Objective To investigate the effect of bone metabolic markers on sarcopenia in elderly patients with type 2 diabetes mellitus (T2DM). Methods A total of 412 patients with T2DM in the department of endocrinology of Nanjing Central Hospital from May 2020 to June 2025 were selected as the research subjects. According to Asian Working Group for Sarcopenia (AWGS) in 2019, these patients were evaluated for skeletal muscle mass index (ASMI), muscle strength, and muscle function, and were divided into a sarcopenia group (84 cases) and a non-sarcopenia group (328 cases). The glucolipid metabolic indexes were detected in both groups of patients, and the bone metabolic markers were evaluated, including procollagen type 1 N-terminal peptide (P1NP), beta-C-terminal telopeptide of type 1 collagen (β-CTX), and 25-hydroxy vitamin D [25-(OH)D]. The factors influencing the occurrence of sarcopenia in T2DM patients were analyzed by logistic regression analysis, and the diagnostic values of bone metabolic markers on sarcopenia in patients with T2DM were assessed by ROC curve. Results The levels of P1NP and 25-(OH)D were lower, while β-CTX level was higher in the sarcopenia group compared to the non-sarcopenia group, with statistical differences (P<0.05). After logistic correlation analysis, it was found that P1NP, β-CTX and 25-(OH)D were all influencing factors for the occurrence of sarcopenia in T2DM patients. ROC curve analysis suggested that combined detection of PINP, β-CTX, and 25-(OH)D had higher diagnostic value, with an area under the curve up to 0.805. Conclusion The abnormal expression of bone metabolic markers is associated with the increased risk of sarcopenia in patients with T2DM. The detection of serum bone metabolic markers expression level is of certain significance for the assessment of diabetes-related sarcopenia.

AIM:To evaluate the optimal timing of preoperative intravitreal anti vascular endothelial growth factor(VEGF)therapy in proliferative diabetic retinopathy(PDR)using intraoperative fluorescein angiography(IOFA).METHODS:A retrospective case series study was conducted on patients who underwent vitrectomy for PDR with vitreous hemorrhage(VH)at Sichuan Provincial People's Hospital from January 2023 to February 2025. Patients were divided into three groups according to the interval between intravitreal conbercept injection and surgery: Group A(3 d before surgery), Group B(7 d before surgery), and Group C(14 d before surgery). IOFA was used to assess the number and size of retinal neovascularization(NV). Additional data were collected including preoperative best corrected visual acuity(BCVA), vitreous hemorrhage grading, operative time, frequency of intraoperative endodiathermy, duration of high perfusion pressure, vitreoretinal adhesion grade, postoperative BCVA, and central macular thickness(CMT). Multidimensional analyses were performed.RESULTS:This study enrolled a total of 91 patients(94 eyes)with PDR accompanied by vitreous hemorrhage. Among them, Group A consisted of 31 patients(31 eyes; 18 males, 13 females; mean age 53.26±12.38 y), Group B consisted of 34 patients(37 eyes; 21 males, 13 females; mean age 51.61±14.16 y), and Group C consisted of 26 patients(26 eyes; 18 males, 8 females; mean age 51.00±12.02 y), with baseline characteristics comparable among the three groups(all P>0.05). Comparative analysis of NV visualized via IOFA revealed that both the number and size of NVs were significantly lower in Groups B and C than in Group A(all P<0.0167), while no statistically significant differences were observed between Groups B and C(both P>0.05). No significant differences were found among the three groups regarding other intraoperative parameters, including operation time, frequency of electrocoagulation application, duration of high perfusion pressure, or grading of vitreoretinal adhesion(all P>0.05).CONCLUSION:IOFA confirms that preoperative anti-VEGF therapy administered 7 or 14 d before surgery is more effective than a 3 d interval in suppressing retinal NV activity in PDR patients.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

Machado-Joseph disease, or spinocerebellar ataxia type 3 (SCA3), represents the most common autosomal dominant cerebellar ataxia worldwide. Despite its progressive and debilitating nature, disease-modifying therapies remain elusive. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive intervention; however, its clinical application has been hindered by inconsistent protocols and a lack of mechanistic understanding. A recent landmark study published in Brain Stimulation by Chen et al. addressed these challenges by combining a high-dose intermittent theta-burst stimulation (iTBS) protocol with concurrent transcranial magnetic stimulation-electroencephalography (TMS-EEG). This commentary provides an in-depth analysis of their findings, highlighting the restoration of cerebello-cortical inhibition (CBI) as a key therapeutic mechanism. Furthermore, we discuss the broader implications of this work, proposing that future translational research should integrate accelerated iTBS (aiTBS) paradigms, cortical response measurements (CRM), and individualized neuro-navigation to establish a new era of precision neuromodulation for ataxia.

OBJECTIVE To investigate the effects of subanesthetic dose of esketamine on postoperative anxiety and recovery in patients undergoing laparoscopic cholecystectomy. METHODS A total of 200 patients scheduled for laparoscopic cholecystectomy at Suzhou Ninth Hospital Affiliated to Soochow University from January 2023 to December 2024 were randomly assigned to control group （n＝100） and observation group （n＝100）. One minute before the initiation of anesthesia， patients in the control group received intravenous injections of Propofol emulsion injection， Sufentanil citrate injection， and Succinylcholine chloride injection. On this basis， patients in the observation group received an intravenous injection of Esketamine hydrochloride injection. The anxiety status of patients in both groups was compared， along with their general intraoperative conditions （including sufentanil dosage， duration of pneumoperitoneum， operative time， anesthesia time， and extubation time）， postoperative recovery， incidence of adverse reactions， and the need for dezocine rescue analgesia. Heart rate and mean arterial pressure， entropy index （state entropy and response entropy）， inflammatory marker levels [interleukin-6 （IL-6） and C-reactive protein （CRP）]， numerical rating scale （NRS） for pain intensity were compared between the two groups at different time points. RESULTS No significant differences were found between the two groups in pneumoperitoneum duration， operative time， anesthesia time，extubation time， incidence of postoperative dry mouth， entropy index or length of stay in the post-anesthesia care unit （P＞0.05）. Compared with the control group， the observation group showed significantly lower postoperative STAI-S scores， reduced intraoperative sufentanil consumption， decreased incidence of postoperative nausea， vomiting， and shivering， the need for dezocine rescue analgesia， as well as lower plasma IL-6 and CRP levels at 24 h after surgery， and NRS （P＜0.05）. The heart rate and mean arterial pressure of patients in the observation group at the start of surgery， end of surgery， and during extubation were all significantly higher than those in the control group （P＜0.05）. CONCLUSIONS Subanesthetic dose of esketamine can effectively alleviate postoperative anxiety， reduce intraoperative opioid consumption， suppress postoperative inflammatory response， relieve postoperative pain， and promote recovery in patients undergoing laparoscopic cholecystectomy.

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.

Objective To investigate the relationship between plasminogen activator inhibitor-1(PAI-1)and mean platelet volume/platelet count ratio(MPV/PLT)with infarct size and cerebral artery stenosis in pa-tients with cerebral infarction.Methods A total of 136 patients with cerebral infarction admitted the hospital from January 2022 to January 2024 were selected as observation group,and another 136 healthy individuals who underwent health check-ups were concurrently selected as control group.136 patients with cerebral in-farction were divided into small infarction group,medium infarction group,and large infarction group based on the infarct size.They were also divided into mild stenosis group,moderate stenosis group,severe stenosis group,and occlusion group based on cerebral artery stenosis degree.PAI-1 level was determined using enzyme-linked immunosorbent assay.Mean platelet volume and platelet count ratio were analyzed by fully automated hematology analyzer,and MPV/PLT was calculated.PAI-1 and MPV/PLT were compared among groups.Then receiver operating characteristic(ROC)curve was plotted to evaluate the value of PAI-1 and MPV/PLT in the diagnosis of cerebral infraction,and the correlation of PAI-1 and MPV/PLT with infarct size and cere-bral artery stenosis degree in patients with cerebral infarction was verified using Spearman correlation analy-sis.Results PAI-1 and MPV/PLT were elevated in observation group compared to control group(P＜0.05).ROC curve analysis yielded that the area under the curve(AUC)of single detection of PAI-1 and MPV/PLT in the diagnosis of cerebral infarction was 0.820(95％CI:0.768-0.873)and 0.754(95％CI:0.695-0.814),while the combined detection of the two reached an AUC of 0.896(95％CI:0.853-0.938).The ser-um PAI-1 level and MPV/PLT in the large infarction group were higher than those in the medium infarction group and small infarction group(P＜0.05),and the levels of the above indicators in the medium infarction group were higher than those in the small infarction group(P＜0.05).The serum PAI-1 level and MPV/PLT in the occlusion group were higher than those in the severe stenosis group,moderate stenosis group and mild stenosis group(P＜0.05),the levels of the above indicators in the severe stenosis group were higher than those in the moderate stenosis group and mild stenosis group(P＜0.05),and the levels of the above indicators in the moderate stenosis group were higher than those in the mild stenosis group(P＜0.05).Spearman corre-lation analysis yielded that PAI-1 and MPV/PLT were positively correlated with infarct size and cerebral ar-tery degree stenosis in patients with cerebral infarction(P＜0.05).Conclusion Patients with cerebral infarc-tion have abnormally elevated PAI-1 and MPV/PLT,and the two indicators are closely correlated with infarct size and cerebral artery stenosis,which have significant potential value in early diagnosis,treatment,and dis-ease assessment of diseases.

To evaluate the clinical efficacy of selective fetal reduction in the first trimester for the treatment of intrauterine pregnancy combined with cesarean scar pregnancy (CI-CSP), this article reports a 41-year-old pregnant woman diagnosed with CI-CSP after assisted reproductive technology. At 6 + weeks of gestation, mechanical fetal reduction surgery was performed under ultrasound guidance to eliminate the fetus at the scar site, and the fetal reduction was successful. The pregnancy lasted until 38 weeks of gestation. A healthy male infant was delivered by cesarean section. This case suggests that selective fetal reduction surgery can be a feasible option to preserve intrauterine pregnancy and reduce the risk of CI-CSP, but the indications and perioperative management need to be strictly controlled.

Objective To quantify the intraretinal fluid(IRF)volume in patients with diabetic macular edema(DME)using a deep learning-based three-dimensional segmentation model and to investigate the relationship of IRF volume with visual function and retinal biomarkers based on optical coherence tomography(OCT).Methods A total of 37 pa-tients(42 eyes)with DME who received treatment in the Ophthalmology Department of Sichuan Provincial People's Hospi-tal from July 2022 to September 2024 were prospectively included in this study.A three-dimensional segmentation model was used to automatically quantify the IRF volume within a 6 mm × 6 mm OCT scan at baseline and at the last follow-up.The correlation of visual acuity with IRF volume,central subfield thickness(CST),disorganization of the retinal inner lay-ers(DRIL),hyperreflective foci(HRF),external limiting membrane(ELM),ellipsoid zone(EZ),and vitreomacular in-terface abnormality(VMIA)was analyzed at baseline and the last follow-up.Additionally,the correlation of IRF volume with CST,DRIL,HRF,ELM,EZ,and VMIA was analyzed at both time points.Furthermore,the correlation of the visual acuity at the last follow-up with the IRF volume,CST,DRIL,HRF,ELM,EZ,and VMIA at baseline was analyzed.Results Compared with the baseline value,patients exhibited a significant increase in the best corrected visual acuity(BCVA)(logMAR),a significant decrease in the IRF volume and CST,a significant reduction in the HRF,a significant re-covery in the DRIL,ELM,and EZ(all P＜0.05),and no significant changes in the VMIA(P=1.000)at the last follow-up.At baseline,the BCVA was negatively correlated with the IRF volume,CST,DRIL,and HRF,but positively correlated with the ELM and EZ(all P＜0.05);there was no correlation between the BCVA and VMIA(P=0.069).At the last follow-up,the BCVA was negatively correlated with the DRIL,HRF,and VMIA,but positively correlated with the ELM and EZ(all P＜0.01);the BCVA did not correlate with the IRF volume and CST(P=0.419 and 0.994).At baseline,the IRF volume was positively correlated with the CST(P＜0.001)but negatively correlated with the ELM and EZ(P＜0.01);the IRF vol-ume did not correlate with the DRIL,HRF,and VMIA(all P＞0.05).At the last follow-up,the IRF volume was positively correlated with the CST and HRF(all P＜0.01);however,it was not correlated with the DRIL,ELM,EZ,and VMIA(all P＞0.05).The BCVA at the last follow-up was positively correlated with the BCVA,ELM,and EZ at baseline,but negative-ly correlated with the IRF volume,CST,DRIL,HRF,and VMIA at baseline(all P＜0.05).Conclusion The baseline IRF volume in DME patients is an important influencing factor of visual acuity at baseline and the last follow-up.Hence,the IRF volume may serve as a potential biomarker in the management of DME.

Objective To investigate the effect of epifriedelanol(Epi)on gene expression of P-glycoprotein(P-gp)in human colorectal adenocarcinoma cell line LS174T and its mechanism.Methods LS174T cells were divided into control group and experimental-L,-M,-H groups.Experimental-L,-M,-H groups were treated with 5,10,20 μmol·L-1 Epi,respectively.Control group was treated with 0.1％dimethyl sulfoxide.Polymerase chain reaction was used to detect the mRNA expression level of P-gp.Theeffect of Epi on multidrug resistance protein 1(MDR1/P-gp)luciferase activity was investigated by pregnane X receptor(PXR)-MDR1/P-gp dual luciferase reporter gene assay.In addition,Western Blot was used to detect the protein expression level of P-gp and the nuclear factor-κB(NF-κB)pathway related proteins.Results The relative expression levels of P-gp mRNA in experimental-M,-H groups and control group were 52.24±5.19,23.00±3.52 and 100.00±9.00;the relative expression levels of P-gp protein were 86.37±9.96,74.85±15.92 and 100.00±12.91;the relative activities P-gp luciferase were 230.19±41.32,203.10±52.84 and 279.67±19.20;the relative expression levels of p65(RelA/p65)in nucleus were 132.36±23.93,145.96±25.15 and 100.00±10.88;the relative expression levels of phosphorylation NF-κB inhibits protein kinase α/β(p-IKKα/β)in cytoplasm were 184.00±54.82,290.10±49.59 and 100.00±15.34;the relative expression levels of phosphorylated NF-κB inhibitory protein α(p-IκBα)in cytoplasm were 125.73±18.77,133.69±20.25 and 100.00±8.12;the relative expression levels of IκBα in cytoplasm were 78.36±14.83,70.44±14.57 and 100.00±22.82,respectively.The above indexes of experimental-M and experimental-H groups were compared with control group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Epi can down-regulate the gene expression of P-gp in human colorectal adenocarcinoma cell line LS174T,and the mechanism may be related to activation of NF-κB and suppression of PXR.