Establishment and behavioral evaluation of a mouse model of long-term free-choice alcohol drinking / 北京大学学报(医学版)

OBJECTIVE@#To establish a model of long-term free drinking mouse by feeding mice with alcohol to simulate the state of human voluntary long-term drinking, and on this basis, to further discuss the evaluation criteria of long-term free drinking mice model in sports, anxiety and cognitive behavior.@*METHODS@#Forty six-week-old SPF C57BL/6 male mouse were randomly divided into two groups: Long-term free drinking group (n=20) and normal control group (n=20). The two groups were given solid feed normally. The long-term free drinking group was free to take 10% alcohol and water every day, while the normal drinking group only took water every day. The mice were fed for 7 months, and were evaluated by a series of behavioral methods, including Rota-rod test, balance beam test, open filed test, the elevated plus maze, two-box social behavior, new object recognition, Y maze and water maze.@*RESULTS@#With the increase of drinking days, the mice showed significant alcohol addiction in the alcohol preference test. With the increase of alcohol intake, the mice in the long-term free choice drinking group had slightly shiny fur and reduced diet. Compared with the control group, the weight gain began to slow down from the third month, and the weight decreased significantly by the sixth and seventh months (P=0.006, P < 0.001). The mice showed reduced balance locomotion ability (P=0.003, P=0.001) in the rotary bar and balance beam test. In the open field and elevated cross test, the mice had obvious anxiety-like behavior (P < 0.001). The mice showed decreased social ability in the two boxes of social behavior (P < 0.016). In the experiment of new object recognition and Y maze, the exploration of new object decreased (P=0.018, P=0.040). In the water maze, cognitive functions, such as learning and spatial memory were reduced (P < 0.001).@*CONCLUSION@#The successful establishment of the long-term free drinking mouse model is more convenient for us to carry out further research on the neural mechanism of alcohol addiction, and lays an experimental foundation for exploring the neural mechanism of alcohol addiction and related new targets.

Effects of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy treatment in patients with untreated gastric cancer with peritoneal metastasis / 中华胃肠外科杂志

Objective: To investigate the efficacy of laparoscopic hyperthermic intraperitoneal perfusion chemotherapy combined with intraperitoneal and systemic chemotherapy (HIPEC-IP-IV) in the treatment of peritoneal metastases from gastric cancer (GCPM). Methods: This was a descriptive case series study. Indications for HIPEC-IP-IV treatment include: (1) pathologically confirmed gastric or esophagogastric junction adenocarcinoma; (2) age 20-85 years; (3) peritoneal metastases as the sole form of Stage IV disease, confirmed by computed tomography, laparoscopic exploration, ascites or peritoneal lavage fluid cytology; and (4) Eastern Cooperative Oncology Group performance status 0-1. Contraindications include: (1) routine blood tests, liver and renal function, and electrocardiogram showing no contraindications to chemotherapy; (2) no serious cardiopulmonary dysfunction; and (3) no intestinal obstruction or peritoneal adhesions. According to the above criteria, data of patients with GCPM who had undergone laparoscopic exploration and HIPEC from June 2015 to March 2021 in the Peking University Cancer Hospital Gastrointestinal Center were analyzed, after excluding those who had received antitumor medical or surgical treatment. Two weeks after laparoscopic exploration and HIPEC, the patients received intraperitoneal and systemic chemotherapy. They were evaluated every two to four cycles. Surgery was considered if the treatment was effective, as shown by achieving stable disease or a partial or complete response and negative cytology. The primary outcomes were surgical conversion rate, R0 resection rate, and overall survival. Results: Sixty-nine previously untreated patients with GCPM had undergone HIPEC-IP-IV, including 43 men and 26 women; with a median age of 59 (24-83) years. The median PCI was 10 (1-39). Thirteen patients (18.8%) underwent surgery after HIPEC-IP-IV, R0 being achieved in nine of them (13.0%). The median overall survival (OS) was 16.1 months. The median OS of patients with massive or moderate ascites and little or no ascites were 6.6 and 17.9 months, respectively (P<0.001). The median OS of patients who had undergone R0 surgery, non-R0 surgery, and no surgery were 32.8, 8.0, and 14.9 months, respectively (P=0.007). Conclusions: HIPEC-IP-IV is a feasible treatment protocol for GCPM. Patients with massive or moderate ascites have a poor prognosis. Candidates for surgery should be selected carefully from those in whom treatment has been effective and R0 should be aimed for.

Standardized diagnosis and treatment and quality control of gastric cancer / 中华消化外科杂志

Gastric cancer is one of the common malignant tumors of the digestive system. The data from China Gastrointestinal Cancer Surgical Alliance suggests that there are great differences in the incidence of gastric cancer, the distribution of tumors in different stages and level of diagnosis and treatment in different regions of our country, and there are some differences in the data records of different medical centers. Therefore, it is very important to implement the standardized diagnosis and treatment and quality control of gastric cancer, to establish a standardized gastric cancer data-base, and to promote the standardization, homogenization and standardization of the diagnosis and treatment of gastric cancer in the country. As a result, the Expert Committee of Quality Control of Gastric Cancer of the National Cancer Quality Control Center drafts and formulates the Quality Control Index for Standardized Diagnosis and Treatment of Gastric Cancer in China (2022 Edition), in which the quality control index includes the aspects of imaging examination, pathological diagnosis, surgical treatment, drug therapy, radiotherapy and postoperative quality control of gastric cancer. The authors give a thorough elaboration on the lymph node dissection scope, standardization and quality control of postoperative lymph node detection and construction of database of gastric cancer.

Identification of Plasma Biomarkers in Drug-Naïve Schizophrenia Using Targeted Metabolomics

Objective@#Schizophrenia (SCZ) is a severe psychiatric disorder with unknown etiology and lacking specific biomarkers. Herein, we aimed to explore plasma biomarkers relevant to SCZ using targeted metabolomics. @*Methods@#Sixty drug-naïve SCZ patients and 36 healthy controls were recruited. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. We analyzed the levels of 271 metabolites in plasma samples from all subjects using targeted metabolomics, and identified metabolites that differed significantly between the two groups. Then we evaluated the diagnostic power of the metabolites based on receiver operating characteristic curves, and explored metabolites associated with the psychotic symptoms in SCZ patients. @*Results@#Twenty-six metabolites showed significant differences between SCZ patients and healthy controls. Among them, 12 metabolites were phosphatidylcholines and cortisol, ceramide (d18:1/22:0), acetylcarnitine, and γ-aminobutyric acid, which could significantly distinguish SCZ from healthy controls with the area under the curve (AUC) above 0.7. Further, a panel consisting of the above 4 metabolites had an excellent performance with an AUC of 0.867. In SCZ patients, phosphatidylcholines were positively related with positive symptoms, and cholic acid was positively associated with negative symptoms. @*Conclusion@#Our study provides insights into the metabolite alterations associated with SCZ and potential biomarkers for its diagnosis and symptom severity assessment.

Four-Hour Fasting for Semifluids and 2-Hour Fasting for Water Improves the Patient Experience of Esophagogastroduodenoscopy: A Randomized Controlled Trial

Background/Aims@#We aimed to investigate the comfort, safety, and endoscopic visibility during esophagogastroduodenoscopy (EGD) afforded by a modified 4-hour semifluid and 2-hour water (“4+2”) fasting protocol. @*Methods@#In this parallel group, endoscopist-blinded, randomized controlled trial, outpatients undergoing unsedated diagnostic EGD from 10:30 AM to 12:00 PM were randomly assigned to either a “4+2” protocol group or a conventional fasting group. The participants’ comfort during the fasting period and procedure was measured using the visual analog scale, and mucosal visibility was measured by endoscopists using the total visibility score. Satisfaction was defined as a visual analog scale score of ≤3. The primary outcome was the participants’ comfort during fasting. @*Results@#One hundred and six and 108 participants were randomized to the “4+2” protocol and control groups, respectively. Participants’ comfort before EGD was significantly higher in the “4+2” protocol group measured by both the proportion of satisfaction (86.8% vs 63.9%, p=0.002) and the visual analog scale score (median [interquartile range]: 1.0 [1.0–2.0] vs 3.0 [1.0–4.0], p<0.001). The proportion of satisfaction during EGD also significantly improved (59.4% vs 45.4%, p=0.039) in the “4+2” protocol group. The total visibility score was unaffected by the fasting protocol (5.0 [4.0–5.0] vs 4.0 [4.0–5.0], p=0.266). No adverse events were observed during the study. @*Conclusions@#The “4+2” protocol was more comfortable and provided equal mucosal visibility and safety compared with conventional fasting for unsedated EGD.

Discovery of a highly potent and orally available importin-β1 inhibitor that overcomes enzalutamide-resistance in advanced prostate cancer

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

CiteSpace knowledge map of research status and trends of Croci Stigma / 中国中药杂志

This study retrieved Croci Stigma related literature from CNKI, Wanfang, VIP, and Web of Science database, and used bibliometrics and CiteSpace 6.1.R2 software to analyze the published Croci Stigma related articles in Chinese and English from 2000 to 2022. The authors, research institutions, and keywords were visualized and analyzed, and the current status and development trend of Croci Stigma research was summarized by combining the information extraction methods. A total of 1 846 Chinese articles and 2 703 English articles were screened out and included. The results showed a generally steady increase in the number of Croci Stigma related articles. The results of the visualization analysis showed that there were more collaborations between researcher teams and major research institutions in English articles than Chinese articles. The Chinese articles was mainly published by China Pharmaceutical University, and most of the inter-institutional collaborations occurred in neighboring regions. The English articles was mainly published by Iranian institutions, and most of the cooperation occurred within the country, with less transnational cooperation. Keywords analysis showed that the research on Croci Stigma was mainly focused on chemical compositions, pharmacological effects, mechanisms, quality control, etc. It was predicted that the future research hotspots of Croci Stigma would mainly focus on pharmacological mechanism and clinical efficacy. The current research related to Croci Stigma still needs to be developed, cooperation should be strengthened, and more in-depth research should be conducted.

Study on preparation of poly-Carboxyhemoglobin by glutaraldehyde crosslinking / 中国输血杂志

【Objective】 To investigate the preparation conditions of hemoglobin-based oxygen carrier (HBOC) at room temperature without oxygen isolation and the quality of poly-COHb. 【Methods】 Using human cord blood hemoglobin as raw material and glutaraldehyde as crosslinking agent, the experimental group selected hemoglobin concentration, glutaraldehyde to COHb molar ratio, reaction time and reaction temperature to do four factors and three levels of orthogonal test (n=3), to determine the best matching conditions and prepare three batches of poly-COHb, continuously.In the control, 3 batches of poly-Hb were prepared under low temperature and oxygen isolation.The contents of superlarge molecules, degree of polymerization, average molecular weight, methemoglobin and P50 of crosslinked products were compared between the two groups. 【Results】 The optimal matching conditions of poly-COHb were as follows: [Hb] 70g/L, the molar ratio of glutaraldehyde to COHb was 11∶1, the reaction time was 60 min, and the reaction temperature was 25℃.Comparison of poly-COHb and poly-Hb: The superlarge molecular content (%) was 0.67±0.51 vs 0.60±0.01 (P>0.05); degree of polymerization (%) and average molecular weight (kD) were 84.25±0.99 vs 54.16±5.12, and 235.27±13.50 vs 97.62±6.57, respectively.(P<0.05); methemohemoglobin ratio (%) was 2.40±0.66 vs 2.47±0.46 (P>0.05); P50 (mmHg) was 6.37±0.30 vs 14.20±1.09 (P<0.05). 【Conclusion】 Poly-COHb can be prepared at room temperature without oxygen isolation.Compared with poly-Hb, poly-COHb prepared under the experimental conditions can improve the polymerization degree and average molecular weight, and greatly reduce the difficulty of preparation.

Preparation of a novel double polymerized of red blood cell substitute and preliminary observation of its curative effect / 中国输血杂志

【Objective】 To study the red blood cell substitute preparation method of glutaraldehyde(GDA) and Bis(3, 5-dibromosalicyl) fumarate(DBBF) double polymerized, and also observe its curative effect. 【Methods】 The affecting factors of the crosslink of DBBF and human placental hemoglobin(Hb) were selected, including solution pH, inositol hexaphosphoric acid concentration, and molar ratios of DBBF/Hb. The changes of P50, Hill Co and methemoglobin(MetHb) content during the preparation process were studied and the molar ratio of GDA to DBBF-Hb were determined. The final product was obtained through the steps of ultrafiltration, filtration, and deoxygenation, etc., and the final product was subjected to a study on the curative effect of anti-hemorrhagic shock in rats. 【Results】 Under the condition of pH 8.0, the concentration of inositol hexaphosphoric acid was 10mM/L, the molar ratio of DBBF/hemoglobin was 6∶1, the content of dimer was(22.67±3.28)%, the content of tetramer was (74.64±7.05)%, and its P50 was (25.25±2.31) mmHg. As the molar ratio of DBBF/Hb increased, P50 and MetHb content would gradually increase, while the Hill Co will gradually decrease. The molar ratio of GDA and DBBF-Hb was 7∶1, the content of dimer was (8.23±0.79)%, the content of tetramer was (27.87±3.63)%, the content of super-macromolecule was (1.05±0.31)%. As the molar ratio of GDA and DBBF/Hb increased, MetHb content would increase, while the P50 and Hill Co would gradually decrease. The 24h survival rate of the product in rats with hemorrhagic shock was 83.33%(10/12), which was significantly higher than that in the negative control group[41.67%(5/12)], while similar with the positive control group [91.67%(11/12)]. 【Conclusion】 The red blood cell substitutes with GDA and DBBF double polymerized can effectively reduce the dimer content, which is more conducive to industrial production, and has a positive effect on the treatment of hemorrhagic shock.

A case report of right ureteral stenosis caused by pelvic desmoid-type fibromatosis / 中华泌尿外科杂志

Desmoid-type fibromatosis is a rare benign tumor with invasive growth, which can occur in all parts of the body, mostly in the abdominal wall, and also in the abdomen and skeletal muscle. This paper reports a case of right ureteral stenosis caused by pelvic desmoid-type fibromatosis. Pelvic tumor resection, ileocecal resection and ureterovesical replantation were performed. The patients were followed up for 18 months without local recurrence and distant metastasis.

Analysis of factors associated with the duration of chest compression pause time during the manual-mechanical conversion process in cardiopulmonary resuscitation / 中华急诊医学杂志

Objective:To analyze the factors related to the duration of chest compression pause time during the manual-mechanical conversion process in cardiopulmonary resuscitation (CRP).Methods:A retrospective study was devised in a cohort comprising patients with out-of-hospital cardiac arrest, who were assigned to receive mechanical CRP in the Department of Emergency of Huzhou First People's Hospital from January 2019 to December 2020. Patient’s general characteristics, CRP data and data on CRP-free intervals were collected multiple linear regression to analyze associations with the duration of chest compression pause time during the manual-mechanical conversion process in CRP. At the same time, the effect of CPR treatment qualification of nurses on CPR compression quality was evaluated.Results:The study selected 32 eligible patients. Patient's height, actual body weight, and body mass index showed a positive liner correlation with the duration of chest compression pause time ( r=0.61, 0.92, 0.49; P<0.01). Multiple stepwise regression analysis showed that actual body weight was an independent risk factor for prolonged duration of chest compression pause time ( P<0.01). Moreover, responsible nurses with advanced cardiac life support (ACLS) certification had significantly higher compression scores than those without ACLS certification (χ 2=0.002, P<0.01). Conclusions:The actual body weight of patients and the ACLS qualification of nurses on duty have a certain relationship with the duration of chest compression pause time during the manual-mechanical conversion process in CRP, which is worthy of further research.

Repair effect and mechanism of neural cell adhesion molecule derived peptide P2 on nerve function injury in ischemic stroke rats / 中华行为医学与脑科学杂志

Objective:To clarify the neuroprotective effects of neural cell adhesion molecule (NCAM) derived peptide P2 on in vitro cultured neuron and ischemic stroke rat. Methods:Primary cortical neurons were extracted and cultured, and CCK-8 method was used to observe the protective effect of different concentrations of P2 on cortical neurons under oxygen-glucose deprivation (OGD) conditions.The levels of apoptosis-related proteins and extracellular signal regulated kinase 1/2 (Erk1/2) were observed by Western blot. Clean grade male SD rats were selected for animal experiments. The middle cerebral artery occlusion (MCAO) method was used to establish the rat model of cerebral ischemia/reperfusion injury. The rats with successful model were divided into sham operation group, MCAO group and MCAO+ P2 group according to the random number table, with 12 rats in each group. After operation, rats in MCAO+ P2 group were subcutaneously injected with 1 mg/kg P2 once a day until 14 days after operation, and rats in the other two groups were subcutaneously injected with 0.9% sodium chloride solution of the same volume.Beam-walking test was used to evaluate the motor function of rats.Immunofluorescence staining and Western blot were used to detect the in-situ apoptosis of neuronal cells and the expression of Erk1/2 in ischemic penumbra of rat brains, respectively. All statistical analyses were performed using SPSS 22.0.Repeated measurement ANOVA was used to evaluate the beam-walking experimental data, and one-way ANOVA were used to analyze other experimental data among multiple groups.Results:Compared with OGD group, 0.5, 1.0 and 2.0 μmol/L P2 improved the activity of neurons under OGD conditions, of which 1 μmol/L P2 had the best effect ((2.436±0.284), (1.551±0.410), P<0.05). Western blot showed that the protein levels of bax ((76.120±3.232)%, (88.965±5.208)%, P<0.05), cleaved caspase-3 ((76.736±4.306)%, (97.781±8.111)%, P<0.05) and cleaved caspase-9 ((88.833±6.581)%, (104.962±4.788)%, P<0.05) in 1 μmol/L P2 treated group were all lower than those in OGD group, while the protein levels of bcl-2 ((56.146±3.882)%, (43.170±6.945)%, P<0.05) and phosphorylated Erk1/2 ((73.583±8.557)%, (55. 219±4.615)%, P<0.05) in 1 μmol/L P2 treated group were both higher than those in OGD group. Compared with MCAO group, on the 14th day after P2 intervention, the slip ratio of hindlimb of the paralyzed hind limbs of rats was lower ((23.438±11.540)%, (41.733±13.631)%, P<0.05), the apoptosis rate of neurons around the focus was lower ((13.144±6.485)%, (26. 699±6. 402)%, P<0.05), and the level of phosphorylated Erk1/2 protein in the brain tissues around the infarct focus was higher ((74.062±7.458)%, (53.327±7.093)%, P<0.05). Conclusion:Low doses of neural cell adhesion molecule derived peptide P2 exert neuroprotective effects on OGD neurons and ischemic stroke rats. The underlying mechanism may be related to the activation of Erk.

China guideline for the screening, early detection and early treatment of gastric cancer (2022, Beijing) / 中华肿瘤杂志

Gastric cancer (GC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demons-trated that screening, early detection and early treatment are effective in reducing the incidence and mortality of GC. The development of the guideline for GC screening, early detection and early treatment in line with epidemic characteristics of GC in China will greatly promote the homogeneity and standardization, and improve the effect of GC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of GC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of GC screening and provide scientific evidence for the GC prevention and control in China.

China guideline for the screening, early detection and early treatment of esophageal cancer (2022, Beijing) / 中华肿瘤杂志

Esophageal cancer (EC) is a major digestive tract malignancy in China, which seriously threatens the health of Chinese population. A large number of researches have demonstrated that screening and early detection are effective in reducing the incidence and mortality of EC. The development of the guideline for EC screening and early detection in line with epidemic characteristics of EC in China will greatly promote the homogeneity and standardization, and improve the effect of EC screening. This guideline was commissioned by the Bureau of Disease Control and Prevention of the National Health Commission. The National Cancer Center of China initiated and convened a working group comprising multidisciplinary experts. Following the World Health Organization Handbook for Guideline Development, this guideline combined the most up-to-date evidence of EC screening, China's national conditions, and practical experience in cancer screening. This guideline provided evidence-based recommendations with respect to the screening population, technology and procedure management, aiming to improve the effect of EC screening and provide scientific evidence for the EC prevention and control in China.

Combination of 18 F-Fluorodeoxyglucose PET/CT Radiomics and Clinical Features for Predicting Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma

Objective@#To identify epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma based on 18 F-fluorodeoxyglucose (FDG) PET/CT radiomics and clinical features and to distinguish EGFR exon 19 deletion (19 del) and exon 21 L858R missense (21 L858R) mutations using FDG PET/CT radiomics. @*Materials and Methods@#We retrospectively analyzed 179 patients with lung adenocarcinoma. They were randomly assigned to training (n = 125) and testing (n = 54) cohorts in a 7:3 ratio. A total of 2632 radiomics features were extracted from the tumor region of interest from the PET (1316) and CT (1316) images. Six PET/CT radiomics features that remained after the feature selection step were used to calculate the radiomics model score (rad-score). Subsequently, a combined clinical and radiomics model was constructed based on sex, smoking history, tumor diameter, and rad-score. The performance of the combined model in identifying EGFR mutations was assessed using a receiver operating characteristic (ROC) curve. Furthermore, in a subsample of 99 patients, a PET/CT radiomics model for distinguishing 19 del and 21 L858R EGFR mutational subtypes was established, and its performance was evaluated. @*Results@#The area under the ROC curve (AUROC) and accuracy of the combined clinical and PET/CT radiomics models were 0.882 and 81.6%, respectively, in the training cohort and 0.837 and 74.1%, respectively, in the testing cohort. The AUROC and accuracy of the radiomics model for distinguishing between 19 del and 21 L858R EGFR mutational subtypes were 0.708 and 66.7%, respectively, in the training cohort and 0.652 and 56.7%, respectively, in the testing cohort. @*Conclusion@#The combined clinical and PET/CT radiomics model could identify the EGFR mutational status in lung adenocarcinoma with moderate accuracy. However, distinguishing between EGFR 19 del and 21 L858R mutational subtypes was more challenging using PET/CT radiomics.

Comparison of sitagliptin and acarbose in patients with type 2 diabetes mellitus complicated with sarcopenia / 中国医师进修杂志

Objective:To observe the changes of skeletal muscle indexes in elderly patients with type 2 diabetes complicated with sarcopenia treated with sitagliptin and acarbose.Methods:A total of 60 patients over 60 years old with type 2 diabetes complicated with sarcopenia in Dalian Municipal Central Hospital from January 2019 to January 2020 were selected and divided into two groups by random number table method.One group received sitagliptin and metformin,and the other group received acarbose and metformin. The changes of skeletal muscle indexes, glucagon-like peptides-1 (GLP-1), insulin resistance index (HOMA-IR) and inflammatory indexes were compared between the two groups at baseline and 36 weeks after treatment.Results:After treatment, the skeletal muscle index (SMI) of sitagliptin group was increased (5.94 ± 1.52 vs. 5.99 ± 1.52), and the difference was statistically significant ( P<0.05). Muscle strength and SMI decreased in acarbosse group (18.75 ± 4.64 vs. 17.72 ± 4.44, 6.09 ± 1.74 vs. 6.00 ± 1.71), with statistical significance ( P<0.05). GLP-1 increased in sitagliptin group, 0 min: (10.65 ± 1.68) pmol/L vs. (12.41 ± 1.88) pmol/L; 60 min: (22.79 ± 2.85) pmol/L vs. (25.51 ± 2.79) pmol/L; 120 min: (24.26 ± 2.94) pmol/L vs. (29.49 ± 2.91) pmol/L; 180 min: (11.68 ± 1.84) pmol/L vs. (12.88 ± 1.83) pmol/L. There were significant differences ( P<0.05). HOMA-IR and CRP decreased: 4.73 ± 3.04 vs. 3.16 ± 2.41, (2.39 ± 0.50) mg/L vs. (2.33 ± 0.43) mg/L, and the differences were statistically significant ( P<0.05). HOMA-IR in acarbose group decreased after treatment (5.80 ± 3.94 vs. 4.00 ± 1.63), and the difference was statistically significant ( P<0.05). Comparison between the two groups after treatment, the decreased value of muscle strength in sitagliptin group was less than that in acarbose group, and the difference was statistically significant ( P<0.05). GLP-1 and overall GLP-1 area under the curve in sitagliptin group were higher than those in acarbose group (67.64 ± 6.81 vs. 58.98 ± 6.72), with statistical significance ( P<0.05). HOMA-IR and CRP in sitagliptin group were lower than those in acarborose group: 3.16 ± 2.42 vs. 4.00 ± 1.63, (2.33 ± 0.43) mg/L vs. (2.41 ± 0.70) mg/L, with statistical significances ( P<0.05). Conclusions:Sitagliptin therapy improves muscle mass and protects muscle strength in elderly patients with type 2 diabetes mellitus and sarcopenia.

Treatment options for colorectal cancer primary lesions with unresectable metastases at risk of acute abdomen / 国际肿瘤学杂志

For patients with metastatic colorectal cancer, it is still controversial whether the primary tumor needs surgery when the metastasis is unresectable. The effect of palliative surgical resection of the primary lesion on improving the prognosis and prolonging survival is still uncertain while the risks of acute abdomen trigger the discussion of early palliative surgical resection of the primary tumor. Evaluating and predicting the risk of acute abdomen complicated by colorectal cancer will help to choose the treatment of the primary lesion of unresectable metastatic colorectal cancer.

Efect of PolyCHb on enhancing tissue oxygen supply and the treatment of remvatinib for liver cancer graft: Preliminary observation / 中国输血杂志

【Objective】 To investigate the effect of Polymerized human cord hemoglobin (PolyCHb) on the sensitivity of hepatocellular carcinoma grafts to lumvalatinib in nude mice. 【Methods】 Hep3B hepatoma cells were subcutaneously transplanted in 18 nude mice to establish tumor graft model. Mice were randomly divided into 3 groups: control group (the saline 90 mg·kg-1·d-1), monotherapy group (Lenvatinib10 mg·kg-1·d-1), and sensitized group (Lenvatinib mg·kg-1·d-1, polyCHB 600 mg/kg twice a week) for 28 days. The tumor volume was measured regularly and the growth curve was drawn. On day 29, the nude mice were sacrificed, the tumor was stripped and weighed, and the pathomorphological differences of each group were evaluated by HE section staining. The expression levels of hypoxia-inducing factor (HIF-1α), CD34, VEGF, CD44, MMP-9, and Glut-1 in tumor tissues of each group were determined by immunohistochemistry. The content of reactive oxygen species (ROS) in tumor tissues of each group was determined by dihydroethyl ingot method. 【Results】 The tumor growth rate and tumor volume in the sensitized group decreased significantly compared with the control group and the solo drug group. On day 29, the tumor volumes of the control group, the monotherapy group and the sensitization group were (2 076.46±350.25)mm3, (1 035.96±84.16)mm3 and (892.66±104.46)mm3, respectively. Tumor weight was (1.61±0.52)g, (0.45±0.10)g, and (0.34±0.13)g, respectively. Immunohistochemical score of HIF-1α was 75±23 vs 45±18 vs 18±11, VEGF was 52±8 vs 67±16 vs 35±4, CD34 was 40±7 vs 50±13 vs 28±7, CD44 was 37±15 vs 30±7 vs 15±3, Glut-1 was 74±41 vs 51±30 vs 14±18, MMP-9 was 51±7 vs 62±20 vs 33±3, respectively(P<0.05). The malignant degree of the sensitized group was decreased by HE section staining, which was significantly lower than that of the solo drug group and the control. The ROS content in the sensitized group was higher than that in the solo drug group and the control. 【Conclusion】 PolyCHb can reduce the expression of HIF-1α and its downstream pathway related molecules by increasing oxygenation of hepatocellular carcinoma tissues in nude mice, delay tumor growth and reduce tumor volume in a certain period, thus increase the therapeutic effect of lenvalatinib on hepatocellular carcinoma grafts in tumor bearing nude mice models.

Protective effect of hemoglobin oxygen carrier with different oxygen affinity on isolated rat hearts / 中国输血杂志

【Objective】 To explore the protective effects of hemoglobin base on oxygen carries (HBOCs) with different oxygen affinity on isolated rat hearts. 【Methods】 Using Langendorff isolated heart perfusion model, 45 adult male SD rats (SPF grade), perfused with 30 min KH solution baseline, were randomly divided into sham operation group and control group: St. Thomas (STS) solution perfusion volume was 3mL/100g body weight; high P50 HBOCs group: [STS + high P50 HBOCs (P50=35.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3mL/100g body weight; medium P50 HBOCs group: [STS + medium P50HBOCs (P50=26.5.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3 mL/100 g body weight; low P50 HBOCs group: [STS + low P50 HBOCs (P50=11.0 mmHg, 2.5 mg/100 g) product] perfusion volume was 3mL/100g body weight, and the heart was arrested and placed in a 37℃ water bath to make the heart ischemic for 35 minutes, and then reperfused for 2 hours. The left ventricular development pressure (LVDevP), left ventricular end diastolic pressure (LVEDP), the rate of change of left ventricular pressure (LVPCR) and heart rate (HR) in the rat heart during reperfusion were observed and recorded. 1 min perfusion fluid from each rat in the basic and reperfusion phase was taken, and blood gas analyzer was used to measure the blood gas indexes of rats, and the myocardial injury marker enzymes [cardiac enzyme creatine kinase (CK-MB), lactate dehydrogenase (LDH) and the release of α-hydroxybutyrate dehydrogenase (α-HBDH)] were measured by ELISA kit. 【Results】 The cardiac function and the release of myocardial enzymes in the 5 groups of rats in the basal cardiac perfusion stage were similar (P>0.05). However, in the reperfusion stage, except for the insignificant changes in HR (P>0.05), the heart LVDevP (mmHg) of the three P50 HBOCs groups and the control group were 10.69±3.65 vs 8.50±2.88, 23.26 ±5.62 vs 8.50±2.88, 35.60±3.82 vs 8.50±2.88, LVEDP (mmHg) were 43.34±8.08 vs 54.64±7.42, 39.43±8.30 vs 54.64±7.42, 31.46±4.11 vs 54.64±7.42, dp/dt were 12.09±9.96 vs 6.09±0.98, 25.65±8.87 vs 6.08±0.98, 35.32±9.33 vs 6.09±0.98, -dp/dt were 17.53±11.28 vs 11.39±2.16, 28.80±13.70 vs 11.39±2.16, 43.36±3.83 vs 11.39±2.16, respectively (all P<0.05); the rebound situation and the release of CK-MB, LDH, and α-HBDH in the three P50 HBOCs groups were better than those in the control group (P<0.05). Among the three P50HBOCs products, the low P50HBOCs group had the best cardiac function indexes. The myocardial enzyme indexes of the high, medium and low HBOCs groups were CK-MB (ng/mL): 110.47±4.04, 90.2±2.46, 77.1±3.51; LDH (U/L): 162.23±7.71, 135.13±23.69, 92.20±4.21; a-HBDH (U/L): 228.00±8.03, 172.30±8.99, 131.00±2.02. 【Conclusion】 STS solution containing HBOCs products can improve the function of the reperfused heart at normal temperature ischemia for 35 min and 2 h reperfusion, and reduce heart damage. The STS solution containing low P50 HBOCs has the most obvious protective effect in rat isolated heart perfusion.

Effect of PolyCHb oxygen carrier on partial coagulation indexes in vitro / 中国输血杂志

【Objective】 To compare the similarities and differences of polymerized human cord hemoglobin (PolyCHb) and free hemoglobin (FHb) on partial coagulation indexes in vitro, so as to analyze the effect of PolyCHb on coagulation dysfunction. 【Methods】 Using normal saline, two concentrations of FHb and PolyCHb and 36% methemoglobin-containing PolyCHb to mix with fresh whole blood or plasma-rich plasma (PRP) in equal proportions, and incubate at 37°C for 30 minutes to detect prothrombin time (PT), activated partial thromboplastin time (APTT), coagulation factor Ⅱactivity (FⅡ∶C), coagulation factor Ⅴactivity (FⅤ∶C), coagulation factor Ⅷactivity (FⅧ∶C), coagulation factor Ⅸactivity (FⅨ∶C), von Willebrand factor (vWF) and platelet P-selectin (CD62P). 【Results】 1) NaCl group: PT(22.68±1.76) s; APTT(59.58±7.52) s; FⅡ∶C(45.91±3.27) %; FⅤ∶C(30.86±4.43) %; FⅧ∶C(41.32±12.94) %; FⅨ∶C(23.96±5.10) %; vWF (2.14±0.54) mg/L; CD62P(7.44±4.47) %. This group kept as a diluted control. 2) 2% FHb group compared with 7% FHb group: FⅧ∶C (42.16±12.31) %vs (56.64±12.22 ) % (P0.05). 3) There is no significant difference between 2% PolyCHb group and 7% PolyCHb group (P>0.05). 4) There is no significant difference between 2% FHb group and 2% PolyCHb group (P>0.05). 5) 7% FHb group compared with 7% PolyCHb group: PT(23.31±1.34)s vs (21.97±1.56)s (P0.05). 6) 7% PolyCHb group Compared with Met-PolyCHb group: APTT(55.43±5.43) s vs (46.33±4.86)s (P0.05). 【Conclusion】 The effect of PolyCHb on coagulation markers is different from FHb. At the concentration of this study, PolyCHb will not cause coagulation disorders. However, if the methemoglobin (MetHb) content is too high, it will activate the intrinsic coagulation pathway.