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 Using the concept of allostatic load(AL)to evaluate aging of male SD rats and the effectiveness of Zuogui Pill in naturally aging rats.Methods Naturally aging male SD rats were tested at the ages of 2,5,8,14,18,and 21 months.They were divided into an elderly control group,low-dose Zuogui Pill group,and high-dose Zuogui Pill group.Intervention with Zuogui Pill was trialed for 3 months.Blood samples were taken from the tails of rats each month,and the number of T lymphocytes and rate of apoptosis were measured by flow cytometry.Low-density lipoprotein cholesterol(LDL-c),high-density lipoprotein cholesterol(HDL-c),triglycerides(TG),total cholesterol(TC),free fatty acids(FFA),25 hydroxyvitamin D(25-OH-D),corticosterone(CORT),C-reactive protein(CRP),and interleukin-6(IL-6)were detected in rat sera.By identifying the collinearity between indicators and professional considerations,LDL-c,TC,HDL-c,FFA,TG,CORT,IL-6,CRP,25-OH-D,CD3+T cell count,and CD3+T cell apoptosis rate were included in the AL scoring.The threshold for each indicator was established with data from 5-month-old rats,and the score was 1 point below or/and above the threshold.Results The serum levels of LDL-c,TG,TC,25-OH-D,CRP,and IL-6 of rats showed significant changes with age,although the patterns of change differed.The CD3+T lymphocyte count significantly decreased with age(P＜0.01),while the apoptosis rates of CD3+,CD4+,and CD8+T lymphocytes significantly increased with age(P＜0.01).Zuogui Pill significantly increased serum CORT levels in elderly rats(P＜0.01)and reduced the apoptosis rate of CD8+T lymphocytes(P＜0.05).The AL score began to increase in rats at 5 months of age and reached its peak in those of 18 months of age.Conclusions AL can better characterize the aging process compared to a single indicator.Zuogui Pill can improve the stress response ability of aging rats and alleviate immunosenescence.

OBJECTIVE: To study the preparation and properties of the hyaluronic acid (HA)/α-calcium sulfate hemihydrate (α-CSH)/β-tricalcium phosphate (β-TCP) material (hereinafter referred to as composite material). METHODS: Firstly, the α-CSH was prepared from calcium sulfate dihydrate by hydrothermal method, and the β-TCP was prepared by wet reaction of soluble calcium salt and phosphate. Secondly, the α-CSH and β-TCP were mixed in different proportions (10∶0, 9∶1, 8∶2, 7∶3, 5∶5, and 3∶7), and then mixed with HA solutions with concentrations of 0.1%, 0.25%, 0.5%, 1.0%, and 2.0%, respectively, at a liquid-solid ratio of 0.30 and 0.35 respectively to prepare HA/α-CSH/ β-TCP composite material. The α-CSH/β-TCP composite material prepared with α-CSH, β-TCP, and deionized water was used as the control. The composite material was analyzed by scanning electron microscope, X-ray diffraction analysis, initial/final setting time, degradation, compressive strength, dispersion, injectability, and cytotoxicity. RESULTS: The HA/α-CSH/β-TCP composite material was prepared successfully. The composite material has rough surface, densely packed irregular block particles and strip particles, and microporous structures, with the pore size mainly between 5 and 15 μm. When the content of β-TCP increased, the initial/final setting time of composite material increased, the degradation rate decreased, and the compressive strength showed a trend of first increasing and then weakening; there were significant differences between the composite materials with different α-CSH/β-TCP proportion ( P<0.05). Adding HA improved the injectable property of the composite material, and it showed an increasing trend with the increase of concentration ( P<0.05), but it has no obvious effect on the setting time of composite material ( P>0.05). The cytotoxicity level of HA/α-CSH/β-TCP composite material ranged from 0 to 1, without cytotoxicity. CONCLUSION The HA/α-CSH/β-TCP composite materials have good biocompatibility. Theoretically, it can meet the clinical needs of bone defect repairing, and may be a new artificial bone material with potential clinical application prospect.
Calcium Phosphates ; Bone and Bones ; Phosphates

OBJECTIVE: To propose a semi-supervised material quantitative intelligent imaging algorithm based on prior information perception learning (SLMD-Net) to improve the quality and precision of spectral CT imaging. METHODS: The algorithm includes a supervised and a self- supervised submodule. In the supervised submodule, the mapping relationship between low and high signal-to-noise ratio (SNR) data was constructed through mean square error loss function learning based on a small labeled dataset. In the self- supervised sub-module, an image recovery model was utilized to construct the loss function incorporating the prior information from a large unlabeled low SNR basic material image dataset, and the total variation (TV) model was used to to characterize the prior information of the images. The two submodules were combined to form the SLMD-Net method, and pre-clinical simulation data were used to validate the feasibility and effectiveness of the algorithm. RESULTS: Compared with the traditional model-driven quantitative imaging methods (FBP-DI, PWLS-PCG, and E3DTV), data-driven supervised-learning-based quantitative imaging methods (SUMD-Net and BFCNN), a material quantitative imaging method based on unsupervised learning (UNTV-Net) and semi-supervised learning-based cycle consistent generative adversarial network (Semi-CycleGAN), the proposed SLMD-Net method had better performance in both visual and quantitative assessments. For quantitative imaging of water and bone materials, the SLMD-Net method had the highest PSNR index (31.82 and 29.06), the highest FSIM index (0.95 and 0.90), and the lowest RMSE index (0.03 and 0.02), respectively) and achieved significantly higher image quality scores than the other 7 material decomposition methods (P < 0.05). The material quantitative imaging performance of SLMD-Net was close to that of the supervised network SUMD-Net trained with labeled data with a doubled size. CONCLUSIONS A small labeled dataset and a large unlabeled low SNR material image dataset can be fully used to suppress noise amplification and artifacts in basic material decomposition in spectral CT and reduce the dependence on labeled data-driven network, which considers more realistic scenario in clinics.
Tomography, X-Ray Computed/methods* ; Image Processing, Computer-Assisted/methods* ; Algorithms ; Signal-To-Noise Ratio ; Perception

Objective:To explore the correlation between preoperative echocardiography indicators and surgical prognosis of children with ventricular septal defect (VSD) and conduct verification based on significant indicators and indicator ratios.Methods:A total of 1 357 children with VSD who were admitted to the Children′s Hospital, Zhejiang University School of Medicine from June 2016 to June 2021 were selected. Various measurements including the size of the VSD, left ventricular ejection fraction (LVEF), left atrial (LA) diameter, the aortic (AO) flow rate, the tricuspid regurgitation velocity and pressure gradient were extracted from preoperative echocardiography reports. This paper explored the correlation between echocardiography reports indicators, indicator ratios and postoperative auxiliary ventilation time, respectively. The patients were divided into two groups according to whether there were complications, and the differences of echocardiography reports indicators between the two groups were compared. A linear regression model was established to predict the postoperative auxiliary ventilation time using these indicators, and the least absolute shrinkage and selection operator (LASSO) regression model was used for variable selection.Results:The VSD size and AO flow velocity were weakly correlated with the postoperative auxiliary ventilation time ( r=0.32, 0.25; all P<0.01). There was no significant correlation between VSD flow velocity and postoperative auxiliary ventilation time. The AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity were strongly correlated with the postoperative auxiliary ventilation time ( r=0.67, 0.51; all P<0.01). In the significance test, there were no significant differences in tricuspid regurgitation flow velocity, tricuspid regurgitation pressure gradient, LA diameter, and LVEF between the complication group and the non-complication group(all P>0.01). However, the ratio of LVEF/tricuspid regurgitation velocity in the complication group was significantly lower than that in the non-complication group, and the ratio of tricuspid regurgitation pressure gradient/LA diameter was significantly higher than that in the non-complication group (all P<0.01). The postoperative auxiliary ventilation time of VSD patients was predicted on an independent test set, with an R2 of 0.51. Conclusions:Echocardiography report indicator ratios of AO flow velocity/VSD flow velocity and LVEF/VSD flow velocity have strong correlations with postoperative auxiliary ventilation time in children with VSD, and the ratios of LVEF/tricuspid regurgitation velocity and tricuspid regurgitation pressure gradient/LA diameter are significantly different between groups with and without postoperative complications. The ratios of indicators can significantly improve this correlation and difference, which can be used to predict the prognosis of VSD operation.

Objective To study the effect of interlocking intramedullary nail on fixing transverse olecranon fracture. Methods Nine pairs of fresh ulna specimens were collected and the transverse fracture model of olecranon was established. Kirschner wire tension band and interlocking intramedullary nail were used to repair the fracture. Cyclic dynamic tension loads with amplitude of 25 N, mean value of 45 N and frequency of 05 Hz were applied to the triceps tendon under simulated elbow flexion conditions of 30°, 45° and 60°, respectively. The fracture displacements of specimens within 300 cycles were recorded in three groups. ResultsAt 30° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.831±0.333) mm and (3.723±2.390) mm, respectively. At 45° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.167±0.374) mm and (2.455±0.609) mm, respectively. At 60° flexion angle, the fracture displacement of interlocking intramedullary nail group and Kirschner wire tension band group was (1.407±0.342) mm and (3.112±1.025) mm, respectively. The fracture displacement of interlocking intramedullary nail was smaller. Conclusions The mechanical properties of interlocking intramedullary nail are better than those of Kirschner wire tension band, and the interlocking intramedullary nail is more stable and firmer for fixing transverse olecranon fracture. Moreover, the interlocking intramedullary nail is installed with the operating tool, thus the operation is more accurate and faster, and the operation efficiency is greatly improved.

Objective:To investigate the application value of laparoscopic duodenum-preserving pancreatic head resection (LDPPHR).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 25 patients undergoing LDPPHR in the Second Hospital of Hebei Medical University from November 2016 to November 2020 were collected. There were 7 males and 18 females, aged from 14 to 66 years, with a median age of 29 years. All the 25 patients underwent LDPPHR. Observation indicators: (1) surgical situations; (2) postoperative histopathological examination; (3) follow-up. Follow-up was conducted using outpatient examination or telephone interview to detect the recovery of patients up to March 2021. Measurement data with skewed distribution were represented as M (range) and count data were descripted as absolute numbers. Results:(1) Surgical situations: all the 25 patients underwent LDPPHR successfully, including 23 cases undergoing total pancreatic head resection and 2 cases undergoing subtotal pancreatic head resection. The operation time and volume of intraoperative blood loss of 25 patients were 310 minutes (range, 207 to 540 minutes) and 200 mL (range, 50 to 800 mL), respectively. Of the 25 patients, 1 case was infused with 4 U of red blood cells and 400 mL of plasma, 1 case was infused with 500 mL of plasma, 1 case was infused with 600 mL of plasma and the remaining 22 cases were not infused with red blood cells or plasma. Of the 25 patients, 3 cases with pancreatic fistula of class B were discharged after drainage, 4 cases had biliary fistula including 2 cases undergoing symptoms disappeared after implantation of common bile duct stent by endoscopic retrograde cholangiopancreatography, 1 case recovering well with drainage, 1 case with postoperative perihepatic effusion undergoing symptoms disappeared after the treatment of drainage and common bile duct stent implantation, and the remaining 18 cases had no complications. The duration of postoperative hospital stay was 17 days (range, 9 to 27 days) of the 25 patients. (2) Postoperative histopathological examination: the tumor volume of the 25 patients was 6.0 cm×5.0 cm×2.0 cm (range, 1.0 cm×2.0 cm×1.5 cm to 10.0 cm×9.0 cm×8.0 cm). Results of the postoperative histopathological examination showed that there were 12 cases with pancreatic solid pseudopaillary neoplasm, 4 cases with intraductal papillary mucinous neoplasm, 3 cases with serous cystadenoma, 2 cases with mucinous cystadenoma, 1 case with neuroendocrine neoplasm, 1 case with pancreatic true cyst, 1 case with cholesterol crystals combined with calcification in the center of pancreatic nodules and 1 case with cavernous hemangioma of pancreas. (3) Follow-up: all the 25 patients were followed up for 4 months to 48 months, with a median follow-up time of 27 months. During the follow-up, 1 case of the 25 patients with postoperative diabetes controlled blood glucose in the normal range after regular injection of insulin, 1 case with fatty diarrhea had symptoms improved after oral supplement of pancreatic enzyme preparation, 1 case with preoperative intermittent dizziness, weakness of both lower limbs and hypoglycemia had the level of blood glucose returned to normal without any special treatment after operation, and the remaining 23 cases had no metabolic complications. None of the 25 patients had tumor malignant transformation, recurrence or death. No long-term complications such as delayed gastric emptying, bile duct stones or stricture occurred to the 25 patients.Conclusion:LDPPHR is safe and feasible for the treatment of benign or low-grade malignant tumors of the pancreatic head, with the advantage of preserving the integrity of digestive tract.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

Objective: To analyze the efficacy of HLA-haploidentical peripheral hematopoietic stem cell transplantation (haplo-PBSCT) following reduced intensity conditioning (RIC) regimen to treat the patients with hematological malignancies who were older than 50 years old. Methods: Eighteen patients with hematological malignancies over 50 years were enrolled, including 8 male and 10 female patients. The median age of all patients was 52 (range: 50–66) years. Of them, 8 patients had acute myeloid leukemia (AML) , 2 chronic myelocytic leukemia (CML) , 5 myelodysplastic syndrome (MDS) , 2 acute lymphoblastic leukemia (ALL) , and 1 aggressive natural killer cell leukemia (ANKL) . All patients received fludarabine, cytarabine and melphalan with rabbit anti-human thymocyte globulin (FAB+rATG regimen) and transplanted with high dose non-T cell-depleted peripheral hematopoietic stem cells from donors. Enhanced graft versus host disease (GVHD) prophylaxis and infection prevention were administered. Results: Fifteen days after transplantation, 16 patients achieved complete donor chimerism. One of them rejected the donor graft completely at thirty days after transplantation, and the other 2 patients had mixed chimerism 15 days after transplantation and converted to complete recipient chimerism at 30 days after transplantation. The cumulative incidence of acute GVHD (aGVHD) was 61.1% (95%CI49.6%-72.6%) . The incidence of grade Ⅱ-Ⅳ aGVHD was 35.4% (95%CI 21.1%-49.7%) , whereas grade III-IV was 13.8% (95%CI 4.7%-22.9%) . The 2-year cumulative incidence of chronic GVHD (cGVHD) rate was estimated at 38.2% (95%CI 25.5%-50.9%) . Patients were followed-up for a median of 14.5 months (range, 3-44 months) . The Kaplan Meier estimates of 2-year overall survival (OS) and disease-free survival (DFS) was 72.6% (95%CI 60.1%-85.1%) and 63.7% (95%CI 49.2%-78.2%) , respectively. The 2-year cumulative incidence of relapse and non-relapse-mortality (NRM) was 31.2% (95%CI 16.5%-45.9%) and 12.5% (95%CI 4.2%-20.8%) , respectively. Conclusion RIC-haplo-PBSCT protocol can achieve better results in patients with hematologic malignancies over 50 years old.

Objective To explore the value of endoscopic retrograde cholangiopancreatography (ERCP) in patients with choledocholithiasis after Billroth Ⅱ gastrointestinal anastomosis.Methods A retrospective cohort study was conducted to retrospective review the data of 189 patients with choledocholithiasis treated by ERCP from December 2015 to November 2017 in Department of Hepatobiliary Surgery,Second Hospital of Hebei Medical University.According to the history of Billroth Ⅱ gastrointestinal anastomosis,the patients who have not undergone digestive surgery were divided into the normal group(n =167) and patients who have undergone digestive surgery were divided into reconstruction group (n =22).The operation time,the success rate of stone extraction,complications,the hospitalization time,total hospitalization expenses were compared between the two groups.Measurement data with normal distribution were represented as (Mean ± SD) and comparison between groups was analyzed using the t test.Measurement data with skewed distribution were described as M (range).Comparisons of count data were analyzed using the x2 test or Fisher exact probability.Results The operation time of the normal group was (40.18 ± 11.80) min,and the success rate of ERCP was 97.60％ (163/167),the operation time of reconstruction group was(61.81 ± 13.21) min,and the success rate of ERCP was 81.82％ (18/22),There were significant differences between the two groups (t =0.105,x2 =10.400,P ＜ 0.05).The complications,the hospitalization time and the total hospitalization expense of the normal group were 16.17％ (27/167),(3.47 ± 1.55) d,(20 620.69 ± 3 117.88) yuan,the reconstruction group were 18.18％ (4/22),(4.18 ± 2.08) d,(22 426.41 ±5 916.30) yuan,with no statistically significant difference (x2 =0.000,t =4.204),t =10.828,P ＞ 0.05).Conclusions ERCP is safe and feasible for patients with choledocholithiasis after Billroth Ⅱ gastrointestinal anastomosis.It also has a high success rate of stone removal and small trauma,which is worthy of promotion.