Abstract:Immune checkpoint inhibitors (ICPis) are emerging anti-tumor drugs, with endocrine adverse reactions as its most common adverse drug reactions, and mainly involves multiple endocrine glands, such as glands of thyroid, pituitary, adrenal and pancreas, leading to endocrine dysfunction. If its emergencies can not be correctly identified and prevented in the early stage, it may be life-threatening. Although a number of relevant guidelines/consensuses have been published at home and abroad, there is no consensus on the diagnosis and treatment process of endocrine adverse reactions caused by ICPis in China. In order to standardize and improve the clinical diagnosis and treatment level of relevant departments, we have reviewed and analyzed a number of domestic and international expert consensuses and clinical studies, and formulated this consensus based on integration of the opinions of oncology, endocrinology and nursing experts.

Abstract:The prevalence rate of diabetes is the highest in chronic metabolic diseases of China, the incidence rate of malignant tumors is also increasing year by year, and they are closely related. Systematic and standardized guidance is deficient in the management of tumor associated hyperglycemia. Endocrinology and oncology experts from the Onco-endocrinology Society of Chinese Anti-Cancer Association and Onco-endocrinology Society of Chongqing Integrative Medicine Association have summarized the research progress and evidence-based basis of tumor associated hyperglycemia, and drafted the Guidelines for the Management of Tumor Associated Hyperglycemia (2021 Edition), which provides a systematic and detailed introduction to the conception, clinical diagnosis, treatment and follow-up of tumor associated hyperglycemia. In order to comprehend relevant opinions better, we provide an interpretation in this paper.

Abstract:Objective:　To explore the repairing effect of exosomes derived from human umbilical cord mesenchymal stem cells (HucMSCs) on the skull defect of osteoporosis rats. Methods:　Isolation the exosomes from HucMSCs, the morphology and size of the exosomes were identified by transmission electron microscopy and nanoparticle tracking analysis, and the surface markers were identified by Western blot. Rat bone marrow mesenchymal stem cells (BMSCs) were isolated and their surface markers were identified by flow cytometry. Exosomes (control, 20 μg/mL, 40 μg/mL, 60 μg/mL, 80 μg/mL) were co-cultured with BMSCs, and the effects of different concentra-tions of exosomes on proliferation and early osteogenic differentiation of BMSCs were detected. Osteoporosis model was established by ovariectomy (OVX) in SD rats. Exosomes suspension was injected at the same time as the skull defect model was estab-lished. Eight weeks after operation, the rats were euthanized. micro-CT scanning and bone mass analysis was performed on the tissue of the operation area, and the healing of bone defect was observed under microscope after HE staining, so as to evaluate the repairing potential of exosomes from HucMSCs on the skull defect of osteoporosis rats. Results:　The results of transmission electron microscope and nanoparticle tracking analysis showed that the shape and size of exosomes derived from HucMSCs met the requirements, and the expression of surface protein markers CD63 and CD81 were positive. The surface markers CD29, CD90 and CD45 of rats BMSCs were expressed as 99.86%, 99.50% and 4.12% respectively, which accorded with the characteristics of mesenchymal stem cells. After co-culturing 60 μg/mL exosomes with BMSCs for 5 days, the cell viability was (127.782±7.184) % of the control group (P=0.001), the expression of alkaline phosphatase (ALP) was (2.715±0.095) times of the control group (P=0.003), and the expression of Runx family transcription factor 2 (Runx2) was (2.175±0.731) times of the control group (P=0.140). In the repair of an OVX-induced osteoporosis SD rat skull defect model, micro-CT showed that the exosome group had a significant increase in bone healing compared with the control group. The results of bone mass analysis showed that in the exosome group, the bone volume/tissue volume was (11.000±1.708) % (P=0.008), the trabecular number was (0.742±0.112) mm^-1 (P=0.014), the trabecular thickness was (0.175±0.008) mm (P=0.005), and the trabecular separation was (1.402±0.507) mm (P=0.022). Histological results showed that the new bone had a complete structure, with clear layers, as dense lamellar bone, and uniform bone matrix and bone lacunae. Conclusion:　The exosomes derived from HucMSCs can promote the proliferation and osteogenic differentiation of BMSCs, and have the ability to repair osteoporotic bone defects.

Abstract:Objective:　To investigate the role of "Sirt1-autophagy" on the hypoxia-induced apoptosis in OCCM-30 cementoblasts of mouse. Methods:　OCCM-30 cells were cultured in vitro and were randomly divided into the control group, the hypoxia group, the hy-poxia + resveratrol group, the hypoxia + 3-MA group, the hypoxia + resveratrol + ex527 group and the hypoxia + resveratrol + 3-MA group. Changes of autophagy lysosomes in each group were observed by MDC staining and changes of autophagosome light chain Ⅱ (LC3 Ⅱ) were detected by immunofluorescence assay. The expression of Sirt1, LC3 Ⅱ and p62 proteins was detected by Western blot. Cell apoptosis was detected by flow cytometry. Results of different groups were analyzed by one-way ANOVA and different groups were analyzed by LSD-t. Results:　Compared with the control group, the content of autophagy lysosomes (P=0.000) and the number of autophagosomes (P=0.000) in the hypoxia group were significantly increased, the expression of LC3 Ⅱ (P=0.001) protein was signifi-cantly increased, the expression of p62 protein was significantly decreased (P=0.000), and the apoptosis rate was increased (P=0.000). Compared with the hypoxia group, the number of autophagy lysosomes (P=0.019) and autophagosomes (P=0.000), and the expression of LC3 Ⅱ protein (P=0.000) and Sirt1 protein (P=0.049, P=0.000) in the hypoxia + resveratrol group were significantly increased, the expression of p62 protein (P=0.000) was signifi-cantly decreased, and the apoptosis rate was decreased (P=0.021). Compared with the hypoxia + resveratrol group, the number of autophagy lysosomes (P=0.000) and autophagosomes (P=0.000), and the expression of LC3 Ⅱ (P=0.000) and Sirt1 (P=0.000) in the hypoxia + resveratrol + ex527 group were sig-nificantly decreased, the expression of p62 protein (P=0.000) was significantly increased, and the apoptosis rate was increased (P=0.000). Compared with the hypoxia + resveratrol group, the num-ber of autophagy lysosomes (P=0.000) and autophagosomes (P=0.000), and the expression of LC3 Ⅱ (P=0.000) protein expression in the hypoxia + resveratrol + 3-MA group were significantly decreased, the expression of p62 protein (P=0.000) was increased, the apoptosis rate was increased (P=0.000), and the expression of Sirt1 protein (P=0.146) was decreased, with no statistically significant difference. Conclusion:　Autophagy-related molecules may be downstream acting molecules of Sirt1 in the hypoxic environment and autophagy plays a protective role in hypoxia-induced apoptosis of OCCM-30.

Abstract:Objective:　To explore the potential molecular mechanism of coenzyme Q₁₀ (CoQ₁₀) on the proliferation and migration of colorectal cancer cells. Methods:　SW480 cells and RKO cells were treated with CoQ₁₀ respectively, then cell count and cell scratch experiment were conducted to explore the effect of CoQ₁₀ on the proliferation and migration of colorectal cancer cells. SW480 cells were treated with CoQ₁₀ and then flow cytometry was performed to explore the effect of CoQ₁₀ on cell cycle and apoptosis of colorectal cancer SW480 cells. In order to explore the effect of CoQ₁₀ on gene expression profile of colorectal cancer RKO cell line, RKO cells treated with CoQ₁₀ were analyzed by RNA-seq sequencing, and the results were analyzed by GO and KEGG pathways. Finally, quanti-tative RT-PCR was used to verify the RNA-seq results. Results:　①CoQ₁₀ did not affect the proliferation, cell cycle, apoptosis and mi-gration of colorectal cancer cell SW480, nor did it affect the proliferation of colorectal cancer cell RKO, but it inhibited the migration of RKO. ②The RNA-seq results showed that differentially expressed genes were significantly enriched in cell adhesion molecule sig-naling pathway, extracellular matrix receptor signaling pathway and cholesterol signaling pathway. Quantitative RT-PCR results showed that CoQ₁₀ treatment did significantly up-regulate the expression of PCSK9, HMGCR, HMGCS1 and DHCR7 genes in cholesterol synthesis pathway. These results suggest that CoQ₁₀ may inhibit RKO migration in colorectal cancer cells by regulating the expression of these genes. Conclusion:　CoQ₁₀ has no significant effect on the proliferation of colorectal cancer cells, but may inhibit the migra-tion ability of partial colorectal cancer cells by regulating cholesterol metabolism.

Abstract:Objective:　To investigate the effect of suppressor of cytokine signaling 2 (SOCS2) overexpression on the growth, movement and JAK2/STAT3 pathway of rectal cancer cells. Methods:　HCT8 cells were divided into control group, pcDNA group and pcDNA-SOCS2 group, transfected with pcDNA empty vector or pcDNA-SOCS2 group recombinant expression vector according to different groups. SOCS2 gene expression was detected by RT-PCR, cell proliferation was detected by BrdU staining, flow cytometry was used to detect apoptosis, Transwell method was used to detect cell invasion, and Western blot was used to detect SOCS2, E-cadherin, vimentin, fibronectin protein expression, and phosphorylation of JAK2 and STAT3. In addition, BALB/c nu/nu nude mice were divided into con-trol group and pcDNA-SOCS2 group. HCT8 subcutaneous xenograft model was established, and the weight of xenograft tumor was weighed. The average optical density of Ki-67 and vascular endothelial growth factor (VEGF) was measured by immunohistochemistry, and the Western blot was used to detect the phosphorylation of JAK2 and STAT3 in tumor tissues. Results:　In the ex-vivo experiment, the RT-PCR results showed that compared with the control group (1.00±0.00), the SOCS2 mRNA level (4.70±0.27) of the pcDNA-SOCS2 group was significantly increased (P=0.000). Western blot results showed that the expression of SOCS2 protein in the pcDNA-SOCS2 group (0.130±0.020) was significantly up-regulated (P=0.000) compared with that in the control group (0.010±0.005). The percentage of BrdU positive was signifi-cantly reduced (P=0.000); flow cytometry results showed that the apoptosis rate of HCT8 cells in the pcDNA-SOCS2 group [(35.0±5.0) %] was significantly higher than that in the control group [(6.0±3.4) %, P=0.000]. Transwell analysis results showed that the number of HCT8 cell invasions in the pcDNA-SOCS2 group (89.0±10.0) was significantly lower than that of the control group (87.0±13.0, P=0.000). Western blot results showed that the E-cadherin protein level (0.120±0.030) of HCT8 cells in the pcDNA-SOCS2 group was significantly increased compared to the con-trol group (0.010±0.004, P=0.000), while the Vimentin protein level (0.008±0.004) and Fibronectin protein level (0.010±0.005) were significantly reduced compared to the control group (0.170±0.024, 0.070±0.020), P=0.000, the phosphorylation level of JAK2 and STAT3 decreased (P=0.000). In the in-vivo experiment, the tumor weight in the pcDNA-SOCS2 group (0.14±0.06) was signifi-cantly less than that in the control group (0.45±0.08, P=0.000). The results of immunohistochemistry showed that the average optical density of Ki-67 and VEGF in the pcDNA-SOCS2 group (17.0±6.0, 7.0±6.0) was significantly lower than that in the control group (52.0±9.0, 43.0±9.0, P=0.000), and the phosphorylation levels of JAK2 and STAT3 tumor bodies were significantly down-regulated (P=0.000). Conclusion:　The overexpression of SOCS2 can inhibit the proliferation and exercise ability of rectal cancer HCT8 cells and promote the apoptosis, which is related to JAK2/STAT3 pathway.

Abstract:Objective:　To compare the application value of endorectal ultrasonography (ERUS) with two kinds of probe in preoperative T staging of rectal cancer and the value of the two probes in the staging of rectal cancer at different positions. Methods:　The data of 440 patients with rectal cancer in our hospital from January 2014 to September 2021 were collected (277 cases of straight convex probe and 163 cases of circumferential scanning probe), and 301 patients with preoperative ERUS and postoperative pathological findings were screened out. Then the results of preoperative ultrasound T-staging (uT) and pathological staging (refer to the eighth edition of AJCC) were compared to calculate the sensitivity, specificity and accuracy of preoperative ultrasound staging. Results:　The results of ultrasonography and pathology of 180 cases of rectal cancer (straight convex probe) were compared, and the total accuracy of uT by ERUS was 73%. The accuracy of each stage was T1 97%; T2 91%; T3 79%; T4 79%. The results of ultrasonography and pathology of 121 cases of rectal cancer (circumferential scanning probe) were compared, and the total accuracy of uT by ERUS was 74%. The accuracy of each stage was: T1 93%; T2 84%; T3 83%; T4 88%. The accuracy of the two probes in the diagnosis of rectal cancer at different positions were as follows: that of straight convex probe at the upper position was 60%, the middle positon was 75%, and the lower position was 73%. And that of circumferential scanning probe at the upper position was 73%, the middle positon was 75% and the lower position was 75%. Conclusion:　The two probes are both of great importance for preoperative uT of rectal cancer. For the preoperative diagnosis of rectal cancer at different positions, the accuracy rate of circumferential scanning probe is slightly higher than that of straight convex probe. Based on the actual situation, choosing the appropriate probe or using two probes in combination can improve the accuracy of preoperative staging and provide a good basis for the treatment.

Abstract:Objective:　To explore the key techniques and molecular mechanism of the treatment of allergic rhinitis (AR) by nasal mound and inferior turbinate cutting therapy. Methods:　From March 2, 2019 to May 30, 2020, the clinical data of 85 patients with AR in Hospital of Chengdu University of Traditional Chinese Medicine were collected, including 32 males and 53 females, aged 35.74±10.24. A visual analogue scale (VAS) score was used to compare the efficacy of different cutting sites, cutting directions and cutting depth at 1 week, 4, 8 and 12 weeks after treatment. The levels of interferon-gamma (IFN-γ), immunoglobulin E (IgE) and inter-leukin-4 (IL-4) in serum of patients before and after treatment were further detected by ELISA. Eosinophils and mastocyte of pa-tients before and after treatment were detected by HE staining and toluidine blue staining. The expression levels of Calcitonin gene related peptide (CGRP) and substance P (SP) were detected by Western blot and qPCR. Statistical analysis was performed with SPSS 22.0. Results:　The curative effect of nasal mound combined with inferior turbinate was significantly better than that of simple nasal mound turbinate and simple inferior turbinate (P<0.05). There was no significant difference in efficacy among the three directions of nasal mound turbinate. The results of ELISA showed that the levels of IFN-γ (t=6.069, P<0.001) in AR patients after treatment were significantly increased, IgE (t=6.954, P<0.001) and IL-4 (t=12.060, P<0.001) were evidently decreased. HE staining and toluidine blue staining indicated a significant decrease in eosinophil infiltration and mastocyte activity in the treated patients. Western blot experiment showed that CGRP (t=11.130, P=0.008) and SP (t=11.930, P=0.007) decreased significantly after treatment in AR patients compared with those before treatment. The qPCR experiment showed that CGRP (t=11.640, P=0.007) and SP (t=7.104, P=0.002) decreased significantly after treatment in AR patients compared with those before treatment. Conclusion:　The site and depth of the cutting are the key technical parameters for the therapy of nasal mound and inferior turbinate cutting, which can reduce the inflammation of nasal mucosa, and its molecular mechanism maybe reduced expression of CGRP and SP.

Abstract:Objective:　To screen potential molecular markers of cervical cancer cells by ultra-high speed cell sorting platform combined with cDNA microarray technology. Methods:　In this paper, the MoFlo XDP-type ultra-high-speed cell selection platform was used to purify cervical cancer cells expressing CD38 and not expressing CD38 on the cell membrane surface. RNAlater technology was used to obtain the RNA required for cDNA microarray experiments, and then by gene chip analysis was made. Results:　The MoFlo XDP-type ultra-high-speed cell selection platform can be used to obtain cervical cancer cells with a CD38-positive expression of 99.0% purity. Conclusion:　Through the analysis of cDNA microarray, potential molecular markers of cervical cancer cells such as RORA, PLIN4, AUTS2, and IFITM1 have been found, which provides a new technical method for the research of cervical cancer.

Abstract:Objective:　To analyze the effect of pars plana vitrectormy (PPV) on visual acuity of posterior intraocular foreign body. Methods:　Retrospective analysis was made in 40 cases of posterior segment intraocular foreign bodies (40 eyes, all in posterior segment intraocular foreign bodies by 23G minimally invasive PPV) admitted to the Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University from December 2015 to January 2017. We studied such following factors as age, gender, preoperative/postoperative best corrected visual acuity (BCVA), posterior segment foreign material properties, size, intraocular foreign body removal time, position of intraocular foreign bodies, intraocular foreign bodies left position, operation time, operation method and complications in the statistics. Results:　The 40 foreign bodies were all taken out, and the probability was 100%. The average BCVA after operation was significantly better than that before the operation (t=4.295, P=0.000). The main influencing factors for the vision of patients were retinal detachment (P=0.000), the retina injury (P=0.001), the size of the intraocular foreign bodies (P=0.023), the time of removing the foreign bodies (P=0.006), hyphema (P=0.032), and vitreous hemorrhage (P=0.025). Conclusion:　Greater intraocular foreign bodies and combination of retinal detachment, retinal hiatus, hyphema, vitreous hemorrhage, the time of removing foreign bodies longer in the open in trauma can cause more serious consequences, and worse prognosis of eyesight. In our study, whether stage Ⅰ suture + intravitreal infusion or direct vitrectomy combined with ocular debridement and suture had no significant impact on the recovery of vision and anatomy. But vitrectomy can better remove intraocular foreign body complicated with intraocular complications, and timely treatment plays an important role in the recovery of visual acuity for patients.

Abstract:Objective:　To investigate the factors influencing hysterectomy on patients with placenta accreta spectrum disorders (PAS), explore the best treatment of PAS, and reduce the proportion of hysterectomy. Methods:　A retrospective study was conducted among 269 pregnant women who diagnosed with PAS and underwent cesarean section (CS) between January 1, 2015 and December 31, 2021 in Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, and they were divided into hysterectomy group (study group) and non-hysterectomy group (control group). The related factors of hysterectomy were compared between the two groups, including basic characteristics, antepartum hemorrhage (early pregnancy bleeding, bleeding in the second and third trimester of pregnancy), type of placenta accreta, pernicious placenta previa (PPP), pregnancy complications (gestational hypertension, gestational diabetes, intrahepatic cholestasis of pregnancy), image diagnosis of PAS before the operation (ultrasound or nuclear magnetic reso-nance), abdominal aorta balloon occlusion, emergency CS, infant birth weight, position of fetus, and so on. Univariate and multivariate logistic analyses were used for statistical analysis. Results:　There were significant differences between the two groups in pregnancy times, parity, previous CS times, intrauterine adhesion history, second and third trimester bleeding, PPP, preoperative imaging diagnosis of placenta accreta, abdominal aortic balloon occlusion, gestational age and newborn weight (P<0.05). In multivariate logistic analysis, history of interuterine adhesions, type of placenta accreta and PPP were independent risk factors affecting hysterectomy (OR>1, P<0.05), and middle and late antepartum hemorrhage and CS were independent protective variables affecting hysterectomy (OR<1, P<0.05). Conclusion:　Women with PAS complicated with history of interuterine adhesions, PPP and more extent of placenta accreta have significantly higher risks of hysterectomy than women without hysterectomy, and middle and late antepartum hemorrhage and longer gestational age can reduce the risk of hysterectomy.

Abstract:Objective:　To investigate the relationship between primary hepatocellular carcinoma (HCC) and the expression of circadian genes. Methods:　The profiles containing 424 samples were downloaded from The Cancer Genome Atlas (TCGA) of the United States, including 374 cases of hepatoma samples and 50 cases of normal samples. Fifty-one circadian genes were analyzed by DECenter, so as to obtain the differentially expressed genes (DEGs). The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were performed by DAVID online analyses. The protein-protein interaction (PPI) networks of the DEGs were constructed through the STRING database. The circadian genes were studied on its main role in the occurrence and development of HCC. Results:　A total of 51 DEGs were identified from 374 cases, among which 21 genes were upregulated (P<0.05) and 3 genes were downregulated (P<0.05). DEGs were mainly involved in the Wnt signaling pathway, Hedgehog signaling pathway and Hippo signaling pathway (P<0.001). Ten DEGs involving in circadian rhythm and regulation of metabolic process were closely associated in the PPI network (P<0.001). GO analysis showed that the biological functions of DEGs focused primarily on circadian rhythm, regulation of metabolic process and regulation of gene expression (P<0.001). Conclusion:　DEGs participate in the development of primary HCC through the pathway of circadian rhythm and cell metabolism.

Abstract:Arginine vasopressin (AVP) is a hormone synthesized from the hypothalamus in response to increased plasma osmotic pressure and decreased blood volume, which influences glucolipid metabolism by binding to AVP receptors. Recent studies show that Copeptin, co-secreted with AVP in equimolar amounts, is considered stabilized, sensitive and not bioactive surrogate marker of AVP. Elevated plasma levels of Copeptin are essentially associated with diabetes, diabetic complications, obesity, insulin resistance, hyper-tension, hyperlipidemia, non-alcoholic fatty liver disease and other metabolic diseases. Therefore, exploring the relationship between Copeptin and metabolic diseases actively will contribute to the early diagnosis of related diseases.

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