Oral squamous cell carcinoma (OSCC) is a common head and neck malignancy. Approximately 50% to 60% of patients with OSCC are diagnosed at a locally advanced stage (clinical staging III-IVa). Even with comprehensive and sequential treatment primarily based on surgery, the 5-year overall survival rate remains below 50%, and patients often suffer from postoperative functional impairments such as difficulties with speaking and swallowing. Programmed death receptor-1 (PD-1) inhibitors are increasingly used in the neoadjuvant treatment of locally advanced OSCC and have shown encouraging efficacy. However, clinical practice still faces key challenges, including the definition of indications, optimization of combination regimens, and standards for efficacy evaluation. Based on the latest research advances worldwide and the clinical experience of the expert group, this expert consensus systematically evaluates the application of PD-1 inhibitors in the neoadjuvant treatment of locally advanced OSCC, covering combination strategies, treatment cycles and surgical timing, efficacy assessment, use of biomarkers, management of special populations and immune related adverse events, principles for immunotherapy rechallenge, and function preservation strategies. After multiple rounds of panel discussion and through anonymous voting using the Delphi method, the following consensus statements have been formulated: 1) Neoadjuvant therapy with PD-1 inhibitors can be used preoperatively in patients with locally advanced OSCC. The preferred regimen is a PD-1 inhibitor combined with platinum based chemotherapy, administered for 2-3 cycles. 2) During the efficacy evaluation of neoadjuvant therapy, radiographic assessment should follow the dual criteria of Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and immune RECIST (iRECIST). After surgery, systematic pathological evaluation of both the primary lesion and regional lymph nodes is required. For combination chemotherapy regimens, PD-L1 expression and combined positive score need not be used as mandatory inclusion or exclusion criteria. 3) For special populations such as the elderly (≥ 70 years), individuals with stable HIV viral load, and carriers of chronic HBV/HCV, PD-1 inhibitors may be used cautiously under the guidance of a multidisciplinary team (MDT), with close monitoring for adverse events. 4) For patients with a poor response to neoadjuvant therapy, continuation of the original treatment regimen is not recommended; the subsequent treatment plan should be adjusted promptly after MDT assessment. Organ transplant recipients and patients with active autoimmune diseases are not recommended to receive neoadjuvant PD-1 inhibitor therapy due to the high risk of immune related activation. Rechallenge is generally not advised for patients who have experienced high risk immune related adverse events such as immune mediated myocarditis, neurotoxicity, or pneumonitis. 5) For patients with a good pathological response, individualized de escalation surgery and function preservation strategies can be explored. This consensus aims to promote the standardized, safe, and precise application of neoadjuvant PD-1 inhibitor strategies in the management of locally advanced OSCC patients.

BACKGROUND:Acute myocardial infarction can cause cardiac remodeling and heart failure,as well as skeletal myopathy,affecting patients'quality of life.Exercise therapy is an important rehabilitation method for patients with heart failure;however,the optimal exercise prescription has not been clarified. OBJECTIVE:To compare the effects of different exercise modes(aerobic exercise,resistance exercise)on skeletal muscle remodeling in rats with acute myocardial infarction induced heart failure and to explore the possible mechanism,so as to provide a basis for optimizing the exercise rehabilitation program. METHODS:Forty-eight Sprague-Dawley rats were randomly divided into sham operation group,myocardial infarction group,aerobic exercise group and resistance exercise group.Coronary artery ligation was used to create model of heart failure.After 3 months,animals in the aerobic exercise group and resistance exercise group underwent 12 weeks of corresponding exercise mode interventions,while those in the sham operation group and myocardial infarction group were kept quietly in mouse cages.After the experiment,maximal running speed and maximal weight-bearing load were measured by graded treadmill exercise test and ladder-climbing test respectively,and heart structure and function were evaluated by echocardiography.The heart was isolated,and hematoxylin-eosin staining and Sirius red staining were performed to detect cardiac remodeling.For the gstrocnemius muscle,ATPase staining was performed to observe changes in muscle fiber type and cell cross-sectional area,dihydroethidium method was used to evaluate reactive oxygen species levels,enzyme-linked immunosorbent method was used to determine malondialdehyde content and antioxidant enzyme activity,western blot was used to determine the expression of ubiquitin-proteasome system proteins,and the number of activated satellite cells(Pax7+/MyoD+)were detected by double immunofluorescence staining. RESULTS AND CONCLUSION:(1)Exercise performance:Compared with the sham operation group,maximal running speed and maximal weight-bearing load in the myocardial infarction group decreased(P<0.05);compared with the myocardial infarction group,the maximal running speed of the aerobic exercise group and the maximal weight-bearing load of the resistance exercise group increased(P<0.05).(2)Cardiac remodeling:Compared with the sham operation group,infarction area,myocardial cell cross-sectional area,and collagen content in the myocardial infarction group increased(P<0.05),while leftventricular ejection fraction and shortening fraction decreased(P<0.05);compared with the myocardial infarction group,there was no statistical difference in the above parameters in both aerobic exercise resistance exercise groups(P>0.05).(3)Skeletal muscle remodeling:Compared with the sham operation group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,superoxide dismutase activity,glutathione peroxidase activity,and the number of activated satellite cells decreased in myocardial infarction group(P<0.05),while reactive oxygen species content,malondialdehyde content,and the protein expression of ubiquitin,MuRF1 and MAFbx increased(P<0.05);compared with the myocardial infarction group,gastrocnemius muscle mass index,superoxide dismutase activity,the number of activated satellite cells increased in both aerobic exercise and resistance exercise groups(P<0.05),while reactive oxygen species content and the protein expression of ubiquitin,MuRF1,and MAFbx decreased(P<0.05);compared with the aerobic exercise group,gastrocnemius muscle mass,gastrocnemius muscle mass index,cell cross-sectional area,reactive oxygen species content,malondialdehyde content,the number of activated satellite cells increased in resistance exercise group(P<0.05),while superoxide dismutase activity,glutathione peroxidase activity down-regulated(P<0.05).To conclude,aerobic exercise and resistance exercise can both improve exercise performance of rats with heart failure,and the mechanism is related to reducing oxidative stress,inhibiting ubiquitin-proteasome system activity and activating satellite cells to improve skeletal muscle remodeling.Aerobic exercise has a better effect on improving skeletal muscle oxidative stress,while resistance exercise has a more significant effect on promoting skeletal muscle regeneration.

Bufalin(BF)has a significant anti-tumor effect, but its clinical application is severely restricted by its high toxicity and poor water solubility. In this study, Scrophularia ningpoensis polysaccharide(SNP)and ursodeoxycholic acid(UDCA) were synthesized into an SNP-UDCA conjugate. BF was encapsulated to prepare BF/SNP-UDCA nanoparticles(NPs). The amphiphilic compound SNP-UDCA was synthesized via the one-step method, and its structure was characterized by Fourier-transform infrared spectroscopy(FT-IR)and proton nuclear magnetic resonance(~1H-NMR). The preparation process of BF/SNP-UDCA NPs was optimized through single-factor investigations. The encapsulation efficiency and drug-loading capacity of BF/SNP-UDCA NPs were determined by high-performance liquid chromatography(HPLC). The molecular form of BF/SNP-UDCA NPs was characterized by using a transmission electron microscope, X-ray diffraction(XRD), and differential scanning calorimeter(DSC). Additionally, the stability of BF/SNP-UDCA NPs was evaluated. The release behavior of BF/SNP-UDCA NPs at different pH values was determined by dialysis. The in vitro anti-tumor effect of BF/SNP-UDCA NPs was evaluated by MTT cytotoxicity assay, flow cytometry for apoptosis, and cellular uptake. The in vitro liver targeting was evaluated by measuring cellular uptake by laser confocal microscopy. The results demonstrated that the SNP-UDCA conjugate was successfully synthesized through an esterification reaction between SNP and UDCA. The preparation process of BF/SNP-UDCA NPs was as follows: the feed ratio of SNP-UDCA to BF was 2∶1, the ultrasonic time was 30 minutes, and the stirring time was two hours. The prepared BF/SNP-UDCA NPs were spherical in shape, with a particle size of(252.74±6.05)nm, an encapsulation efficiency of 65.00%±2.51%, and a drug-loading capacity of 6.80%±0.44%. The XRD and DSC results indicated that BF was encapsulated within the NPs and existed in a molecular or amorphous state. The short-term stability of BF/SNP-UDCA NPs and stability in DMEM medium are good, and their in vitro release behavior followed the first-order equation and was pH-dependent according to the in vitro experiment. Compared with BF, BF/SNP-UDCA NPs at the same concentration showed significantly stronger cytotoxicity and apoptotic effects on HepG2 cells(P<0.05, P<0.01). The uptake of coumarin 6(C6)/SNP-UDCA NPs in HepG2 cells was time-dependent and higher than that in HeLa cells at the same concentration of C6/SNP-UDCA NPs. Moreover, after treatment with SNP, the uptake of C6/SNP-UDCA NPs in HepG2 cells decreased. In conclusion, the preparation process of BF/SNP-UDCA NPs was simple and feasible. BF/SNP-UDCA NPs could enhance the targeting ability and inhibitory effect of BF on liver cancer cells. This study will provide a foundation for liver-targeting nanoformulations of BF.
Bufanolides/pharmacology* ; Nanoparticles/chemistry* ; Humans ; Drug Carriers/chemistry* ; Ursodeoxycholic Acid/chemistry* ; Antineoplastic Agents/pharmacology* ; Polysaccharides/chemistry* ; Scrophularia/chemistry* ; Liver Neoplasms/physiopathology* ; Hep G2 Cells

BACKGROUND: The clinical impact of post-percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) in patients treated with PCI for chronic total occlusion (CTO) was still undetermined. METHODS: All CTO vessels treated with successful anatomical PCI in patients from PANDA III trial were retrospectively measured for post-PCI QFR. The primary outcome was 2-year vessel-oriented composite endpoints (VOCEs, composite of target vessel-related cardiac death, target vessel-related myocardial infarction, and ischemia-driven target vessel revascularization). Receiver operator characteristic curve analysis was conducted to identify optimal cutoff value of post-PCI QFR for predicting the 2-year VOCEs, and all vessels were stratified by this optimal cutoff value. Cox proportional hazards models were employed to calculate the hazard ratio (HR) with 95% CI. RESULTS: Among 428 CTO vessels treated with PCI, 353 vessels (82.5%) were analyzable for post-PCI QFR. 31 VOCEs (8.7%) occurred at 2 years. Mean value of post-PCI QFR was 0.92 ± 0.13. Receiver operator characteristic curve analysis shown the optimal cutoff value of post-PCI QFR for predicting 2-year VOCEs was 0.91. The incidence of 2-year VOCEs in the vessel with post-PCI QFR < 0.91 (n = 91) was significantly higher compared with the vessels with post-PCI QFR ≥ 0.91 (n = 262) (22.0% vs. 4.2%, HR = 4.98, 95% CI: 2.32-10.70). CONCLUSIONS Higher post-PCI QFR values were associated with improved prognosis in the PCI practice for coronary CTO. Achieving functionally optimal PCI results (post-PCI QFR value ≥ 0.91) tends to get better prognosis for patients with CTO lesions.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Tuberous sclerosis complex(TSC)is a rare genetic disease that can lead to benign dysplasia in multiple organs such as the skin, brain, eyes, oral cavity, heart, lungs, kidneys, liver, and bones. Its main symptoms include epilepsy, intellectual disabilities, skin depigmentation, and facial angiofibromas, whilst incidence is approximately 1 in 10 000 to 1 in 6000 newborns. This case presents a middle-aged woman who initially manifested with epilepsy and nodular depigmentation. Later, she developed a lower abdominal mass, elevated creatinine, and severe anemia. Based on clinical features and whole exome sequencing, the primary diagnosis was confirmed as TSC. Laboratory and imaging examinations revealed that the lower abdominal mass originated from the uterus. CT-guided biopsy pathology and surgical pathology suggested a combination of leiomyoma and abscess. With the involvement of multiple organs and various complications beyond the main diagnosis, the diagnostic and therapeutic process for this patient highlights the importance of rigorous clinical thinking and multidisciplinary collaboration in the diagnosis and treatment of rare and challenging diseases.

Objective:To investigate the clinical benefit and application value of the Da Vinci robotic surgical system through bilateral axillary areolar approach in cervical lymph node dissection in obese thyroid carcinoma patients.Methods:The clinical data of 117 patients with thyroid cancer admitted to the thyroid and breast surgery Department of the 960th Hospital of the Chinese PLA Joint Logistic Support Force from January 2018 to June 2023 were retrospectively analyzed. There were 55 males and 62 females, aged from 17 to 64 years, with an average age of (36.05±8.77) years. According to body mass index (BMI), patients were divided into normal group (18.5 kg/m 2≤BMI< 24 kg/m 2, n=60) and obese group (BMI≥28 kg/m 2, n=57). Gender, age, BMI, operation time, postoperative drainage fluid volume, tumor diameter, central lymph node dissection and number of metastasis, cervical lymph node dissection and number of metastasis, postoperative hospital stay, postoperative aesthetic satisfaction score and surgical complications of the two groups were analyzed. SPSS 26.0 statistical software was used to analyze the data. Results:All of patients completed the operation successfully, and neither group was transferred to open surgery. The BMI of obese group was higher than that of normal group [(31.35±3.08) kg/m 2vs (22.53±0.82) kg/m 2, t=20.97, P<0.05]. The maximum tumor diameter in the obese group was greater than that in the normal group [(13.81±10.70) mm vs (10.42±5.53) mm, t=2.17, P<0.05]. There were no significant differences in operation time, number of central lymph node dissection and metastasis, number of cervical lymph node dissection and metastasis and postoperative complications between the two groups ( P>0.05). Conclusions:Utilization of the Da Vinci robotic surgical system via the BABA approach demonstrates both safety and feasibility in obese patients with thyroid carcinoma undergoing lateral cervical lymph node dissection. Importantly, this technique does not increase the risk of surgical complications, thus providing a novel alternative for lateral cervical lymph node dissection in obese thyroid carcinoma patients.

Objective:To explore the suitable prostate cancer screening mode under the medical community for primary hospitals.Methods:From April 2021 to April 2022, a total of 16007 male population ≥50 years from 9 branches of the medical community of the second hospital of Yinzhou participated in this study. They were divided into four groups according to age with group 1 of 50-59 years old, group 2 of 60-69 years old, group 3 of 70-79 years old, and group 4 of 80 years old and above. Serum tPSA was added to the routine physical examination, and the screening positive patients were referred to the referral hospital for further diagnosis and treatment under the mode of medical community. We proposed multi-parametric MRI (mpMRI) for those with serum PSA ≥4 ng/ml and suspicious lesions should be scored according to PI-RADS V2. The ultrasound-guided transperineal targeted prostate biopsy was performed for those with PI-RADS ≥3 and those with PI-RADS < 3 but tPSA ≥10 ng/ml. The tPSA follow-up examinations were performed every 6 months for tPSA < 10 ng/ml and PI-RADS < 3 points and once a year for tPSA < 4 ng/ml.Results:Among the 16 007 male population ≥50 years, 2 007(12.54%) were found serum PSA ≥4 ng/ml, and 634(31.59%)were referred to the referral hospital through the medical community system. Combining tPSA and mpMRI, 271 patients underwent ultrasound-guided transperineal targeted prostate biopsy. Among them, 162 were finally diagnosed with PCa, with a biopsy positive rate of 59.78%. The detection rate of PCa in all the subjects was 1.01%. According to the pathological grade, 5(3.08%) were in ISUP group 1, 95(58.64%) in ISUP group 2-3, and 62(38.27%) in ISUP group 4-5. There were 102(62.96%), 39(24.07%) and 21(12.96%) with localized, locally advanced or metastatic PCa, respectively. The levels of tPSA in the four groups were (1.13±1.44)ng/ml, (1.77±3.45)ng/ml, (3.27±17.58)ng/ml, and (4.26±11.48)ng/ml, respectively, with statistically significant differences ( P<0.01). The positive number of biopsy in each group was 1 case(0.06%), 56 cases(0.79%), 81 cases(1.36%) and 24 cases(1.82%) respectively, with statistically significant differences ( P<0.01). The number of ISUP 4-5 grades in each group was 0, 17(30.35%), 29(35.80%), and 16(66.67%) respectively, with statistically significant differences ( P<0.01). Conclusions:Based on the medical community system, according to the tPSA screening results of the primary hospitals, it is feasible and effective to refer suspicious patients to the referral hospitals for mpMRI examination, and screen prostate cancer by ultrasound-guided transperineal prostate fusion biopsy.

Objective:To evaluate the safety and efficiency of robotic visualization system(RVS)-assisted microsurgical re-construction of the reproductive tract in male rats and the satisfaction of the surgeons.Methods:We randomly divided 8 adult male SD rats into an experimental and a control group,the former treated by RVS-assisted microsurgical vasoepididymostomy(VE)or vaso-vasostomy(VV),and the latter by VE or VV under the standard operating microscope(SOM).We compared the operation time,me-chanical patency and anastomosis leakage immediately after surgery,and the surgeons'satisfaction between the two groups.Results:No statistically significant difference was observed the operation time between the experimental and the control groups,and no anasto-mosis leakage occurred after VV in either group.The rate of mechanical patency immediately after surgery was 100％in both groups,and that of anastomosis leakage after VE was 16.7％in the experimental group and 14.3％in the control.Compared with the control group,the experimental group achieved dramatically higher scores on visual comfort(3.00±0.76 vs 4.00±0.53,P＜0.05),neck/back comfort(2.75±1.16 vs 4.38±1.06,P＜0.01)and man-machine interaction(3.88±1.55 va 4.88±0.35,P＜0.05).There were no statistically significant differences in the scores on image definition and operating room suitability between the two groups.Conclusion:RVS can be used in microsurgical reconstruction of the reproductive tract in male rats and,with its advantages over SOM in ergonomic design and image definition,has a potential application value in male reproductive system micosurgery.