Objective:pH low insertion peptide (pHLIP)-variant 7 (var7)-fluorescein isothiocyanate (FITC) was used to explore an accurate imaging tool that targeted burn wounds to better perform burn debridement.Methods:Twelve rat models of burn wound were established and pHLIP-var7-FITC with different concentrations (0.5, 1.5 and 2.0 mg/ml) were injected from the rat tail vein for in vivo fluorescence imaging. By determining the concentration of fluorescent conjugates to the burn wound, the scope of wound injury necrosis was judged by combining pathological sections, and its residue and toxicity in important organs such as heart, liver, kidneys, and brain were detected. The Kruskal-Wallis rank sum test, Bonferroni correction method and one-way analysis of variance were used for data analysis. Results:Within 24 h, the fluorescence photons per unit area of the burn wound in the group of 0.5 mg/ml, 1.5 mg/ml and 2.0 mg/ml were 1.49(1.31, 1.65), 2.46(1.88, 2.68), 2.77 (1.94, 3.10)×10 7 p·s -1·cm -2·Sr -1, with significant differences in the overall distribution of fluorescence photons ( H=73.55, P<0.001). The fluorescence intensity was stronger in the group with higher concentration, but with no significant difference in the number of fluorescence photons between the group of 1.5 mg/ml and 2.0 mg/ml ( P=0.263, Bonferroni correction method). At 14 time points (0.5, 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, 4.0, 5.0, 6.0, 7.0, 8.0, 12, 24 h), there was no significant difference in the overall mean of fluorescence photons ( F=1.04, P=0.419), and the tissue with burn necrosis seen in tissue sections was highly consistent with the fluorescence imaging region. There was no obvious fluorescence residue in the heart, liver, kidney and brain sections. Conclusion:In superficial second-degree burn tissue, pHLIP-var7-FITC can accurately target and gather on the burn wound within 24 h, showing a clear boundary between burn tissue and normal tissue, which can assist clinical surgical debridement to determine the extent of injury.

ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg^-1·d^-1）， and indometacin group （10 mg·kg^-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

[摘 要] 目的：探究虎杖苷通过Hippo/Yes相关蛋白（YAP）通路对人甲状腺癌8505C细胞的恶性生物学行为和顺铂（DDP）敏感性的影响。方法：体外培养8505C细胞，构建其DDP耐药细胞8505C/DDP，用CCK-8法检测0、25、50、75、100 nmol/L虎杖苷处理8505C和8505C/DDP细胞的增殖能力，以筛选虎杖苷的最佳作用浓度。将8505C细胞分为对照组、虎杖苷组、空载组、虎杖苷+YAP1过表达组；将8505C/DDP细胞分为对照组、DDP组、DDP+虎杖苷组、DDP+空载组、DDP+虎杖苷+YAP1过表达组。WB法检测各组8505C细胞中Hippo/YAP通路[YAP1、转录辅激活因子（TAZ）]和EMT（E-cadherin、N-cadherin）相关蛋白，8505C/DDP细胞中YAP1、TAZ、耐药相关蛋白[P-糖蛋白（P-gp）、多药耐药相关蛋白1（MRP1）]、凋亡相关蛋白（C-caspase-3、BAX、Bcl-2）的表达。Transwell小室和细胞划痕实验分别检测各组8505C、8505C/DDP细胞的侵袭、迁移能力。结果：虎杖苷可显著抑制8505C细胞的增殖活性（P<0.05）明显抑制8505C细胞中YAP1、TAZ蛋白、N-cadherin的表达（均P<0.05），提升E-caderin蛋白的表达（P<0.05），显著抑制8505C细胞的迁移和侵袭能力（均P<0.05），而8505C/DDP细胞对低浓度的虎杖苷具有耐药性（P<0.05）；过表达YAP1则可逆转虎杖苷对8505C细胞的影响。50 nmol/L虎杖苷明显抑制DDP处理的8505C/DDP细胞中YAP1、TAZ、P-gp、MRP1、Bcl-2的蛋白的表达（均P<0.05），提升cleaved caspase-3、BAX蛋白的表达（均P<0.05）并诱导其细胞凋亡（P<0.05），过表达YAP1则可逆转虎杖苷对8505C/DDP细胞的影响。结论：虎杖苷抑制Hippo/YAP信号通路，从而抑制8505C细胞的恶性生物学行为和增强其对的DDP敏感性。

Rheumatoid arthritis(RA)is a common systemic autoimmune disease.Chronic synovial inflammation,angiogene-sis,pannus formation,joint destruction of cartilage and bone are important pathological characteristics in RA.Semaphorins(Sema)is a kind of secreted and membrane-bound glycoprotein with nerve guiding effect.Recent studies have shown that Sema family members play an important role in the various pathological stages of RA.Therefore,this paper reviews and discusses the latest research progress on the involvement of Sema family members in different pathological links of RA,which can help to find new feasible targets for RA and provide new research ideas for the pathogenesis of RA.

The number of benign prostatic obstruction (BPO) patients in China is increasing, and patients tend to be younger and younger. The former "gold standard" scheme of transurethral resection of the prostate (TURP) is more suitable for patients with prostate volume ranging from 40 mL to 80 mL, which may lead to excessive resection in patients with small prostate volume and low efficiency in patients with large prostate volume. New minimally invasive techniques have been introduced,including prostate artery embolization, laser surgery (such as holmium, green, diode, and thulium), minimally invasive simple prostatectomy, transperineal laser ablation, prostatic urethral lift,and robot-assisted water jet ablation of the prostate. These methods are alternatives to TURP and increasingly used in the treatment of BPO. This article reviewed the advances in minimally invasive treatment of BPO.

Bladder cancer (BCa) is one of the most common cancers in urology,whose pathogenesis is still unclear. Methyltransferase-like 3(METTL3) is the most important part of N6-methyladenosine methyltransferase complex (m6A MTC),which mediates the methylation of mRNA to regulate the stability and translation process of mRNA. Researches have shown that METTL3 can promote BCa development via AFF4/NF-κB/MYC signaling network,which involves many kinds of signaling molecules. In addition,METTL3 can affect the expressions of AFF4,NF-κB and MYC,so as to affect their downstream signaling pathways and finally promote the malignant progression of tumor.

Objective:To investigate the predictive value of enhanced CT-based radiomics for brain metastasis (BM) and selective use of prophylactic cranial irradiation (PCI) in limited-stage small cell lung cancer (LS-SCLC).Methods:Clinical data of 97 patients diagnosed with LS-SCLC confirmed by pathological and imaging examination in Shanxi Provincial Cancer Hospital from January 2012 to December 2018 were retrospectively analyzed. The least absolute shrinkage and selection operator (LASSO) Cox and Spearman correlation tests were used to select the radiomics features significantly associated with the incidence of BM and calculate the radiomics score. The calibration curve, the area under the receiver operating characteristic (ROC) curve (AUC), 5-fold cross-validation, decision curve analysis (DCA), and integrated Brier score (IBS) were employed to evaluate the predictive power and clinical benefits of the radiomics score. Kaplan-Meier method and log-rank test were adopted to draw survival curves and assess differences between two groups.Results:A total of 1272 radiomics features were extracted from enhanced CT. After the LASSO Cox regression and Spearman correlation tests, 8 radiomics features associated with the incidence of BM were used to calculate the radiomics score. The AUCs of radiomics scores to predict 1-year and 2-year BM were 0.845 (95% CI=0.746-0.943) and 0.878 (95% CI=0.774-0.983), respectively. The 5-fold cross validation, calibration curve, DCA and IBS also demonstrated that the radiomics model yielded good predictive performance and net clinical benefit. Patients were divided into the high-risk and low-risk cohorts based on the radiomics score. For patients at high risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 18.2% in the PCI group, and 61.8% and 75.4% in the non-PCI group, respectively ( P<0.001). In the PCI group, the 1-year and 2-year overall survival rates were 92.9% and 78.6%, and 85.3% and 36.8% in the non-PCI group, respectively ( P=0.023). For patients at low risk, the 1-year and 2-year cumulative incidence rates of BM were 0% and 0% in the PCI group, and 10.0% and 20.2% in the non-PCI group, respectively ( P=0.062). In the PCI group, the 1-year and 2-year overall survival rates were 100% and 77.0%, and 96.7% and 79.3% in the non-PCI group, respectively ( P=0.670). Conclusion:The radiomics model based on enhanced CT images yields excellent performance for predicting BM and individualized PCI.

Objective:To investigate the radiation dose and fractionation regimens for limited stage small cell lung cancer (LS-SCLC) in Chinese radiation oncologists.Methods:Over 500 radiation oncologists were surveyed through questionnaire for radiation dose and fractionation regimens for LS-SCLC and 216 valid samples were collected for further analysis. All data were collected by online questionnaire designed by WJX software. Data collection and statistical analysis were performed by SPSS 25.0 statistical software. The differences in categorical variables among different groups were analyzed by Chi-square test and Fisher's exact test. Results:Among 216 participants, 94.9% preferred early concurrent chemoradiotherapy, 69.4% recommended conventional fractionation, 70.8% preferred a total dose of 60 Gy when delivering conventional radiotherapy and 78.7% recommended 45 Gy when administering hyperfractionated radiotherapy.Conclusions:Despite differences in LS-SCLC treatment plans, most of Chinese radiation oncologists prefer to choose 60 Gy conventional fractionated radiotherapy as the main treatment strategy for LS-SCLC patients. Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN) and Chinese Medical Association guidelines or expert consensus play a critical role in guiding treatment decision-making.

Objective:To investigate the value of derived neutrophil-to-lymphocyte ratio (dNLR) in predicting the prognosis of extensive-stage small cell lung cancer (ES-SCLC) patients treated with the first-line atezolizumab immunotherapy and chemotherapy.Methods:From the Project Data Sphere platform, the clinical data and laboratory test data of 53 ES-SCLC patients who received the first-line atezolizumab immunotherapy and chemotherapy in the global multicenter phase Ⅱ prospective study NCT03041311 from February 2017 to February 2022 were collected. The Contal-O'Quigley method was used to calculate the optimal cut-off value of baseline dNLR for determining the overall survival (OS) of patients. The dNLR higher than or equal to the optimal cut-off value was defined as high dNLR, and less than the optimal cut-off value was defined as low dNLR. According to optimal cut-off value, the dNLR levels at baseline and after 4 cycles of chemotherapy were determined, and dynamic dNLR grouping was performed (low risk: low dNLR at baseline and after 4 cycles of chemotherapy; intermediate risk: high dNLR at baseline or after 4 cycles of chemotherapy; high risk: high dNLR at baseline and after 4 cycles of chemotherapy). The differences in clinicopathological features between the baseline high dNLR group and low dNLR group were analyzed. Kaplan-Meier method was used to draw the OS and progression-free survival (PFS) curves, and log-rank test was used to compare the differences between the two groups. Univariate Cox proportional hazards model was used to analyze the influencing factors of OS and PFS. The time-dependent receiver operating characteristic (ROC) curve was used to evaluate the predictive value of baseline dNLR grouping and dynamic dNLR grouping for 1-year OS rate in ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.Results:Among the 53 patients, 34 (64.20%) were male and 19 (35.80%) were female; 27 (50.90%) were < 65 years old and 26 (49.10%) were ≥65 years old. The optimal cut-off value of baseline dNLR for determining the OS was 1.79. There were 17 cases in low dNLR group and 36 cases in high dNLR group at baseline. The proportion of patients with elevated serum lactate dehydrogenase (LDH) in the baseline high dNLR group was higher than that in the baseline low dNLR group [58.33% (21/36) vs. 17.65% (3/17), χ2 = 7.72, P = 0.005]. The 1-year OS rates of the baseline high and low dNLR groups were 44.0% and 81.9%, and the 1-year PFS rates were 2.5% and 17.6%. The differences in OS and PFS between the two groups were statistically significant (both P < 0.05). There were 38 patients with complete dynamic dNLR data, including 9 cases of low-risk, 19 cases of medium-risk and 10 cases of high-risk, and the 1-year OS rates of the three groups were 90.0%, 67.5% and 33.3%, the difference in OS between the three groups was statistically significant ( P = 0.011). Univariate Cox regression analysis showed that baseline dNLR (low dNLR vs. high dNLR) was the influencing factor for OS of patients ( HR = 0.163, 95% CI 0.057-0.469, P = 0.001) and PFS ( HR = 0.505, 95% CI 0.268-0.952, P = 0.035). Time-dependent ROC curve analysis showed that the area under the curve (AUC) of baseline dNLR grouping and dynamic dNLR grouping for predicting 1-year OS rate of ES-SCLC patients receiving the first-line atezolizumab combined with chemotherapy was 0.674 (95% CI 0.575-0.887) and 0.731 (95% CI 0.529-0.765). Conclusions:Baseline and dynamic dNLR grouping may be effective markers for predicting the prognosis of ES-SCLC patients receiving the first-line atezolizumab immunotherapy and chemotherapy.

Objective:To investigate the factors for and prevention of muscular calf vein thrombosis (MCVT) after unilateral total knee arthroplasty (TKA).Methods:Between January 2018 and October 2020, 551 patients were admitted to Department of Orthopedics, The First Affiliated Hospital to Zhengzhou University for unilateral TKA. They were 187 males and 364 females, aged from 32 to 90 years (average, 64.6 years) and with 234 left and 317 right knees affected. They were assigned into a MCVT group ( n=77) and a non-MCVT group ( n=474) according to whether or not MCVT had happened at 7 days after operation. Recorded were the patients’ baseline information, tourniquet time, intraoperative blood loss, postoperative prothrombin time (PT), postoperative thrombin time (TT), postoperative fibrinogen (FIB), D-dimer, platelet count (PLT), postoperative bed time, knee society score (KSS), erythrocyte sedimentation rate (ESR) fall time, and C-reactive protein (CRP) fall time so as to analyze the risk factors for MCVT. Results:There were significant differences between the 2 groups in age [(66.8±7.0) versus (64.2±9.6) years], body mass index (BMI) [(28.7±2.2) versus (25.0±2.4) kg/m 2], smoking (20/57 versus 41/433), diabetes (56/21 versus 172/302), primary hypertension (45/32 versus 174/300), coronary heart disease (50/27 versus204/270), hyperlipidemia (33/44 versus 149/325), varicosity (50/27 versus 166/308), tourniquet time [(97.9±22.6) versus (83.1±10.6) min], intraoperative blood loss [(73.2±40.6) versus (62.4±11.5) mL], postoperative PT [(10.7±0.8) versus (11.9±1.0) s], TT [(15.2±1.3) versus (17.2±2.4) s], FIB [(3.7±0.8) versus (3.2±0.5) g/L], D-dimer [(1.1±1.0) versus (0.8±0.3) μg/L], PLT [(233.4±68.5) versus (178.5±27.8) 10 9/L], postoperative bed time [(17.3±2.6) versus (14.6±3.8) h], KSS [(3.32±0.7) versus (3.61±0.56) points], ESR fall time [(2.90±0.74) versus (1.55±0.64) d] and CRP fall time [(2.90±0.74) versus (1.55±0.64) d] (all P<0.05). Multivariate logistic regression analysis showed that old age (95% CI: 0.890 to 1.112, P=0.034), high BMI (95% CI: 1.012 to 1.214, P=0.046), diabetes (95% CI: 1.002 to 2.590, P=0.020), D-dimer (95% CI: 1.239 to 10.292, P=0.001) and postoperative PLT (95% CI: 1.012 to 1.112, P=0.014) were independent risk factors for MCVT. Reduced postoperative bed time (95% CI: 1.009 to 1.469, P=0.040) was a protective factor. Conclusions:As old age, high BMI, diabetes, and high postoperative levels of D-dimer and PLT may be independent risk factors for MCVT, patients with such characteristics should be alert to MCVT. Early ambulation should be encouraged in patients after unilateral TKA to reduce postoperative bed time for prevention of the disease.