OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Background/Aims: Endoscopic radiofrequency ablation (ERFA) is a treatment option for superficial esophageal squamous cell neoplasia (ESCN), with a relatively low risk of stenosis; however, the long-term outcomes remain unclear. We aimed to compare the long-term outcomes of patients with widespread superficial ESCN who underwent endoscopic submucosal dissection (ESD) or ERFA. Methods: We retrospectively analyzed the clinical data of patients with superficial ESCN who underwent ESD or ERFA between January 2015 and December 2021. The primary outcome measure was recurrence-free survival. Results: Ninety-two and 33 patients with superficial ESCN underwent ESD and ERFA, respectively. The en bloc, R0, and curative resection rates for ESD were 100.0%, 90.2%, and 76.1%, respectively. At 12 months, the complete response rate was comparable between the two groups (94.6% vs 90.9%, p=0.748). During a median follow-up of 66 months, recurrence-free survival was significantly longer in the ESD group than in the ERFA group (p=0.004), while no significant differences in overall survival (p=0.845) and disease-specific survival (p=0.494) were observed.Preoperative diagnosis of intramucosal cancer (adjusted hazard ratio, 5.55; vs high-grade intraepithelial neoplasia) was an independent predictor of recurrence. Significantly fewer patients in the ERFA group experienced stenosis compare to ESD group (15.2% vs 38.0%, p=0.016). Conclusions The risk of recurrence was higher for ERFA than ESD for ESCN but overall survival was not affected. The risk of esophageal stenosis was significantly lower for patients who underwent ERFA.

Objective To analyze the trends in disease burden and risk factors of depression among the elderly population in China from 1990 to 2021,and to provide a theoretical basis for the prevention,treatment,and policy-making of geriatric depression in China.Methods Data on the disease burden of geriatric depres-sion in China from 1990 to 2021,including the number of incident cases,disability-adjusted life years(DALYs),incidence rate,and DALY rate,were extracted from the 2021 Global Burden of Disease(GBD)database.The Joinpoint regression model was used to analyze the trends by calculating the annual percentage change(APC)and average annual percentage change(AAPC).The autoregressive integrated moving average(ARIMA)model was employed to predict the disease burden of geriatric depression over the next five years.Population attributable fractions(PAFs)were used to describe the risk factors for geriatric depression in China in 1990 and 2021.Results From 1990 to 2021,the number of incident cases and the incidence rate of geri-atric depression in China showed an overall upward trend.The most significant increase in incidence was ob-served in the 60-64 age group,while the prevalence rate increased notably in the ≥ 95 age group.The DALY rate showed the most pronounced upward trend in the 65-69 age group.The incidence,prevalence,and DALY rates of geriatric depression were higher in women than in men.Major risk factors included child-hood sexual abuse and intimate partner violence,with the impact of intimate partner violence being particular-ly significant among women.The ARIMA model predicted that the incidence,prevalence,and DALY rates of geriatric depression in China would decline over the next five years,with a greater decline observed in women than in men.Conclusions From 1990 to 2021,the incidence,prevalence,and DALY rates of geriatric de-pression in China showed an overall upward trend,with higher rates observed in women than in men.Greater attention should be paid to the elderly female population,with a focus on early prevention to reduce the dis-ease burden of geriatric depression.

Objective:To evaluate the clinical efficacy of the V-shaped bone tunnel technique at the base of the distal phalanx for treating tendinous mallet finger.Methods:A retrospective analysis was conducted on clinical data from patients with tendinous mallet finger treated in the Department of Hand and Foot Surgery at Linyi People’s Hospital between August 2022 and November 2023. Two oblique bone tunnels were created in a V-shaped configuration at the dorsal base of the distal phalanx, adjacent to the extensor tendon insertion, using a 0.8 mm Kirschner wire. A 4-0 double-needle monofilament tendon suture was passed through the tunnels to secure the ruptured extensor tendon to the base of the distal phalanx, followed by fixation of the distal interphalangeal (DIP) joint with a 1.0 mm Kirschner wire. The Kirschner wire was removed at 4 weeks postoperatively to initiate functional exercises. Regular follow-up was conducted to monitor wound healing and functional recovery of the DIP joint. At the final follow-up, the range of flexion and extension of the DIP joint was measured, and treatment outcomes were evaluated using Crawford’s mallet finger evaluation criteria, which classified results into four grades: excellent, good, fair, and poor.Results:Fifteen patients (16 fingers) were included, comprising 11 males and 4 females, with a mean age of 44.5 years (range: 17-65 years). The injured fingers included 2 index, 4 middle, 5 ring, and 5 little fingers, all presenting with DIP joint flexion deformity and limited active extension. Postoperative follow-up ranged from 6 to 28 months (mean: 17 months). All wounds healed primarily without complications such as infection or skin necrosis, and no cases of tendon re-rupture occurred. At the final follow-up, the measurement results of flexion and extension range of motion of the affected fingers at the DIP joint were as follows: the maximum flexion angle of all 16 fingers was 45°, among which 7 fingers had an extension angle of 0°, 8 fingers had limited extension ranging from 1° to 10°, and 1 finger had limited extension of 15°. Among the 16 fingers, 7 fingers were rated as excellent, 8 fingers as good and 1 finger as fair.Conclusion:The V-shaped bone tunnel technique for tendon-to-bone reattachment of the extensor tendon insertion is a simple and effective method for treating tendinous mallet finger. It provides satisfactory functional recovery, improves finger appearance, and is associated with minimal complications.

Objective To evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective:To compare the pregnancy outcomes of surviving fetuses in monochorionic diam-niotic(MCDA)twin pregnancies after selective feticide or spontaneous single intrauterine fetal demise(sIUFD),and to explore the influencing factors of prognosis.Methods:A total of 219 cases of intra-uterine death of one fetus in MCDA twin pregnancies admitted to Peking University Third Hospital from September 2010 to August 2021 were collected.According to the mode of fetal death,they were divided into the spontaneous sIUFD group(120 cases)and the selective feticide group(99 cases).Data on the maternal conditions during pregnancy,the situation of the intrauterine-dead fetus,and pregnancy out-comes were collected for retrospective case-analysis.Results:The live-birth rates of surviving fetuses in the spontaneous sIUFD group and the selective feticide group were 85.0％and 81.8％respectively,and the total perinatal survival rates of surviving fetuses were 73.3％and 81.8％respectively,and there were no statistically significant differences.Compared with the spontaneous sIUFD group,the selective feticide group had a greater gestational week at delivery,and lower rate of preterm birth before 37 weeks,neonatal asphyxia,and early neonatal mortality.Using the gestational week at delivery as the outcome variable,Cox regression analysis showed that the mode of fetal death was not a risk factor affecting the gestational week at delivery of the surviving fetus,while gestational hypertension and the gestational week of fetal death were independent risk factors affecting the gestational week at delivery of the surviving fetus.Using preterm birth before 37 weeks,intrauterine death of the surviving fetus,and abnormal neonatal cranial ultrasound as outcome variables respectively,unconditional logistic regression analysis showed that the mode of fetal death,the gestational week of fetal death,the position of the dead fetus,and fetal complications were independent risk factors affecting the outcomes of the above-mentioned survi-ving fetuses.According to the results of the univariate analysis,the above risk factors were included in the multivariate regression analysis,and the results were the same as those of the univariate analysis.Conclusion:For MCDA twin pregnancy patients with severe twin-related complications,the prognosis of surviving fetuses after selective feticide is better.The proactive intrauterine intervention and treatment are of great significance for improving the prognosis of surviving fetuses.

Objective To study the three-dimensional changes of soft and hard tissue in male patients with unilateral non-syndromic cleft lip and palate in the mixed dentition period before and after maxillary protraction.Methods Twenty male patients with unilateral non-syndromic cleft lip and palate in the mixed dentition period treated by maxillary anterior traction in the Department of Orthodontics of Affiliated Stomatological Hospital of Nanjing Medical University were selected(average age(10.6±1.23)years old).Cone beam CT was taken before and after treatment.Dolphin 3D 11.95 software was used for three-dimensional measurement and analysis.SPSS 25.0 software package was used for statistical analysis.The self-controlled paired t test was used to compare the changes in soft and hard tis-sues of male patients with unilateral cleft lip and palate before and after treatment.The changes in the anterior displacement of the ANS point,the anterior displacement of point A,and the posterior displacement of point B were tested using the one-sample t test.Results The sagittal skeletal changes were significantly increased in ∠ SNA(P＜0.01),∠ANB(P＜0.01),Y axis(P＜0.05),the forward displacement of ANS point(P＜0.01)and A point(P＜0.01)and the backward displacement of B point(P＜0.01),but ∠SNB(P＜0.05)was decreased significantly.The vertical skeletal changes showed that ∠MP-FH(P＜0.01),∠MP-SN(P＜0.05)and the dis-tance of ANS-Me(P＜0.05)were increased significantly,but ∠SN-PP(P＜0.01)was decreased significantly.The dental changes inclu-ding ∠U1-NA(P＜0.01),the distance of U1-NA(P＜0.01),∠U1-SN(P＜0.01),overjet and the Wits were increased significantly,but ∠ L1-NB(P＜0.01),the distance of L1-NB(P＜0.01)and ∠L1-MP(P＜0.01)were decreased significantly.The changes of soft tis-sue including ∠ S-Ns-Sn(P＜0.01),∠ Sn-Ns-Bs(P＜0.01),the distance of UL-EP(P＜0.01)and LL-UL(P＜0.01)were increased sig-nificantly.Conclusion After the treatment of maxillary protraction,the forward growth of maxilla will be possibly promoted on patients with cleft lip and palate in the peak of growth timing,as well as the intermaxillary relationship and soft tissue profile,but the side effects should be paid attention to.

Objective:To analyze the effect of emodin on apoptosis and oxidative damage of PC12 cells induced by hypoxia/re-oxygenation and its corresponding mechanism.Methods:PC12 cells were cultured in vitro and their neural differentiation was induced.Cells were divided into control group,model group,low concentration emodin group(30 mmol/L),high concentration emodin group(90 mmol/L)and high concentration emodin+GW441756(90 mmol/L+6.3 μmol/L)group,excepted for control group,other groups were treated with hypoxia and reoxygenation,and viability of PC12 cells was determined by CCK-8 method;levels of LDH release,SOD,MDA,IL-1β and TNF-α were measured by kits;PC12 cell apoptosis was detected by flow cytometry,expressions of nerve growth factor(NGF)/tropomyosin receptor kinase A(TrkA)pathway proteins in PC12 cells were determined by Western blot.Results:Compared with control group,PC12 cell activity,SOD level,NGF,and p-TrkA/TrkA in model group were decreased(P<0.05),while LDH release,apoptosis rate,MDA,IL-1β and TNF-α levels were increased(P<0.05);compared with model group,PC12 cell activity,SOD level,NGF,and p-TrkA/TrkA in low concentration emodin group and high concentration emodin group were increased(P<0.05),while LDH release,apoptosis rate,MDA,IL-1β and TNF-α levels were decreased(P<0.05);compared with high concen-tration emodin group,PC12 cell activity,SOD level,NGF,and p-TrkA/TrkA in high concentration emodin+GW441756 group were decreased(P<0.05),while LDH release,apoptosis rate,MDA,IL-1β and TNF-α levels were increased(P<0.05).Conclusion:Emodin can inhibit oxidative stress and inflammatory damage of PC12 cells induced by hypoxia/reoxygenation,and inhibit apoptosis by activating NGF/TrkA pathway.

Objective To explore the differences in therapeutic efficacy and possible mechanism of different routes of administration of fullerene nanoparticles in the treatment of radiation retinopathy.Methods Eight-week-old adult male SD rats were randomly divided into blank group(Control),irradiation group(X-Ray),irradiation+vitreous cavity administration group[X+F(IVT)],irradiation+ocular surface administration group[X+F(OS)],and irradiation+intravenous administration group[X+F(IV)],with 5 rats in each group.The blank group was not treated,the irradiation groups exposed to X-ray irradiation to establish the model,and fullerenol nanoparticles were given to the treatment groups through different routes after irradiation.At 7,14,and 28 d after modeling,body weight and fundus changes were measured to evaluate drug safety,retinal optical coherence tomography(OCT)was used to observe the change in retinal tissue structure,and electroretinography(ERG)was applied for oscillatory potentials(OPs)to evaluate visual function.CD31 immunofluorescence staining was carried out to evaluate retinal endothelial vascular status,and in vivo imaging was utilized to evaluate the accumulation of fullerenol nanoparticles in the eyes.Results The growth curves of body weight demonstrated that fullerenol nanoparticles did not affect the growth and development of rats,with no statistical difference between the treatment groups and the control group.Irradiation resulted in a significant reduction in visual function,decreased amplitudes of a-wave and b-wave,and declined OPs(P<0.01),and significantly increased thicknesses of the ganglion cell layer(GCL)and the inner nuclear layer(INL)in the retinas,as evidenced by OCT(P<0.01),along with a notably absent presence of CD31-positive cells(P<0.01).Notably,the X+F(IVT)group obtained significantly improved visual function after intravitreal administration,effectively maintained thickness of the GCL and INL,and prevention against the loss of CD31-positive cells(P<0.01).However,no such effective results were observed in the irradiated groups receiving intravenous either ocular surface administration.In vivo imaging revealed that intravitreal administration maintained high ocular accumulation of fullerene for 96 h,while ocular surface administration sustained these concentrations for only 12 h.Intravenous administration,in contrast,only led to a predominant drug distribution in vascular-rich areas,but reduced ocular accumulation.Conclusion Fullerene nanoparticles possess a therapeutic effect on radiation retinopathy,and the intravitreal administration route demonstrates better efficacy than ocular surface and intravenous administration.

AIM To establish the preparation process and quality standard for Zhenggu Pills.METHODS With decoction time,decoction frequency and water addition as influencing factors,comprehensive score for extract yield and transfer rates of epicatechin and naringin as an evaluation index,the decoction process was optimized by orthogonal test.With sugarless paste relative density,medicinal powder fineness,sugarless paste-corn starch ratio,drying temperature and drying time as influencing factors,soft material traits,pill formability,moisture and disintegration time limit as evaluation indices,the formability process was optimized by single factor test.TLC was adopted in the qualitative identification of Dipsaci Radix,salt-processed Psoraleae Fructus,cooked Rhei Radix et Rhizoma and Notoginseng Radix et Rhizoma.HPLC was used for the content determination of paeoniflorin and naringin.RESULTS The optimal decoction process was determined to be 0.5 h for decoction time,two times for decoction frequency,and 10 times for water addition,the comprehensive score was 0.93.The optimal formability process was determined to be 1.21-1.22 for sugarless paste relative density,80 mesh for medicinal powder fineness,1∶0.17-1∶0.18 for sugarless paste-corn starch ratio,70 ℃ for drying temperature,and 24 h for drying time,good soft material traits and pill formability were observable,and moisture and disintegration time limit accored with 2020 edition of Chinese Pharmacopoeia requirements.The TLC spots were clear without negative interference.Two constituents showed good linear relationships within 61.30-490.41 μg/mL(r=0.999 8)and 3.27-26.18 μg/mL(r=0.999 8),whose average recoveries were 100.15％and 98.15％with the RSDs of 0.55％and 2.30％,respectively.CONCLUSION This stable,reliable and specific method can be used for the production and quality evaluation of Zhenggu Pills.