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 discuss the repair effect of lyophilized platelet lysate (PL) products on articular cartilage injury model of rats. 【Methods】 A total of 25 SD rats were injected with typeⅡcollagenase at the right knuckle articular cavity respectively on day 1, 3 and 5 of experiment, and the modeling conditions were observed 14 days after the last injection of collagenase. The SD rats with successful modeling were randomly divided into three groups, and were injected with lyophilized PL [Group A, 1 mL/(mouse·time)], PL [Group B, 1 mL/(mouse·time)], and normal saline[Group C, 1 mL/(mouse·time)]. The above three substances were injected with corresponding drugs on day 0, 7, 14 and 21 of experiment based on the grouping conditions, and the changes of knee joint diameters of the rats from the three groups were observed and compared. On day 14 and 28, one rat in each group was randomly killed and two knuckle articular cavities of each were taken for tissue sampling, using hematoxylin-eosin staining (HE) and immunohistochemistry. 【Results】 After 14 days of modeling by injection of type Ⅱ collagenase, the proportion of successful modeling in rats was 84% (21/25), with the knee joint diameter (mm) before and after modeling at 12.84±1.14 vs 14.11±1.17(P<0.01). On day 14, 21 and 28, groups A and B were superior to group C in the knee joint diameter and activity improvement (P<0.05), with 13.33±1.16 vs 13.37±1.08 vs 14.21±1.08, 13.10±1.09 vs 13.01±1.04 vs 14.09±1.09 and 12.38±1.08 vs 12.51±1.03 vs 14.01±1.07, respectively. Histological observation showed that group A and B were superior to group C in the production and arrangement of chondrocytes and the positive expression of type Ⅱ collagen, and there was no significant difference between group A and group B. 【Conclusion】 The lyophilized PL has similar therapeutic effect to PL in the treatment and repair of articular cartilage injury, and is worthy of clinical application.

【Objective】 To explore the clinical effects of autologous platelet-rich plasma (PRP) in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation. 【Methods】 A total of 34 patients with postoperative bone nonunion for long bone shaft fracture, who were admitted and cured in the Orthopedics Department of our hospital from January 2019 to June 2020, were selected. They were randomly divided into the experimental group(n=17) and control group(n=17). Individuals in the control were treated with autologous iliac bone alone., while the experimental group were treated with autologous iliac bone graft plus autologous PRP during and after operation. After surgery, the autogenous PRP was accurately injected with ultrasound guidance every 7 days (5 mL/person, 4 occasions in total). The clinical healing time of the fracture, the grading of callus formation and the functional rehabilitation level of limbs on the affected side at different time were observed in both groups. 【Results】 All 34 patients were followed up. In the experimental group and the control group, the clinical healing time (month) of the fracture was (5.03±1.24) vs (6.91±1.41), P<0.05. The healing rate of the fracture for 6 months and 9 months was 94%(16/17)vs 59%(10/17)and 94%(16/17)vs 82%(14/17), respectively (P<0.05). The grading of callus formation within 3, 6 and 9 months was (2.11±0.69) vs (1.53±0.80), (3.06±0.90) vs (2.59±0.87) and (3.82±0.73) vs (3.35±0.86), respectively (P<0.05). The acceptance rate of functional rehabilitation of limbs on the affected side was 82.35%(14/17)vs 76.47%(13/17), P<0.05. 【Conclusion】 The application of autologous PRP in the treatment of postoperative bone nonunion for long bone shaft fractures during operation and after operation can achieve good clinical treatment.

Chronic wounds are with characteristics of long last time and cannot heal in time, which is a problem in clinic. Wound pH value plays an important role in the process of healing of chronic wounds. In this paper, we review the relative researches on wound pH value and wound microenvironment, summarize the potential relationship between wound pH value and healing of chronic wounds, as well as the method to change pH value of chronic wounds, thereby to provide theoretical basis for the treatment of chronic wounds in clinic.

Objective: To explore the expression levels of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) protein and the change of MMP-9/TIMP-1 ratio in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers during wound healing. Methods: From July 2017 to July 2018, 30 patients with stage Ⅲ pressure ulcers [30 wounds, 16 males and 14 females, aged (65±10) years] and 34 patients with stage Ⅳ pressure ulcers [50 wounds, 17 males and 17 females, aged (65±9) years] admitted to Hebei General Hospital who met the inclusion criteria were enrolled in this prospective cohort study. According to the principle of wound treatment and the characteristics and needs of wound in different periods, individualized intervention measures were formulated for patients and appropriate dressings were selected. At the time of admission and on 7, 14, 21, 28 days of treatment, the healing of pressure ulcer wounds was evaluated by Pressure Ulcer Healing Scale. Afterwards, the wound exudate was collected at each time point to detect the expression levels of MMP-9 and TIMP-1 protein by enzyme-linked immunosorbent assay, and the MMP-9/TIMP-1 ratio was calculated. Data were processed with analysis of variance for repeated measurements of single group and linear trend test. Results: (1) There were significantly statistical differences in wound healing scores of patients with stages Ⅲ and Ⅳ pressure ulcers among the time of admission and on 7, 14, 21, 28 days of treatment within each stage (F=145.382, 153.234, P<0.01), and they all showed a gradually decreasing trend (F=170.466, 284.585, P<0.01). (2) At the time of admission and on 7, 14, 21, 28 days of treatment, the expression levels of MMP-9 protein in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers were (171±104), (138±88), (110±70), (85±55), (62±41) ng/L and (193±107), (173±104), (139±83), (114±70), (89±56) ng/L, respectively. There were significantly statistical differences within each stage (F=58.007, 111.680, P<0.01), and they all showed a gradually decreasing trend (F=62.901, 134.628, P<0.01). At the time of admission and on 7, 14, 21, 28 days of treatment, the expression levels of TIMP-1 protein in wound exudates of patients with stages Ⅲ and Ⅳ pressure ulcers were (6.2±3.9), (5.6±3.4), (5.1±3.1), (4.4±2.5), (3.8±2.3) ng/L and (4.8±2.5), (4.7±2.6), (4.4±2.6), (4.6±2.7), (4.1±2.4) ng/L, respectively. There were significantly statistical differences within each stage (F=25.479, 7.778, P<0.01), and there was a gradually decreasing trend in stage Ⅲ (F=62.901, P<0.01) and a decreasing trend in stage Ⅳ (F=134.628, P<0.01). At the time of admission, the expression levels of MMP-9 and TIMP-1 in wound exudates of patients with stage Ⅲ pressure ulcers were similar to those of patients with stage Ⅳ pressure ulcers (t=-1.03, 1.47, P>0.05). (3) At the time of admission and on 7, 14, 21, 28 days of treatment, the MMP-9/TIMP-1 ratios in the wound exudates of patients with pressure ulcers of stages Ⅲ and Ⅳ were 30±13, 25±9, 22±9, 20±8, 17±6 and 43±19, 37±13, 32±10, 26±9, 22±9, respectively. There were significantly statistical differences within each stage (F=37.173, 97.191, P<0.01), and they all showed a gradually decreasing trend (F=54.183, 130.088, P<0.01). At the time of admission, the MMP-9/TIMP-1 ratio in wound exudates of patients with stage Ⅳ pressure ulcers was significantly higher than that of patients with stage Ⅲ pressure ulcers (t=-3.42, P<0.01). Conclusions During the wound healing process of patients with stages Ⅲ and Ⅳ pressure ulcers, the expression levels of MMP-9 and TIMP-1 protein and the MMP-9/TIMP-1 ratio in wound exudates show a decreasing trend. The stage of wound healing can be predicted according to the expression level of MMP-9 protein and the MMP-9/TIMP-1 ratio.

Objective To investigate the diagnostic performance of stress cardiac magnetic resonance(CMR) for evaluating low-risk patients with suspected acute coronary syndrome(ACS).Methods Twenty-two patients with low risk of suspected ACS were prospectively and consecutively enrolled in this study.Diagnostic performance of stress CMR was compared with single-photon emission computed tomography(SPECT) for diagnosis of myocardial ischemia with coronary angiography (CAG) as the reference method.Results On the patient-based level analysis,the diagnostic performance of CMR for detection of ACS was sensitivity 93% and specificity 75%.The corresponding value of SPECT was 79%,63%.The area under the ROC (AUC) of CMR was 0.897, which was slightly superior to that of SPECT at 0.723 (P=0.19).On the per-vessel assessment, the diagnostic value of CMR was sensitivity 89%,specificity 87%, while the corresponding value of SPECT was 68%,83%.The AUC of CMR was 0.923,which was significantly higher than that of SPECT at 0.774 (P<0.05).Furthermore, the AUC of CMR was significantly superior to that of SPECT with AUC being 0.900 and 0.553 in the left anterior descending (LAD) vessels (P=0.009 6).Conclusion Stress perfusion CMR has excellent diagnostic performance in low risk ACS patients.Compared with SPECT,stress perfusion CMR performed better in the low-risk ACS populations.

Objective To assess the clinical value of systemic vascular resistance index (SVRI) combined with serum procalcitonin (PCT) and sequential organ failure assessment (SOFA) score in the early diagnosis of sepsis. Methods A retrospective study was conducted. The data of critical patients admitted to Department of Critical Care Medicine of the Third People's Hospital of Hechi from November 2013 to April 2016 were enrolled. The clinical data were recorded as follows: gender, age, infection site, SOFA score, serum PCT level (enzyme linked fluorescence analysis) within 1 hour after intensive care unit (ICU) admission, hemodynamics parameters, including mean arterial pressure (MAP), central venous pressure (CVP), cardiac index (CI), SVRI, global end diastolic volume index (GEDVI), extravascular lung water index (EVLWI), which were monitored by pulse indicator continuous cardiac output (PiCCO) after ICU admission. The patients were divided into sepsis and non-sepsis groups according to the diagnostic criteria of sepsis. Septic patients were divided into low SVRI group, normal SVRI group, and high SVRI group according to SVRI normal value (170-240 kPa·s·L-1·m-2), and the differences in parameters among the three groups were compared. The correlations between SVRI and various parameters were analyzed by using Pearson correlation analysis. The receiver operating characteristic curve (ROC) was plotted to evaluate the diagnostic efficiency of each parameter. Results Totally 103 critical patients were enrolled, 55 in sepsis group, and 48 in non-sepsis group. Compared with non-sepsis group, SVRI in septic group was significantly lowered (kPa·s·L-1·m-2: 146.56±45.17 vs. 188.04±56.27), and serum PCT was significantly increased (μg/L: 10.43±6.17比0.32±0.11) with statistically significant differences (both P < 0.05). In 55 sepsis patients, there were 21 in low SVRI group, 19 in normal SVRI group, and 15 in high SVRI group. There were no statistically significant differences in gender, age and infection site among the three groups, indicating that the baseline data among all groups was balanced with comparability. SOFA score, PCT, and CI in the low SVRI group were significantly higher than those of normal SVRI and high SVRI groups [SOFA: 10.57±2.89 vs. 5.73±2.28, 5.73±2.15, PCT (μg/L): 24.15±12.43 vs. 7.18±5.05, 7.39±4.38, CI (mL·s-1·m-2): 71.01±9.67 vs. 62.01±8.34, 62.51±8.67, all P < 0.05], but no significant difference was found between the normal SVRI group and high SVRI group. There was no statistically significant difference in MAP, CVP, EVLWI, and GEDVI among the three groups. It was shown by Pearson correlation analysis that SVRI was negatively correlated with PCT, SOFA score, and CI (r value was -0.622, -0.598, -0.398, all P = 0.000). It was shown by ROC curve that area under ROC curve (AUC) of PCT combined with SVRI for diagnosis of sepsis was higher than that of PCT or SVRI alone (0.943 vs. 0.911, 0.884). When the cut-off value of PCT was 3.79 μg/L, and cut-off value of SVRI was 156.81 kPa·s·L-1·m-2, the sensitivity and specificity were 94.6% and 92.3% respectively. Conclusions For sepsis patients, SVRI is related to PCT and SOFA score. Combined monitoring of PCT, SVRI, SOFA score can accurately reflect the severity of sepsis patients, guide diagnosis and treatment, and estimate prognosis. The efficacy of PCT combined with SVRI in the early diagnosis of sepsis is better than that of the two alone.

Objective To determine the optimum dose of Oxycodone for anesthesia induction in patients undergoing laparoscopic cholecystectomy. Methods Ninety patients, ASA Ⅰ or Ⅱ , scheduled for elective LC, were randomly divided into 3 groups using random number table (O 1~O 3 groups, n = 30 each). Anesthesia was induced with iv Propofol 1.00~2.00 mg/kg, Oxycodone 0.20 mg/kg, 0.3 mg/kg and 0.4 mg/kg (O 1~O 3 groups, respectively), and Vecuronium 0.10 mg/kg. Before anesthesia induction ( T0 ), 1 min after Laryngeal Mask intubating ( T1 ), the instant of pneumoperitoneum ( T2 ), separation of the gallbladder ( T3 ), wake up immediately ( T4 ), leaving the recovery room ( T5 ), the heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded. At T4, leaving the recovery room ( T5 ), 4 hours after the operation ( T6 ), 8 hours after operation (T7), the numeric pain rating scale (NRS) were recorded. The overall amount of remifentanil and Oxycodone were record. The wake up time, additional analgetic cases and the adverse reactions were recorded. Results The average HR, SBP and DBP fluctuations in the O 2 and O 3 groups were not more than 20.00% of the basal values. There was no significant difference in wake up time between the three groups. There were 22 cases of patients, the NRS> 4, in O1 group requires additional analgesics after they wake up, more than O 2 and O 3 group (7, 3 respectively, P < 0.05). The overall Oxycodone consumption of the three groups were O1: (18.93 ± 4.34) mg (0.90~2.60 mg),O2: (25.50 ± 4.49) mg (1.40~3.00 mg), O3: (26.10 ± 4.55) mg (1.80~3.40 mg) (F = 23.79, P = 0.000). There was no significant difference in adverse reactions between the three groups, but one patient had respiratory depression in O3 group. Conclusion The optimum dose of Oxycodone for anesthesia inducing in laparoscopic cholecystectomy were 0.30 mg/kg.

Objective To investigate the effect of hypothermia on the expression Toll-like receptor 2 (TLR2),myeloid differentiation factor 88(MyD88),nuclear factor-κBp65(NF-κBp65),plasminogen activator inhibitor-1(PAI-1)in the TLR2/MyD88 pathway in rats with acute lung injury(ALI)induced by lipopolysaccharide (LPS)inhalation. Methods Ninety male Sprague-Dawley(SD)rats were randomly divided into control group (n=18),hypothermia group(n=24),temperature controlled group(n=24),and temperature-uncontrolled group(n=24). The ALI model was reproduced by 0.5 mL/kg LPS intratracheal instillation,while only normal saline was instilled intratracheally for control group. Arterial blood was collected and physical cooling was started 1 hour after instillation. The body temperature was lowered to 32-34 ℃in hypothermia group and 36-37 ℃in temperature controlled group,and no intervention was used for temperature-uncontrolled group and control group. The arterial blood gas was determined in all the groups before and 1 hour after instillation of saline or LPS and 1,6, 12 hours after intervention. Rats were sacrificed respectively at 1,6 and 12 hours after temperature control therapy, the morphological changes in lung tissue were observed under light microscope. The protein expression of PAI-1 in bronchoalveolar lavage fluid(BALF)was determined by enzyme linked immunosorbent assay(ELISA). TLR2 mRNA and MyD88 mRNA transcriptional level were determined by reverse transcription-polymeras chain reaction (RT-PCR). NF-κBp65 protein level was determined by Western Blot. Results After instillation of LPS,the oxygenation index(PaO2/FiO2)of each group was decreased obviously,the damage of lung tissues was aggravating,the lung injury score was increased significantly,PAI-1 protein in BALF and the expressions of TLR2 mRNA,MyD88 mRNA, NF-κBp65 protein in lung tissues were increased obviously. Each index was improved by therapeutic Hypothermia, the effect of which was best in using a cooling period in the 1-6 hours,while might be benefit at 6-12 hours. Compared with temperature controlled group,PaO2/FiO2(mmHg,1 mmHg=0.133 kPa)at 1 hour and 6 hours of hypothermia group was improved(1 hour:402.49±38.61 vs. 324.36±28.93,6 hours:349.72±98.20 vs. 284.35±13.68, both P<0.01),the lung injury score at 1,6 and 12 hours were significantly decreased(1 hour:6.04±0.74 vs. 7.96±0.65,6 hours:9.09±0.80 vs. 13.13±1.02,12 hours:10.79±1.42 vs. 13.42±0.68,all P<0.01),the PAI-1 protein(ng/L)in BALF at 1,6 and 12 hours were significantly decreased(1 hour:121.36±4.62 vs. 197.74±9.42, 6 hours:230.53±10.76 vs. 294.06±16.60,12 hours:270.48±13.20 vs. 319.40±10.24,all P<0.01),TLR2 mRNA and MyD88 mRNA expressions(2-ΔΔCt)in the lung tissues at 1,6 and 12 hours were significantly decreased (TLR2 mRNA 1 hour:2.18±0.26 vs. 3.04±0.39,6 hours:4.09±0.29 vs. 4.90±0.35,12 hours:6.02±0.43 vs. 7.10±0.54;MyD88 mRNA 1 hour:2.25±0.41 vs. 3.04±0.30,6 hours:5.67±0.55 vs. 7.01±0.76,12 hours:7.14±0.60 vs. 8.87±0.54,all P<0.01),NF-κBp65 protein expression(A value)at 6 hours and 12 hours was significantly decreased(6 hours:0.31±0.08 vs. 0.53±0.12,12 hours:1.05±0.17 vs. 1.76±0.35,both P<0.01). There was no difference in each index between temperature controlled group and temperature-uncontrolled group. Conclusion Hypothermia can down-regulate the expression of TLR2 mRNA,MyD88 mRNA,NF-κBp65 protein and PAI-1 in the TLR2/MyD88 pathway to protect lung tissue of rats with ALI induced by LPS inhalation from injury.

This article was aimed to study effect of D-ribose on the high-energy phosphate metabolism of skeletal muscle tissues of tired mice. The model was made by burden swimming. And then, the mice were divided into four groups, which were the model group, D-ribose group, caffeine group, and D-ribose with caffeine group). Intragastric administrations of drugs were given to all mice in four groups, three times per day. And all mice continued to swim for three days. The time of swimming was recorded. Gastrocnemius of mice were removed after swimming or 3 days later to measure the concentration of ATP, ADP, AMP and IMP with the HPLC. The results showed that compared with the control group, the time of burden s wimming was significantly prolonged for mice in the D-ribose group and the D-ribose with caffeine group. After three-day recovery, the concentration of ATP, AMP and IMP of gastrocnemius in the D-ribose group and the D-ribose with caffeine group mice was significantly increased. There was no significant difference in the caffeine group mice. It was concluded that D-ribose is involved in the high-energy phosphate metabolism of skeletal muscle tissues of tired mice . D-ribose promotes the recovery of ATP concentration in the gastrocnemius of tired mice, and prolongs the time of burden swimming. Therefore, it has a certain anti-fatigue effect .