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.

ObjectiveTo investigate the clinical efficacy and safety of Qihuang Jianpi Zishen granules in the treatment of cardiac involvement in systemic lupus erythematosus （SLE）. MethodA total of 62 SLE patients with cardiac involvement treated in the Department of Rheumatology and Immunology， the First Affiliated Hospital of Anhui University of Chinese Medicine from June 2021 to December 2022 were randomized into control and observation groups （n=31）. The control group was treated with methylprednisolone tablets and hydroxychloroquine sulfate tablets， and the observation group with Qihuang Jianpi Zishen granules on the basis of the therapy in the control group. After 12 weeks of treatment， the two groups were compared in terms of the therapeutic effect， cardiac function indicators ［left atrial end-diastolic diameter （LADd）， left ventricular end-diastolic diameter （LVDd）， left ventricular posterior wall thickness （LVPWTd）， peak blood flow velocity in early diastolic period （peak E）， peak blood flow velocity in late diastolic period （peak A）， E/A ratio， stroke volume （SV）， left ventricular ejection fraction （LVEF）， left ventricular short axis shortening rate （LVFS）， and B-type natriuretic peptide （BNP）］， vascular damage indicators ［nitric oxide （NO）， endothelin-1 （ET-1）， vascular endothelial growth factor （VEGF）， and homocysteine （Hcy）］， inflammation indicators ［erythrocyte sedimentation rate （ESR） and hypersensitive C-reactive protein （Hs-CRP）］， anti-double-stranded DNA （dsDNA） antibodies， disease activity index （SLEDAI） score， mitigation of symptoms and signs， and occurrence of adverse reactions. ResultThe total response rate in the observation group was 87.09%， which was higher than that （67.74%） in the control group （P<0.01）， and the incidence of adverse reactions had no significant difference between the two groups. After treatment， the control group showed lowered LVDd， LVPWTd， BNP， ET-1， VEGF， and Hcy （P<0.05） and increased E peak， E/A ratio， SV， LVEF， and LVFS （P<0.05）. In the observation group， LADd， LVDd， LVPWTd， peak A， BNP， NO， ET-1， VEGF， and Hcy decreased （P<0.05）， while peak E， E/A ratio， SV， LVEF and LVFS increased （P<0.05） after treatment. The treatment in both groups decreased the scores of palpitation， chest tightness， dyspnea， and edema （P<0.05）， reduced ESR， Hs-CRP， ds-DNA， and SLEDAI （P<0.05）. After treatment， the observation group had lower LADd， LVDd， LVPWTd， peak A， BNP， and scores of palpation， chest tightness， dyspnea， and edema （P<0.05） and higher peak E， E/A ratio， SV， LVEF， and LVFS （P<0.05） than the control group. In addition， the observation group had lower NO， ET-1， VEGF， Hcy， ESR， Hs-CRP， ds-DNA， and SLEDAI than the control group （P<0.05）. ConclusionQihuang Jianpi Zishen granules combined with hydroxychloroquine sulfate and methylprednisolone can improve multiple indicators and mitigate the symptoms and signs of SLE patients with cardiac involvement， demonstrating a clinical application value.

BACKGROUND: The formation of an inhibitory inflammatory microenvironment after spinal cord injury (SCI) remains a great challenge for nerve regeneration. The poor local microenvironment exacerbates nerve cell death; therefore, the reconstruction of a favorable microenvironment through small-molecule drugs is a promising strategy for promoting nerve regeneration. METHODS: In the present study, we synthesized curcumin-loaded micelle nanoparticles (Cur-NPs) to increase curcumin bioavailability and analyzed the physical and chemical properties of Cur-NPs by characterization experiments. We established an in vivo SCI model in rats and examined the ability of hind limb motor recovery using Basso–Beattie– Bresnahan scoring and hind limb trajectory assays. We also analyzed neural regeneration after SCI using immunofluorescence staining. RESULTS: The nanoparticles achieved the intelligent responsive release of curcumin while improving curcumin bioavailability. Most importantly, the released curcumin attenuated local inflammation by modulating the polarization of macrophages from an M1 pro-inflammatory phenotype to an M2 anti-inflammatory phenotype. M2-type macrophages can promote cell differentiation, proliferation, matrix secretion, and reorganization by secreting or expressing pro-repair cytokines to reduce the inflammatory response. The enhanced inflammatory microenvironment supported neuronal regeneration, nerve remyelination, and reduced scar formation. These effects facilitated functional repair in rats, mainly in the form of improved hindlimb movements. CONCLUSION Here, we synthesized pH/temperature dual-sensitive Cur-NPs. While improving the bioavailability of the drug, they were also able to achieve a smart responsive release in the inflammatory microenvironment that develops after SCI. The Cur-NPs promoted the regeneration and functional recovery of nerves after SCI through anti-inflammatory effects, providing a promising strategy for the repair of SCIs.

Objective:To construct future-oriented theoretical management model for medical quality and patient safety.Methods:Procedure grounded theory was applied to code data including 30 expert interview records from July 2021 to June 2022 and the qualitative analysis results of 71 core literatures in Chinese and English, and then the theoretical model was constructed.Results:After three-level coding, 555 reference points, 249 initial concepts, 41 categories, 27 main categories and 7 core categories related to medical quality and safety management were sorted out, and the theoretical model of SQ (I-SPORT) matrix for medical quality and safety management was constructed. This model extended the traditional dimension in quality and safety management.Conclusions:Regarding medical quality and safety management, on one hand, should focus on the systematic improvement of structure, process, results, reengineering, education and training in terms of management functions; on the other hand, it is necessary to improve the organization, employees, resources, technology and tools, and patient experience in terms of management elements.

Objective:To explore the features of atherosclerotic plaque in patients with type 2 diabetes mellitus by contrast-enhanced ultrasound (CEUS), and to analyze the correlation between the features and leukocyte count in peripheral blood.Methods:A total of 30 type 2 diabetic patients with carotid atherosclerotic plaque treated in Tangdu Hospital of Air Force Military Medical University who underwent CEUS from March 2018 to September 2021 were included as the diabetes group. Thirty-two non-diabetic patients with carotid atherosclerotic plaque who were matched for age and sex during the same period served as the control group. The optimized plaques were performed by CEUS to obtain parameters including peak (P), time to peak (TP), sharpness (S) and area under the curve (AUC) of time-intensity gamma fitting curve (FC curve). The differential count of leukocytes in peripheral blood was detected by the automatic hematology analyzer. Spearman rank correlation and multiple linear regression were used to analyze the correlation between CEUS parameters of plaque and the differential leukocyte count in peripheral blood.Results:①The peripheral blood leukocyte count, monocyte count and monocyte proportion in the diabetes group were higher than those in the control group (all P<0.05). ②P and AUC in the diabetes group were higher than those in the control group (all P<0.05). ③There was linear relationship( B=75.440, P<0.001) and positive correlation ( rs=0.929) between P and peripheral blood monocyte count in the diabetes group. Conclusions:The neovascularization density and perfusion in carotid plaques in patients with type 2 diabetes mellitus are increased, which may be related to the increase of leukocytes in circulation, especially monocytes.

Objective:To assess the efficacy and safety of 100 units of botulinum toxin A (BTX-A) intradetrusor injection in patients with overactive bladder.Methods:From April 2016 to December 2018, 17 tertiary hospitals were selected to participate in this prospective, multicenter, randomized, double-blind, placebo-controlled study. Two phases of study were conducted: the primary phase and the extended phase. This study enrolled patients aged 18 to 75 years who had been inadequately managed by anticholinergic therapy (insufficient efficacy or intolerable side effects) and had spontaneous voiding with overactive bladder. Exclusion criteria included patients with severe cardiac, renal and hepatic disorders, patients with previous botulinum toxin treatment for 6 months or allergic to BTX-A, patients with urinary tract infections, patients with urinary stones, urinary tract tumors, diabetes mellitus, and bleeding tendency. Eligible patients were randomly assigned to BTX-A group and placebo control group in a ratio of 2∶1. Two groups of patients received 20 intradetrusor injections of BTX-A 100U or placebo at the depth of the submucosal muscle layer respectively under cystoscope, including 5 injections at the base of the bladder, 3 injections to the bladder triangle, 5 injections each to the left and right walls and 2 injections to the top, sparing the bladder neck. As a placebo control group, patients received same volume of placebo containing no BTX-A and only adjuvant freeze-dried preparations for injection with the same method. A combination of gelatin, sucrose, and dextran served as adjuvants. Average micturition times per 24 hours, urinary incontinence (UI) episodes per day, average micturition volume per day, OAB symptom score(OABSS), and quality of life (QOL) score were recorded at baseline and the 2nd, 6th and 12th week after treatment. The primary efficacy endpoint was the change from baseline in the average micturition times per 24 hours at the 6th week after treatment. The secondary efficacy endpoints included the change from baseline in the average micturition times per 24 hours at 2nd and 12th week, as well as the change from baseline in the OABSS, QOL score, average frequency of urgency and UI episodes per day, urgency score, average micturition volume per day at 2nd, 6th and 12th week after treatment. Patients were followed for 12 weeks to assess adverse events (AEs). After assessed at week 12, if the micturition times has decreased less than 50% compared to baseline and the patient is willing to receive retreatment, then patients could enter the extended trial phase. In that phase, patients in both groups were injected with 100 units BTX-A from 12th week onwards and then followed up the same indicators for 12 weeks.Results:216 patients were enrolled in this trial (144 cases in the BTX-A group and 72 cases in the placebo control group). Baseline characteristics such as age (47.75±14.20 in the BTX-A group and 46.39±15.55 in the control group), sex (25 male/117 female in the BTX-A group and 10/61 in the control group), and disease duration (0.51 years in the BTX-A group and 0.60 years in the control group) were balanced between the two groups( P>0.05). A marked reduction from baseline in average micturition times per 24 hours was observed in all treatment groups at the 6th week and the reduction of the two groups was statistically different ( P<0.001 and P=0.008 respectively). Compared with the baseline, the average micturition times per 24 hours at the 6th week decreased from baseline by 2.40(0.70, 4.60)times for the BTX-A group and 0.70(-1.00, 3.30) times for the placebo control group respectively, and the difference between the two groups was considered to be statistically significant ( P=0.003). The change rates of average micturition times per 24 hours from baseline at the 6th week of the two groups were (16±22)% and (8±25)% respectively, and the difference between the two groups was statistically significant ( P=0.014). Compared with the baseline, the average micturition times per 24 hours at 2nd and 12th week decreased by 2.00(0.00, 4.00)and 3.30(0.60, 5.03)for the BTX-A group, 1.00(-1.00, 3.00)and 1.70(-1.45, 3.85)for the placebo control group respectively. The difference between two groups was considered to be statistically significant ( P=0.038 and P=0.012); the changes of average urgency times per day for the BTX-A group and the control group at the 2nd, 6th and 12th week were 2.00(0.00, 4.30)and 2.40(0.30, 5.00), 3.00(0.30, 5.70)and 0.70(-1.30, 2.70), 0.70(-1.30, 3.00) and 1.35(-1.15, 3.50), respectively. There were significant differences between two groups at the 2nd, 6th and 12th week, ( P=0.010, P=0.003 and P=0.025, respectively). The OABSS of the BTX-A group and the control group at the 6th week decreased by 1.00(0.00, 4.00)and 0.50(-1.00, 2.00) compared with the baseline, and the difference between the two groups was statistically significant ( P=0.003). 47 cases of BTX-A group and 34 cases of placebo control group entered the extended trial phase, and 40 and 28 cases completed the extended trial phase, respectively. The average micturition volume per 24 hours changed by -16.60(-41.60, -0.60)ml and -6.40(-22.40, 13.30)ml, (-35.67±54.41)ml and(-1.76±48.69)ml, (-36.14±41.51)ml and (-9.28±44.59)ml, (-35.85±43.35)ml and(-10.41±40.29)ml for two groups at the 12th, 14th, 18th and 24th week, and the difference between two groups was statistically significant at each follow-up time ( P=0.01, 0.006, 0.012 and 0.016, respectively). There was no significant difference in other parameters( P>0.05). However, adverse reactions after intradetrusor injection included increased residual urine volume (27 in the BTX-A group and 3 in the control group), dysuria (21 in the BTX-A group and 6 in the control group), urinary infection (19 in the BTX-A group and 6 in the control group), bladder neck obstruction (3 in the BTX-A group and 0 in the control group), hematuria (3 in the BTX-A group and 1 in the control group), elevated alanine aminotransferase (3 in the BTX-A group and 0 in the control group), etc. During the follow-up period, there was no significant difference in the other adverse events between two groups except the increase of residual urine volume( P<0.05). In the primary trial phase, among the 27 cases with increased residual urine volume in BTA group, only 1 case (3.70%) with PVR more than 300 ml; the PVR of 3 patients in the placebo group was less than 100 ml. The increase of residual urine volume caused by the injection could be improved or disappeared with the passage of time. Conclusions:Intradetrusor injection of Chinese BTX-A improved the average micturition times per 24 hours, the average daily urgent micturition times, OABSS, and average micturition volume per time, and reduced the adverse effects in patients with overactive bladder.Chinese BTX-A at dose of 100U demonstrated durable efficacy and safety in the management of overactive bladder.

Objective: To explore the effectiveness and safety of ultrasound-guided radiofrequency ablation (RFA) in treatment of thyroid benign nodules. Methods: We analyze 573 patients with thyroid benign nodules from June 2014 to September 2017 treated by RFA at Department Ⅱof Thyroid Surgery, the First Affiliated Hospital of Zhengzhou University. Among these patients, there were 75 males and 498 females, with a median age of 45 years old. All patients were diagnosed as thyroid benign nodules by ultrasound-guided fine needle aspiration biopsy before RFA. A total of 750 benign tumors were treated. To evaluate the thyroid function of the patients before RFA and 3 months after it, and to observe the changes of thyroid benign nodules by ultrasound at 3, 6, 12 months after RFA. The paired t-test was used to compare the measurement data with normal distribution, and Wilcoxon's signed rank test was used to compare the measurement data with non-normal distribution. To calculate the volume change and reduction rate of thyroid benign nodules. Results: RFA was successfully completed in all patients, the volume reduction rate was 67%(48%, 83%) in the 3rd month after RFA, in the 6th month was 81%(67%, 91%), in the 12th month was 89%(80%, 95%). Eighteen patients felt pain during RFA, but the pain was alleviated after stopping ablation. Three patients′ tone decreased, but recovered in a week. Hoarseness occurred in 6 patients and recovered in 3 months. Three patients had neck hemorrhage, which was managed with simple compression of the neck. Conclusions RFA is an effective and safe treatment for thyroid benign nodules and has obvious advantages such as less invasiveness, having no influence in thyroid functions. It is clinically prospective for application.

Purpose The mean pulmonary artery (MPAP) has been widely used as an important parameter to diagnose and evaluate pulmonary hypertension (PH).The purpose of this paper is to compare the efficacy of two methods in evaluating PH,including estimating pulmonary artery systolic pressure (PASP) using Doppler ultrasonography to measure tricuspid regurgitation (TR) velocity,and directly using the peak velocity of TR.Materiasl and Methods From January 2012 to June 2013,eighty patients with left-to-right shunt congenital heart diseases (CHD) planned for closure procedure in Tangdu Hospital of the Fourth Military Medical University and the General Hospital of Shenyang Military region were included in this prospective study,who underwent right heart catheterization to measure pulmonary artery pressure,and underwent Doppler ultrasonography to measure the peak velocity ofTR.Results Using catheter-measured MPAP of≥ 25 mmHg as diagnostic reference,the false positive rate was 62.96％,and the false negative rate 0％ when the estimated PASP of ＞30 mmHg determined by TR method was used to diagnose PH.There was high diagnostic agreement when peak velocity of TR was used to diagnose PH.When 320 cm/s and 340 crn/s were used as diagnostic cutoff values,false positive rates were 14.81％ and 7.41％,and false negative rates were 15.91％ and 20.45％,respectively.Conclusion In patients with left-to-right shunt CHD,peak velocity of TR measured on echocardiography can be used to diagnose PH which overcomes the high false positive rate in estimation method.It is more suitable to diagnose PH when the MPAP is used as the diagnostic criterion.

Objective To evaluate the relationship between endothelin-1 (ET-1) and p38 mitogenactivated protein kinase (p38 MAPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathways during mechanical stretch-induced enhancement of adhesion of rat pulmonary microvascular endothelial cells (PMVECs).Methods Rat PMVECs were seeded in the culture plate at a density of 0.5×105 cells/ml (2 ml/well) and divided into 5 groups (n=24 each) using a random number table:control group (group C),mechanical stretch group (group MS),mechanical stretch plus specific PI3K inhibitor LY294002 group (LY group),mechanical stretch plus specific p38 MAPK inhibitor SB203580 group (SB group),and mechanical stretch plus selective ETA receptor blocker BQ123 group (BQ group).Cells were exposed to 20％ cyclic stretch at 0.3 Hz for 4 h using a sine wave.In LY,SB and BQ groups,LY294002,SB203580 and BQ123 at the final concentration of 10 μmol/L were added,respectively,after mechanical stretch,cells were incubated for 10 min,and then extracted and purified rat polymorphonuclear neutrophil leukocytes (PMNs,5× 105 cells/well) were added and co-incubated with PMVECs for 30 min and then washed out.The concentrations of ET-1 and interleukin-6 (IL-6) in the culture medium were determined using enzyme-linked immunosorbent assay.The expression of phosphorylated p38 MAPK (p-p38 MAPK) and phosphorylated Akt (p-Akt) was detected by Western blot.Adhesion of PMNs was measured by immuno-histochemistry,and the adhesion rate was calculated.The expression of P-selectin mRNA was detected using real-time polymerase chain reaction.Results Compared with group C,the concentrations of IL-6 and ET-1 in the culture medium were significantly increased,the expression of p-p38 MAPK,p-Akt and P-selectin mRNA was up-regulated,and the adhesion rate of PMNs was increased in the other four groups (P＜0.05).Compared with group MS,the concentration of IL-6 in the culture medium was significantly decreased,the expression of p-Akt and P-selectin mRNA was down-regulated,and the adhesion rate of PMNs was decreased in LY,SB and BQ groups,the concentration of ET-1 in the culture medium was significantly decreased in group BQ,and the expression of p-p38 MAPK was significantly down-regulated in SB and BQ groups (P＜0.05).Conclusion The signaling mechanism underlying ET-1-mediated enhancement of rat PMVEC adhesion may be related to activating p38 MAPK and PI3K/Akt signaling pathways.

Objective To study pulmonary wedge angiography ( PWA ) with hemodynamic the evaluation of children with congenital heart disease and pulmonary artery hypertension ( PAH) . Methods Hemodynamic measurement and pulmonary wedge angiography were performed in 50 children with congenital heart disease. Comparison and analysis were made from the data obtained from PWA and catheterization. Results After PWA, the patients were categorized into 3 groups according to the measured hemodynamics parameters:group A [ n=15, patients with normal mean pulmonary artery pressure ( mPAP≤25 mmHg) and normal pulmonary vessel resistance (PVR﹤300 dyne?s?cm5)], group B [n=24, patients with PAH (mPAP﹥25 mmHg) but normal PVR] and group C (n=11, patients with PAH and elevated PVR (PVR≥300 dyne?s?cm5). Rote of tapering (ROT) was significant lower in group C than in group A and B (F=42. 559,P﹤0. 05). Pulmonary circulation time (PCT) was higher in group C than in group A and B (F=6. 037,P﹤0. 05). ROT correlated negatively with PVR (r = -0. 606, P ﹤0. 05). PCT index correlated positively with PVR (r=0. 783,P=0. 01). There was no significant correlation between PCT and mean pulmonary artery hypertension (mPAP). Conclusions PWA may help to make quantitative analysis of the pulmonary vascular status in patients with congenital heart disease.