Most patients with pancreatic cancer are already in the locally advanced or metastatic stage at initial diagnosis. While systemic chemotherapy provides clinical benefits for those with mid-to-late-stage pancreatic cancer, its efficacy is often limited by patient tolerance. In response to the dual clinical demands of robust antitumor activity and high targeting specificity, antibody-drug conjugate (ADC) has emerged as a promising solution. By conjugating highly selective monoclonal antibodies with potent cytotoxic small-molecule drugs, ADC achieves precise tumor-targeting while minimizing damage to healthy tissues, which thereby improves treatment tolerance. However, due to the complex pathological features of pancreatic cancer, no ADC has yet been approved for clinical use for this disease. A comprehensive evaluation of factors including ADC-specific targets, payload selection, antibody-drug linkage strategies, drug delivery mechanisms, tissue distribution variability, and tumor heterogeneity will be crucial to advancing the clinical translation of ADC for pancreatic cancer treatment.

Background::Coronavirus disease 2019 (COVID-19) has potential risks for both clinically worsening pulmonary hypertension (PH) and increasing mortality. However, the data regarding the protective role of vaccination in this population are still lacking. This study aimed to assess the safety of approved vaccination for patients with PH.Methods::In this national prospective cohort study, patients diagnosed with PH (World Health Organization [WHO] groups 1 and 4) were enrolled from October 2021 to April 2022. The primary outcome was the composite of PH-related major adverse events. We used an inverse probability weighting (IPW) approach to control for possible confounding factors in the baseline characteristics of patients.Results::In total, 706 patients with PH participated in this study (mean age, 40.3 years; mean duration after diagnosis of PH, 8.2 years). All patients received standardized treatment for PH in accordance with guidelines for the diagnosis and treatment of PH in China. Among them, 278 patients did not receive vaccination, whereas 428 patients completed the vaccination series. None of the participants were infected with COVID-19 during our study period. Overall, 398 patients received inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine, whereas 30 received recombinant protein subunit vaccine. After adjusting for baseline covariates using the IPW approach, the odds of any adverse events due to PH in the vaccinated group did not statistically significantly increase (27/428 [6.3%] vs. 24/278 [8.6%], odds ratio = 0.72, P = 0.302). Approximately half of the vaccinated patients reported at least one post-vaccination side effects, most of which were mild, including pain at the injection site (159/428, 37.1%), fever (11/428, 2.6%), and fatigue (26/428, 6.1%). Conclusions::COVID-19 vaccination did not significantly augment the PH-related major adverse events for patients with WHO groups 1 and 4 PH, although there were some tolerable side effects. A large-scale randomized controlled trial is warranted to confirm this finding. The final approval of the COVID-19 vaccination for patients with PH as a public health strategy is promising.

Background::Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically ill patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI.Methods::TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome was preformed through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. Results::TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1β, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. Conclusion::TSPO may be the key regulator of cellular pyroptosis, and it plays a vital protective role in ARDS occurrence and development.

Objective To explore the differences in scapular motion and shoulder function between patients suffering from rotator cuff tears(RCT)with and without type Ⅲ scapular dyskinesis(SD).Meth-ods Between September 2021 and March 2023,sixteen patients suffering from rotator cuff tears with SD(SD group)and 17 counterparts without SD(non-SD group)were recruited from the Sports Hospital of the General Administration of Sport of China.Their scapular motion was assessed by measuring three parameters in the X-rays,including scapular spine line(LSS),scapular upward rotation angle(SU-RA),and coracoid upward shift distance(CUSD).Moreover,their shoulder range of motion in flexion,abduction and external rotation were recorded,and further evaluated using the Pain Visual Analog Scale(VAS)and American Shoulder and Elbow Surgeons Score(ASES).Results No significant differenc-es were found between the two groups in the average score of SURA,CUSD and LSS at 0°～30° shoul-der abduction,or in that of CUSD and LSS at 60°～90°shoulder abduction.However,the average SU-RA score of the SD group at 60°～90°shoulder abduction was significantly greater than the other group(P<0.05).The shoulder ranges of motion during active flexion,abduction and external rotation were significantly smaller in the SD group than in the non-SD group(P<0.05).Moreover,the average VAS score in the SD group was significantly higher than the non-SD group(P<0.05),while the average ASES score was significantly lower than the latter group(P<0.05).Conclusions RCT patients type III SD exhibits greater scapular upward rotation during shoulder abduction compared to those without SD.Moreover,the former patients suffer from more severe pain and have worse shoulder range of motion and functional performance than the latter.

Objective:To evaluate the effectiveness of correcting breast ptosis using the rotational filling of an inferolaterally pedicled tongue-shaped parenchymal flap via a double periareolar incision.Methods:A retrospective study was conducted on 34 female patients (68 breasts) with breast ptosis treated at the Department of Plastic Surgery at the Affiliated Friendship Plastic Surgery Hospital of Nanjing Medical University from January 2016 to June 2023. The patients＇ ages ranged from 23 to 53 years, with an average of (37.4±7.9) years. All patients underwent correction of breast ptosis using an inferolaterally pedicled tongue-shaped parenchymal flap via a double periareolar incision. Pre-operative and post-operative measurements were taken to assess the corrective outcomes, including mammary base width (MBW), areola diameter (AD), nipple-to-nipple distance (NN), suprasternal notch-to-nipple distance (SSN-N), nipple-to-inframammary fold distance (N-IMF), and thoracic circumference at the nipple level (TN). Patients＇ satisfaction was assessed using the BREAST-questionnaire (BREAST-Q) module.Results:Postoperative first-stage wound healing was achieved in all 34 patients without complications such as hematoma, infection, or nipple necrosis. The follow-up period ranged from 6 to 60 months, with a median of 12 months. Early postoperative observations showed periareolar folds, which disappeared within 3 to 6 months in 31 cases, while mild periareolar folds, persisted for up to 12 months in 3 cases. Four patients reported reduced nipple sensation postoperatively. Measurements showed a statistically significant increase in TN and a reduction in NN, SSN-N, AD, N-IMF, and MBW compared to preoperative values (all P<0.001). BREAST-Q scores indicated significant improvements in satisfaction with breasts, psychosocial well-being and physical well-being, with preoperative scores of (21.6±8.9), (42.4±11.9) and (49.7±12.9) scores increasing to (82.3±8.5), (81.9±8.1) and (81.2±8.3) scores, respectively (all P<0.001). Conclusions:The double periareolar incision technique with rotational filling of an inferolaterally pedicled tongue-shaped glandular flap is a safe and effective method for correcting breast ptosis.

Objective To explore the effect of semaglutide on myocardial injury markers and cardiovascular and cerebrovascular events in patients with type 2 diabetes mellitus(T2DM).Methods A total of 100 patients with T2DM admitted to Xingtai Third Hospital from January to December 2021 were selected as the research subjects,and they were divided into the control group and the observation group by using the random number table,with 50 patients in each group.The patients in both groups were given lifestyle interventions,including reasonable diet,moderate exercise,smoking cessation and alcohol restriction.On this basis,the patients in the control group were given the conventional hypoglycemic drug metformin,and the patients in the observation group were given metformin and semaglutide injection.The patients in both groups were treated for 12 months.Before and after treatment,fasting venous blood was collected from the patients in the two groups,and the levels of glycated hemoglobin(HbA1c)were measured by high-performance liquid chromatography,the fasting plasma glucose(FPG),2-hour postprandial glucose(2hPG),total cholesterol(TC),triglycerides(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were measured by using the glucose oxidase method,and the levels of serum cardiac troponin Ⅰ(cTnⅠ),myoglobin(Myo),and lactate dehydrogenase(LDH)were measured by using the electro-chemiluminescence or enzyme-linked immunosorbent assay.The systolic blood pressure(SBP)and diastolic blood pressure(DBP)in the right upper arm of patients were measured by using an electronic blood pressure monitor.The cardiovascular and cerebrovascular events such as myocardial infarction,unstable angina,heart failure,cardiogenic shock,arrhythmia,ischemic stroke,and hemorrhagic stroke during treatment of patients in two groups were recorded.Results Before treatment,there was no statistically significant difference in the levels of FPG,2hPG,and HbA1c of patients between the two groups(P＞0.05).After treatment,the levels of FPG,2hPG,and HbA1c of patients in the two groups were significantly lower than those before treatment(P＜0.05);and the levels of FPG,2hPG,and HbA1c of patients in the observation group were significantly lower than those in the control group(P＜0.05).Before treatment,there was no statistically significant difference in SBP and DBP of patients between the two groups(P＞0.05).There was no statistically significant difference in SBP and DBP of patients before and after treatment in the control group(P＞0.05);after treatment,the SBP and DBP of patients in the observation group were significantly lower than those before treatment and in the control group(P＜0.05).Before treatment,there was no statistically significant difference in the levels of TC,TG,LDL-C,and HDL-C of patients between the two groups(P＞0.05).There was no statistically significant difference in the levels of TC,TG,LDL-C,and HDL-C of patients before and after treatment in the control group(P＞0.05);after treatment,the levels of TC,TG,and LDL-C of patients in the observation group were significantly lower than those before treatment,while the level of HDL-C was significantly higher than that before treatment(P＜0.05);after treatment,the levels of TC,TG,and LDL-C of patients in the observation group were significantly lower than those in the control group,while the level of HDL-C was significantly higher than that in the control group(P＜0.05).During the treatment period,the incidence of cardiovascular and cerebrovascular events of patients in the control and observation groups was 18.0％(9/50)and 4.0％(2/50),respectively;the incidence of cardiovascular and cerebrovascular events of patients in the observation group was significantly lower than that in the control group(x2=4.320,P＜0.05).Before treatment,there was no statistically significant difference in levels of cTnⅠ,Myo,and LDH of patients between the two groups(P＞0.05).There was no statistically significant difference in the levels of cTnⅠ,Myo,and LDH of patients before and after treatment in the control group(P＞0.05);after treatment,the levels of cTnⅠ,Myo,and LDH of patients in the observation group were significantly lower than those before treatment and in the control group(P＜0.05).Conclusion Semaglutide can obviously reduce blood glucose and pressure,improve blood lipids,reduce the incidence of cardiovascular and cerebrovascular events,and alleviate the degree of myocardial injury in patients with T2DM.

Objective:To investigate the clinical outcomes of sublingual gland flap in the repair of postoperative jaw defects because of chronic phosphorous osteomyelitis(PNJ)and medication-related osteonecrosis of the jaw(MRONT).Methods:3 patients with PNJ and 2 with MRONJ were treated by sublingual gland flap in the repair of the postoperative jaw defet.The treatment effects were evalua-ted by clinical obseration.Results:In the 5 patients the wound healed well within 2 weeks postoperatively,with no infection and with normal sublingual gland function after surgery.Conclusion:The use of sublingual gland flap is an effective and feasible method for re-pairing local defects in the mandibles after surgery for chronic PNJ and MRONJ.

Objective To study the clinical efficacy and safety of disitamab vedotin(RC48)in the third-line and above third-line treatment of advanced gastric cancer.Methods The clinical data of 30 patients with advanced gastric cancer who had previously failed to receive at least two systemic chemotherapy regimens from August 2020 to August 2022 in Nantong Tumor Hospital were retrospectively analyzed.According to different treatment regimens,they were divided into RC48 group(n=15)and control group(chemotherapy/targeted/immune monotherapy)(n=15).The objective response rate(ORR),disease control rate(DCR),progression-free survival(PFS),overall survival(OS)and treatment-related adverse reactions were observed in the two groups.Results The median follow-up time was 7.5 months.The ORR of RC48 group and control group was 20%vs.0%(P=0.224),DCR was 53.3%vs.20%(P=0.128),mPFS was 4 months vs.3 months(P=0.479),mOS was 18 months vs.5 months(P=0.043).In terms of safety,the most common adverse reactions in the RC48 group and the control group were leukopenia and neutropenia.The overall incidence of adverse reactions in the two groups was compa-rable,and there were no fatal adverse events.Conclusion RC48 has a certain effect in the third-line and above third-line treatment of advanced gastric cancer,and patients are well tolerated.

Purpose/Significance A prediction model is constructed based on real-world data to achieve prediction and early screening of type 2 diabetic microvascular complications.Method/Process Based on the real world data of Nanjing Drum Tower Hospital in the past 10 years,a particle swarm optimization based deep belief network(PSO-DBN)prediction model for microvascular complica-tions in type 2 diabetes mellitus is constructed by taking test results and medical record documents into consideration.Result/Conclusion The PSO-DBN model can predict diabetic microvascular complications,and the performance is better than that of random forest and sup-port vector machine(SVM)benchmark models,it provides references for the research of disease prediction model of real-world data.

AIM:This study investigates the apoptotic and autophagic effects of atractylodin on lung cancer cells,elucidating the underlying molecular mechanisms.METHODS:Non-small cell lung cancer(NSCLC)A549 and H460 cells,in addition to non-cancerous HBE cells,were cultured in vitro.The effects of atractylodin at various concen-trations on cell viability were assessed using CCK-8 assay.Apoptotic effects were evaluated through Hoechst staining and flow cytometry,while Western blot analysis was performed to detect changes in protein expressions associated with apopto-sis and autophagy,including P62,beclin-1,microtubule-associated protein 1 light chain 3(LC3),Kelch-like epichloro-hydrin(ECH)-associated protein-1(Keap-1),nuclear factor E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Autophagic flux was further analyzed using acridine orange(AO)stain-ing,and immunofluorescence for LC3 and Nrf2.Additionally,autophagy inhibition experiments were conducted using chloroquine(CQ),followed by analyses of autophagy and apoptosis.Reactive oxygen species(ROS)levels were quanti-fied using DCFH-DA.RESULTS:Treatment with atractylodin significantly reduced the viability of A549 and H460 lung cancer cells,promoting apoptosis and inducing autophagy.This was evidenced by an increase in acidic autophagic vesi-cles,upregulation of LC3 and beclin-1,and downregulation of P62.Inhibition of autophagy by chloroquine reversed atrac-tylodin-induced apoptosis.Moreover,atractylodin heightened ROS production,inhibited Keap-1,and stimulated the ex-pression of Nrf2,HO-1 and NQO1.CONCLUSION:Atractylodin effectively inhibits the proliferation of lung cancer cells by inducing apoptosis and autophagy.These effects are mediated through the modulation of the ROS/Nrf2/HO-1 sig-naling pathway,underscoring its potential as a therapeutic agent in lung cancer treatment.