospective analysis was performed on the data of 82 cases of large EEC (single lesion>1/2 cross-section diameter or longitudinal diameter length >5 cm) who underwent ESD on Fujian Provincial Hospital between January 2015 and December 2018. According to the treatment schedule, patients were divided into the conventional ESD group (n=44) and the Q-ESD group (n=38). The procedural area, time, and speed, en bloc resection rate, complete resection rate and complications of the two groups were analyzed.Results:All of the 82 lesions were resected completely under endoscope. There was no statistical difference in the procedural area [779.8 (329.9-2 552.5)mm 2 VS 875.7 (417.8-1 914.8)mm 2, U=155, P=0.636], procedural time [63 (41-177)min VS 59 (42-169)min, U=171, P=0.167] and complete resection rate [94.7% (36/38) VS 93.2% (41/44), χ2=0.086, P=0.769] between the Q-ESD group and the conventional ESD group. Compared with the conventional ESD group, the Q-ESD group had a faster dissection speed [14.9 (5.4-20.8) mm 2/min VS 9.0 (5.0-19.5) mm 2/min, U=142, P=0.035], lower muscularis propria injury rate [7.9% (3/38) VS 27.3% (12/44), χ2=5.123, P=0.023], and a lower stricture rate [5.3% (2/38) VS 20.5% (9/44), χ2=4.051, P=0.044]. No other adverse events occurred except for one case of perforation in the conventional ESD group. Conclusion:The new traction technique of Q-ESD is a safe and effective treatment for large EEC.

Objective:To evaluate the efficacy and safety of budesonide viscous suspension (BVS) in preventing extensive esophageal stenosis after endoscopic submucosal dissection(ESD).Methods:Data of 62 cases of early esophageal neoplasms or precancerous lesions receiving ESD whose postoperative mucosal defects were more than half the circumference of the esophageal lumen at Fujian Provincial Hospital from October 2014 to December 2018 were retrospectively studied. The patients were divided into the BVS group who received BVS therapy (n=24) and the control group who received no intervention (n=38). The incidence of postoperative stenosis, the number of bougie dilation procedures and complications were compared between the two groups. Risk factors for postoperative stricture were analyzed by logistic regression.Results:The incidence of postoperative stenosis [16.7% (4/24) VS 47.3% (18/38), P=0.005], the number of bougie dilation procedures (1.50±0.58 VS 2.70±1.09, P=0.039) in the BVS group were significantly lower than those in the control group. No serious adverse events such as perforation or massive hemorrhage related to BVS were observed in the BVS group. Multivariate logistic regression analysis showed circumferential extension ≥3/4 ( OR=37.970, 95% CI: 6.338-227.482) and non-intervention with BVS( OR=20.962, 95% CI: 3.374-130.243) were the independent risk factors for esophageal stricture after ESD. Conclusion:Administration of BVS is an effective and safe method to reduce the incidence of stenosis and the number of bougie dilation procedures for extensive esophageal stenosis after ESD.

Objective:To evaluate the accuracy of white light conventional endoscopy (CE), endoscopic ultrasonography (EUS) and narrow-band imaging with magnifying endoscopy (ME-NBI) in evaluating the invasion depth of early gastric cardiac cancer, and to explore the diagnostic strategy of preoperative evaluation of invasive depth of early gastric cardiac cancer.Methods:From January 2016 to June 2019, the endoscopic images of 135 patients with early gastric cardiac cancer confirmed by pathology in Fujian Provincial Hospital were retrospectively analyzed. Intramucosal carcinoma (M) and superficial submucosal invasive carcinoma (SM1) were classified as M-SM1 cancer and compared with deep submucosal invasive cancer. The pathological diagnosis after operation was used as gold standard. The accuracy of CE, EUS, ME-NBI and the combination of them in determining the invasion depth of early gastric cardiac cancer was evaluated. Kappa test was performed for consistency test. Kappa value < 0.2 was considered as poor consistency, 0.2 to 0.4 as general consistency, more than 0.4 to 0.6 as medium consistency, more than 0.6 to 0.8 as high consistency, and 0.8 to 1.0 as close to full consistency. Results:The data of 73 patients with early gastric cardiac cancer were enrolled in this study. According to the pathological results after operation, 47 cases were M-SM1 cancer and 26 cases were deep submucosal invasive cancer. The diagnostic accuracy of CE, EUS, ME-NBI and the combination of them before operation were 79.5% (58/73), 72.6% (53/73), 65.7% (48/73) and 87.7% (64/73), respectively. The results of consistency test indicated that the consistency of CE diagnosis and pathological results after operation was medium ( Kappa=0.540, P<0.01), that of EUS and pathological results after operation was general ( Kappa=0.346, P=0.002), that of ME-NBI and pathological results after operation was poor ( Kappa=0.175, P=0.108), while that of the combination of them and pathological results after operation was high ( Kappa=0.724, P<0.01). Conclusions:Compared with single examination method, the combination of CE, EUS and ME-NBI is more accurate in evaluating the invasive depth of early gastric cardiac cancer.

Objective:To establish autoverification rules for coagulation tests in multicenter cooperative units, in order to reduce workload for manual review of suspected results and shorten turnaround time (TAT) of test reports, while ensure the accuracy of results.Methods:A total of 14 394 blood samples were collected from fourteen hospitals during December 2019 to March 2020. These samples included: Rules Establishment Group 11 230 cases, including 1 182 cases for Delta check rules; Rules Validation Group 3 164 cases, including 487cases for Delta check; Clinical Application Trial Group 77 269 cases. Samples were analyzed for coagulation tests using Sysmex CS series automatic coagulation analyzers, and the clinical information, instrument parameters, test results, clinical diagnosis, medication history of anticoagulant and other relative results such as HCT, TG, TBIL, DBIL were summarized; on the basis of historical data, the 2.5 and 97.5 percentile of all data arranged from low to high were initially accumulated; on the basis of clinical suggestions, critical values and specific drug use as well as relative guidelines, autoverification rules and limits were established.The rules were then input into middleware, in which Stage I/Stage II validation was done. Positive coincidence, negative coincidence, false negative, false positive, autoverification pass rate, passing accuracy (coincidence of autoverification and manual verification) were calculated. Autoverification rules underwent trial application in coagulation results reports.Results:(1) The autoverification algorisms involve 33 rules regarding PT/INR, APTT, FBG, D-dimer, FDP,Delta check, reaction curve and sample abnormalities; (2)Autoverification Establishment Group showed autoverification pass rate was 68.42% (7 684/11 230), the false negative rate was 0%(0/11230), coincidence of autoverification and manual verification was 98.51%(11 063/11 230), in which positive coincidence and negative coincidence were respectively 30.09% (3 379/11 230) and 68.42%(7 684/11 230); Autoverification Validation Group showed autoverification pass rate was 60.37%(1 910/3 164), the false negative rate was 0%(0/11 230), coincidence of autoverification and manual verification was 97.79%(3 094/3 164), in which positive coincidence and negative coincidence were respectively 37.42%(1 184/3 164) and 60.37%(1 910/3 164); (3) Trialed implementation of these autoverification rules on 77 269 coagulation samples showed that the average TAT shortened by 8.5 min-83.1 min.Conclusions:This study established 33 autoverification rules in coagulation tests. Validation showedthese rules could ensure test quality while shortening TAT and lighten manual workload.