1.Expert consensus on neoadjuvant PD-1 inhibitors for locally advanced oral squamous cell carcinoma (2026)
LI Jinsong ; LIAO Guiqing ; LI Longjiang ; ZHANG Chenping ; SHANG Chenping ; ZHANG Jie ; ZHONG Laiping ; LIU Bing ; CHEN Gang ; WEI Jianhua ; JI Tong ; LI Chunjie ; LIN Lisong ; REN Guoxin ; LI Yi ; SHANG Wei ; HAN Bing ; JIANG Canhua ; ZHANG Sheng ; SONG Ming ; LIU Xuekui ; WANG Anxun ; LIU Shuguang ; CHEN Zhanhong ; WANG Youyuan ; LIN Zhaoyu ; LI Haigang ; DUAN Xiaohui ; YE Ling ; ZHENG Jun ; WANG Jun ; LV Xiaozhi ; ZHU Lijun ; CAO Haotian
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(2):105-118
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.
2.Study on the mechanism of different concentrations of simvastatin on regeneration of sciatic nerve injury in rats
Yun-hu LI ; Jun-wei CAO ; Chen LI ; Jing-yu ZHANG ; Ai-she DUN ; Hong-bin WANG
Journal of Regional Anatomy and Operative Surgery 2025;34(9):772-775
Objective To explore the effects of different concentrations of simvastatin on nerve regeneration after sciatic nerve injury.Methods Rats were randomly divided into the normal group,the control group,the low-dose group and the high-dose group,with 3 rats in each group.Except for the normal group,adult rat sciatic nerve crush injury models were established in the other groups.Rats in the normal group and the control group were orally administered with water,while those in the low-dose group and high-dose group were orally administered with 98%simvastatin at dosages of 4 mg/mL and 40 mg/mL,respectively.The sciatic nerve regeneration in rats was evaluated by sciatic function index(SFI),HE staining,luxol fast blue(LFB)staining and immunofluorescence staining,etc.Results The SFI of rats in the high-dose group 7 days and 14 days after surgery were higher than those in the control group(P<0.05);there was no significant difference in SFI of rats between the low-dose group and the control group 7 days and 14 days after surgery(P>0.05).HE staining and LFB staining results showed that compared with the control group,the number of neurons of rats in the high-dose group increased,the nerve fibers and myelin were clearer and denser,and the nerve function was significantly restored;while no significant improvement was observed in the sciatic nerve of rats in the low-dose group.The immunofluorescence staining results showed that compared with the control group,the immunofluorescence intensity in the high-dose group increased,while that in the low-dose group decreased,the differences were statistically significant(P<0.05).Conclusion High-dose simvastatin can promote peripheral nerve regeneration by regulating the expression of M2 macrophages.
3.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
4.Advances in the use of human respiratory stem cells in the treatment of respiratory tract infections
Xuan LIU ; Wenyan TIAN ; Ze CHEN ; Yingli QU ; Jin CAO ; Chenxi ZHANG ; Qi WEN ; Qin LUO ; Qiangqiang SHI ; Lifeng ZHANG ; Guoyong MEI ; Haijun DU ; Zhiqiang XIA ; Jun HAN
Chinese Journal of Experimental and Clinical Virology 2025;39(1):128-132
Human Respiratory Stem Cells (RSCs) play a crucial role in the maintenance, repair and regeneration of the respiratory system. As a novel therapeutic method, stem cell therapy is a popular research direction in the medical field. And with the in-depth research on the mechanism of pneumonia caused by respiratory infections in recent years, the use of RSCs to explore pneumonia caused by respiratory infections and its therapeutic strategies has become a hot topic. In this paper, we firstly outlined the types of RSCs, summarized the mechanism of pneumonia caused by respiratory tract infections, discussed the advantages of RSCs application and the progress of culture differentiation, and elaborated the therapeutic exploration of RSCs in pneumonia caused by respiratory tract infections.
5.Effects of proton FLASH irradiation and conventional irradiation on the cell cycle and death of renal cancer cells
Jun ZHANG ; Siqian ZHANG ; Qiaojuan WANG ; Li SUI ; Yongsheng ZHANG ; Zhifei CAO
Chinese Journal of Radiological Medicine and Protection 2025;45(11):1100-1106
Objective:To explore the effects of proton FLASH irradiation (FLASH-IR) and conventional irradiation (CONV-IR) on the cell cycle, apoptosis, and pyroptosis of renal cancer cells.Methods:Renal cancer cells (769-P) were irradiated with 8 Gy of protons at a dose rate of 40 Gy/s for FLASH-IR and 0.4 Gy/s for CONV-IR, Ctrl group was treated without irradiation. Cells were collected 24 h after irradiation. The changes in the cell cycle were measured using flow cytometry. The expression of genes and proteins related to the cell cycle, apoptosis, and pyroptosis signaling pathways in renal cancer cells was measured using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot.Results:Proton FLASH-IR increased the proportion of renal cancer cells in the G 0/G 1 phase [FLASH-IR group vs. Ctrl group, (67.01±0.44)% vs. (38.68±0.63)%, t = -63.99, P<0.05], while CONV-IR increased the proportion of renal cancer cells in the G 2/M phase [CONV-IR group vs. Ctrl group, (56.65±1.52)% vs. (23.67±0.51)%, t = -29.17, P<0.05]. Both proton FLASH-IR and CONV-IR caused apoptosis of renal cancer cells ( tFLASH= -16.24 to -5.01, P <0.05; tCONV=-20.08 to 6.11, P < 0.05) and CONV-IR activated the P53/P21 pathway ( t = -16.86 to -9.74, P < 0.05). Both proton FLASH-IR and CONV-IR induced pyroptosis of renal cancer cells ( tFLASH= -23.36 to 20.18, P <0.05; tCONV=-41.62 to 13.95, P <0.05), and the former exhibited a greater effect (FLASH-IR group vs. CONV-IR group, 0.96±0.01 vs. 0.68±0.44, t = -10.46, P <0.05). Conclusions:Both proton FLASH-IR and CONV-IR bring about changes in the cell cycle of renal cancer, promoting apoptosis and pyroptosis. However, there are differences between the two mechanisms that require further exploration. Proton FLASH-IR holds promise for the treatment of renal cancer.
6.Construction and application of a nursing consultation information system based on information interaction needs
Chan HUANG ; Yanyu CHI ; Yudi MIN ; Peiye CAO ; Jun LIU ; Rongxin ZHENG ; Haiyan ZHANG
Chinese Journal of Nursing 2025;60(6):645-651
Objective To construct a nursing consultation information system based on consultation process and information interaction needs and explore its application effect.Methods The nursing consultation process and information interaction needs were analyzed;the information process,content modules and information interaction interface were designed;the structured records for nursing consultation were developed.The system was officially applied in January 2024.The application effect was evaluated by comparing the completion time of nursing consultations,nursing consultation record quality score,nursing consultation evaluation completion rate,and satisfaction rate before(August 2023 to October 2023)and after(January 2024 to March 2024)the application of the information system.Results After the application of the nursing consultation information system,the implementation rate of nursing consultation for inpatients increased from 1.27% before the application of the system to 1.47%(P=0.019).The completion time of nursing consultation in the whole hospital reduced from 351(225,421)minutes before the application of the system to 310(156,402)minutes(P<0.001),and there was a statistically significant difference in the completion time of nursing consultation among the 3 specialties of intravenous therapy,blood purification,and diabetes nursing(P<0.05).The quality score of nursing consultation records increased from 90.5(82.0,100)points to 95.5(92.0,100)points(P<0.001).The completion rate of nursing consultation evaluation was higher than those before the system application,with statistical significance(21.6% vs 78.4%,P<0.001).Conclusion Nursing consultation information system based on information interaction needs can improve the implementation of nursing consultation for inpatients,shorten the completion time of nursing consultations,improve the writing quality of nursing consultation records and the completion rate of nursing consultation evaluation,and it succeeded in real-time quality monitoring.
7.Correlation between the hemoglobin glycation index and carotid intraplaque neovascularization
Hao ZHANG ; Shugang CAO ; Jun HE ; Mingwu XIA
Chinese Journal of Cerebrovascular Diseases 2025;22(5):310-316,348
Objective To investigate the correlation between the hemoglobin glycation index(HGI)and the severity of intraplaque neovascularization(IPN)in patients with mild-to-moderate carotid artery stenosis.Methods This study retrospectively and consecutively enrolled patients with mild-to-moderate carotid artery stenosis(<70%narrowing)hospitalized in the Department of Neurology at the Hefei Second People's Hospital between June,2020 and June,2024.Demographic data(age,gender),personal history(smoking,drinking),cerebrovascular risk factors(hypertension,diabetes,hyperlipidemia),body mass index,and laboratory indicators from fasting venous blood collected on the second morning of hospital admission(neutrophils,lymphocytes,neutrophil-to-lymphocyte ratio,platelet count,total cholesterol,triglycerides,high-density lipoprotein cholesterol,low-density lipoprotein cholesterol(LDL-C),homocysteine,blood glucose,and glycated hemoglobin[HbA1c])were collected and compared.A univariate linear regression analysis was performed to assess the relationship between fasting blood glucose and HbA1c levels measured on the second day after admission,yielding the prediction formula:predicted HbA1c(%)=0.571×fasting blood glucose(mmol/L)+3.125.Subsequently,HGI was calculated through:HGI=actual HbA1c-predicted HbA1c.Carotid ultrasound was used to measure patients'carotid intima-media thickness,and,plaque location,thickness(maximum plaque diameter),length,echogenicity,and resistance index.For patients with multiple plaques,the thickest plaque was selected as the target plaque.Using the AngioPLUS mode of carotid ultrasound,dynamically observe for presence of IPN at the filling defect of the carotid artery plaque.The IPN condition of the target plaque was then assessed,including the number,location,morphology(e.g.,punctate,short linear,etc.),and spectral Doppler characteristics of the new blood vessels.The IPN signals were counted and scored according to the following criteria:absence of high-echogenicity blood flow signals in the target carotid artery plaque indicating no neovascularization,was scored as 0 point;the presence of fewer than 4 punctate or short linear hyperechoic blood flow signals within the target plaque was scored as 1 point;the presence of diffusely distributed(≥4)short linear or strip-like hyperechoic blood flow signals within the plaque was scored as 2 points.A higher IPN score indicates a more severe degree of IPN.Patients with an IPN score of 0-1 were categorized as the low IPN score group,while those with an IPN score of 2 were classified as the high IPN score group.Indicators with statistically significant differences between the two groups in the univariate analysis and exhibited no multicollinearity were included in the multivariate binary Logistic regression model to analyze the relationship between HGI and the severity of carotid IPN.Results A total of 387 patients(222 males and 165 females,with a mean age of[70±10]years)with mild-to-moderate carotid artery stenosis were included in this study.Among the 387 patients enrolled,97 were in the low IPN score group,while 290 were in the high IPN score group.(1)The high IPN score group exhibited significantly higher average age([71±10]years vs.[67±10]years),higher prevalence of hypertension(79.7%[231/290]vs.67.0%[65/97]),higher prevalence of diabetes(37.6%[109/290]vs.14.4%[14/97]),greater plaque thickness(2.40[2.00,3.10]mm vs.2.30[1.80,2.70]mm),higher HbA1c levels(6.25%[5.70%,7.20%]vs.5.80%[5.50%,6.40%]),and higher HGI values(-0.05%[-0.39%,0.46%]vs.-0.29%[-0.56%,-0.10%])in comparison to the low IPN score group(all P<0.05).Additionally,the high IPN score group had significantly lower lymphocyte ratios([27.75±9.19]%vs.[30.17±9.04]%)and lower LDL-C levels([2.19±0.81]mmol/L vs.[2.43±0.91]mmol/L;both P<0.05).(2)The results of multivariate Logistic regression analysis indicated that age(OR,1.031,95%CI 1.004-1.060,P=0.027),HGI(OR,1.782,95%CI 1.066-2.979,P=0.028),and plaque thickness(OR,1.750,95%CI 1.229-2.490,P=0.002)were independent influencing factors associated with the severity of IPN in the mild-to-moderate carotid artery stenosis.Conclusions High HGI may serve as an independent risk factor for the severe IPN in patients with mild-to-moderate carotid artery stenosis.However,the findings of this study require further validation through multi-center,large-scale,prospective clinical trials.
8.Clinical investigation of minimally invasive double anchoring combined with percutaneous vertebral augmentation in the treatment of Kümmell disease
Qing FENG ; Jun MIAO ; Shenglin CAO ; Zepei ZHANG ; Yingbo LIU ; Wang REN ; Hongwei FENG ; Bin DONG ; Chao LI ; Ning JI ; Bingyao ZHANG ; Lijun AN
Chinese Journal of Orthopaedics 2025;45(7):412-419
Objective:To investigate the clinical efficacy of minimally invasive double anchoring combined with percutaneous kyphoplasty (PKP) for Kümmell disease.Methods:The clinical data of 24 patients with Kümmell disease who were treated with minimally invasive double anchoring combined with PKP in Cangzhou People's Hospital from October 2022 to March 2024 were retrospectively analyzed. Among them, there were 2 T 10 vertebrae, 5 T 11 vertebrae, 7 T 12 vertebrae, 6 L 1 vertebrae, and 4 L 2 vertebrae. There were 6 males and 18 females. The average age was 72.05±4.52 years (range, 66-80 years). The bone mineral density T value was -3.41±0.77 (range, -2.5-4.5). The stages of Li's Kümmell disease included 13 cases of stage II and 11 cases of stage III. The operation time, intraoperative blood loss, and volume of bone cement injected were recorded. The vertebral index, vertebral angle and Cobb angle of diseased segment were measured before and after operation. The visual analogue scale (VAS) was used to assess the degree of pain, the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) low back pain scale were used to assess spinal function. The Medical Outcome Study short form 36 item health survey (SF-36) was used to assess the general health status of the patients. The postoperative symptom recovery was evaluated by Odom criteria. Results:The mean operative time of the 24 patients was 35.32±6.86 min, the injected volume of bone cement was 4.39±1.72 ml, and the intraoperative blood loss was 16.56±5.21 ml. All patients were followed up for 10 to 14 months, with an average of 11.7 months. Postoperative CT examination showed that the screw positions were satisfactory, and no loosening or displacement of bone cement mass occurred. On the first day after surgery, the vertebral body index, vertebral body angle and Cobb angle of diseased segment were 77.71%±2.75%, 12.40°±1.53° and 25.77°±4.49°, respectively, which represented significant improvements from the preoperative values of 43.09%±5.66%, 22.12°±2.92° and 46.98°±5.68° before surgery ( P<0.05). At the last follow-up, the values were 76.18%±2.32%, 12.41°±2.53°, 26.14°±4.87°, respectively, which were significantly improved compared with those before surgery ( P<0.05), but there was no statistical significance compared with the first day after surgery ( P>0.05). The VAS, ODI and JOA scores on the first day after surgery were 2.11±0.87 points, 22.46±5.49 points and 27.68±2.45 points, respectively, which were significantly improved compared with those before surgery 7.50±0.98 points, 76.25±8.56 points and 14.96±4.91 points ( P<0.05). At the last follow-up, the values were 2.26±0.88, 23.87±3.25 and 26.58±2.77, respectively, which were significantly improved compared with those before surgery ( P<0.05), and there was no statistical significance compared with the first day after surgery ( P>0.05). All 24 patients completed SF-36 scale assessment, and the results showed that there were statistically significant differences in physiological function, physiological role, physical pain, general health status, social function scores and mental health between the patients before surgery and the last follow-up ( P<0.05), while there were no statistically significant differences in vitality and emotional function ( P>0.05). At the last follow-up, the Odom criteria showed excellent results in 18 cases, good in 4 cases, and fair in 2 cases. Conclusions:The application of minimally invasive double anchoring (single nail fixation) combined with PKP in the treatment of Kümmell disease can effectively prevent the loosening and displacement of bone cement masses, and the fixation effect is satisfactory, which can restore the height of the injured vertebrum, reduce kyphosis and improve spinal function. The clinical symptoms of the patients were significantly improved, and the quality of life was enhanced.
9.Current status and advances in the diagnosis and treatment of inflammatory breast cancer
Wenjing ZENG ; Juan HUANG ; Shouman WANG ; Yangyi LI ; Weizhi XIA ; Yulong ZHANG ; Jun WU ; Taohong SHEN ; Fangli ZHOU ; Ayong CAO
Chinese Journal of General Surgery 2025;34(5):1044-1055
Inflammatory breast cancer(IBC)is a rare but highly aggressive subtype of breast cancer characterized by rapid clinical progression and poor prognosis.Although it accounts for only 2%-4%of all breast cancer cases,it is responsible for 8%-10%of breast cancer-related mortality.The etiology of IBC is multifactorial,involving genetic,hormonal,environmental,and socioeconomic factors.Pathologically,IBC is marked by the presence of dermal lymphatic tumor emboli,and molecular subtypes are predominantly HER2-positive and triple-negative,indicating high tumor invasiveness.Diagnosis relies on characteristic clinical manifestations and histopathological confirmation,while imaging techniques such as MRI and PET/CT play important roles in evaluating disease extent and metastasis.Given that IBC is often diagnosed at a locally advanced or metastatic stage,there is currently no specific treatment protocol.Instead,management generally follows the treatment paradigm of non-IBC,emphasizing systemic therapy within a multidisciplinary framework.HER2-positive IBC benefits from chemotherapy combined with dual-targeted anti-HER2 therapy;triple-negative IBC may respond to immune checkpoint inhibitors;and CDK4/6 inhibitors show potential efficacy in hormone receptor-positive subtypes.Despite advancements,the prognosis remains poor,with a high risk of early recurrence and distant metastasis.Prognostic factors include lymph node involvement,molecular subtype,and response to neoadjuvant therapy.As research into the tumor microenvironment and molecular mechanisms deepens,targeted and individualized therapies hold promise for improving outcomes.This review summarizes the epidemiology,pathology,diagnostic criteria,treatment strategies,and prognostic factors of IBC,aiming to inform clinical practice and future research.
10.Role of spinal SGK-1/Kalirin-7/NR2B signaling pathway in type 2 diabetic neuropathic pain in rats
Jiali CHEN ; Maobiao ZHANG ; Hong CAO ; Jun LI
Chinese Journal of Anesthesiology 2025;45(1):65-70
Objective:To evaluate the role of spinal serum and glucocorticoid-inducible kinase 1(SGK-1)/Kalirin-7/N-methyl-D-aspartate receptor 2B(NR2B) signaling pathway in the type 2 diabetic neuropathic pain(DNP) in rats.Methods:Clean-grade male Sprague-Dawley rats, aged 6 weeks, weighing 120-160 g, were randomized to receive a normal diet(normal control group [group C, n=12]) or a high-fat and high-glucose diet( n=60). Diabetes mellitus was induced by single intraperitoneal injection of streptozotocin 35 mg/kg after 8 weeks of a high-fat and high-glucose diet. The successful DNP model was defined as a decrease in the pain threshold(mechanical paw withdrawal threshold [MWT] and thermal paw withdrawal latency [TWL]) to less than 85% of the baseline value in type 2 diabetic rats. Twelve non-DNP(pain threshold above 85% of the baseline value) rats with type 2 diabetes mellitus were randomly selected and included in non-DNP group(NDNP group). Thirty-six rats with DNP were divided into 3 groups( n=12 each) using a random number table method: DNP group, DNP plus SGK1 inhibitor GSK-650394 group(DNP+ G group), and DNP plus solvent control group(DNP+ SC group). At day 14 after STZ injection, GSK-650394(10 μl) 300 nmol/L was intrathecally injected once a day for 14 consecutive days in DNP+ G group. DNP group did not receive any treatment, and the rats in DNP+ SC group received intrathecal injection of the equal volume of dimethyl sulfoxide. The MWT and TWL were measured after 8 weeks of feeding, at 14 days after STZ injection, and at 3, 7 and 14 days after intrathecal injection(at 17, 21 and 28 days after STZ injection). After 7 days of intrathecal injection, the lumbar enlargement tissues of the spinal cord were collected for determination of the expression of SGK-1, phosphorylated SGK-1(Ser422-SGK1), Kalirin-7, phosphorylated NR2B(Tyr1472-NR2B), and NR2B by Western blot. The ratios of Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B were calculated. Results:Compared with C group, the MWT was significantly decreased and TWL was shortened at 14 days after STZ injection and at the corresponding time points of intrathecal injection, and the ratios of spinal Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B were increased, and the expression of Kalirin-7 was up-regulated in DNP group( P<0.05), and no statistically significant change was found in the aforementioned parameters in NDNP group( P>0.05). Compared with DNP group, the MWT was significantly increased and TWL was prolonged at 3, 7 and 14 days of intrathecal injection, the ratios of Ser422-SGK1 to SGK1 and Tyr1472-NR2B to NR2B in the spinal cord tissue were decreased, Kalirin-7 expression was down-regulated( P<0.05), and no statistically significant differences were found in the aforementioned parameters in DNP+ SC group( P>0.05). Conclusions:The enhanced phosphorylation of SGK-1 in the spinal cord of DNP rats may play an important role in the occurrence and maintenance of DNP probably by activating the Kalirin-7/NR2B signaling pathway.


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