Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68⁺ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

Objective:In order to provide the precise prevention and control strategy of drug resistance TB in Gansu province, we analyzed the status and risk factors of new drug resistance pulmonary tuberculosis patients.Methods:New pulmonary tuberculosis patients were enrolled from 30 tuberculosis-specialized medical institutions (drug resistance monitoring stations) in Gansu province between first September 2014 to 31 th August 2017, and filled in the survey questionnaire. The isolated Mycobacterium tuberculosis (MTB) strains were implemented 10 drugs drug- susceptibility tes, including isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), kanamycin (Km), amikacin (Am), ofloxacin (Ofx), capreomycin (Cm), propithio-iso-nicotinamide (Pto).The risk factors were analyzed by logistic regression model. Results:One patient was corresponding one clinical isolates among 1 815 patients. The rate (95% CI) of total drug-resistance, single drugresistance, multiple drug- resistance, multidrug-resistance and extensively drug-resistant were 25.45% (23.45%-27.46%), 11.40% (9.94%-12.87%),6.23% (5.11%-7.34%), 7.82% (6.59%-9.06%) and 0.28% (0.03%-0.52%) respectively. Among 142 multidrug-resistant TB patients, the farmers, young adults aged 20-59 and low-income group were 90.85%, 62.68% and 31.69%, respectively. The results of univariate and multivariate analysis showed that the male, non-Han, treatment less than 1 month group and treatment less than 1 month and withdrawal less than 2 month group were risk factors of new multidrug-resistant pulmonary TB. Conclusions:Compared with the Chinese national baseline level of TB resistance, the total drug resistance rate of new TB patients in Gansu province was low, but the multidrug-resistance rate was high. The health assistance for rural low-income TB patients was still an important strategy to prevent and control multidrug-resistant in Gansu province. And measures must implement to stop irregular treatment and poor compliance, as the risk factors of multidrug-resistance in new PTB patients.

Objective To evaluate the value of CT plus CTA in emergency surgical treatment of spontaneous intracerebral hemorrhage caused by brain arteriovenous malformations(AVM). Methods A total of 15 cases diagnosed with spontaneous intracerebral hemorrhage by emergent CT examination in the Second Affiliated Hospital of Wenzhou Medical University were retrospectively reviewed from May 2015 to June 2018, and subsequent emergent CTA examination was adopted to verify whether the patients had brain AVM that was responsible for the hemorrhage. After diagnosis, emergency surgical resection of the brain AVM and evacuation of hematoma were performed. Glasgow outcome score (GOS) was used to evaluated the outcome. A secondary DSA or CTA was performed from 2 weeks to 6 months post the operation. Results All 15 cases exanimated by emergent CT plus CTA were demonstrated to have brain AVM and intracranial hematoma. All the patients received emergency brain AVM resection and hematoma evacuation. The surgical finding during operation was in line with what was seen on emergent CT plus CTA, and all cases got total hematoma evacuation. Twelve cases received total brain AVM resection, and the other 3 cases received partial resection because the residual AVM foci existed in deep brain structures . After the operation, none had rebleeding at the surgical site. Follow-up DSA or CTA confirmed the 12 cases had total resection and the other 3 cases had partial resection. All patients were alive after the surgery and GOS scores during the follow-up time, from 2 weeks to 6 months after emergency surgery, were: 5 in 6 patients, 4 in 4 patients, 3 in 4 patients and 2 in 1 patient. Conclusions CT plus CTA can better show the relationship between vascular malformation, hematoma, and the adjacent anatomical structure, and therefore may contribute to intraoperative judgment and complete resection of vascular malformation. It is a practical imaging tool for the preoperative evaluation and emergency surgical treatment of spontaneous intracerebral hemorrhage caused by brain AVM.

Objective To investigate the curative efficacy of fracture with closed reduction and percutaneous Kirschner wire fixation of the simple lateral injury for humeral supracondylar fracture of Gartland type Ⅱ and type Ⅲ in children by the emergency treatment and selective surgery. Methods From March 2010 to March 2012,sixty children with Gartland type Ⅱ and type Ⅲ fresh humeral supracondylar fracture were operated in Xianyang Center Hospital. Six-ty children were randomly divided into two groups:group A by emergency operation 8 hours after injury with closed re-duction method and lateral percutaneous Kirschner wire fixation only,group B initially treated with plast fixation,then undergoing surgery after 3 - 5 days of injury with the closed reduction and percutaneous pin fixation. The operation du-ration,frequency of intraoperative image intensifier,postoperative swelling,pain lasting time after injury and hospitaliza-tion cost were investigated in two groups. Results The average operation duration of group A was(18. 5 ± 12. 3)min, and that in group B was(20. 1 ± 15. 3)min,and there was a statistically significant difference between two groups(P ﹤0. 05). The frequency of intraoperative image intensifier was 6. 2 times on the average in group A,but 7. 3 times in group B,and there was a statistically significant difference between two groups(P ﹤ 0. 05). The postoperative swelling rate on 3,5,7 days after injury in group B was significantly higher than that of group A,and there was a statistically sig-nificant difference(all P ﹤ 0. 05). The duration of pain after injury in group A was(3. 44 ± 1. 23)days,but(5. 26 ± 1. 36)days in group B,which was significantly different;the nerve function recovery time of group A was(36. 5 ± 7. 0) d,and it was(36. 2 ± 7. 0)d in group B,which was not significantly different(P ﹥ 0. 05). The average hospitalization time and cost in group A was less than that in group B,which was significantly different(P ﹤ 0. 05). Finally there was no statistically significant difference in elbow joint function between two groups of children(P ﹥ 0. 05). Conclusions The emergency operation of closed reduction and percutaneous Kirschner wire fixation for the treatment of simple lateral injury in children with Gartland type Ⅱ and type Ⅲ fracture has the advantages over the selective surgery,including shorter operation time,less contact of X - ray intraoperatively,light postoperative swelling,short duration of pain in chil-dren,as well as the shortened hospitalization time,reduced costs,especially good efficacy for joint function recovery.

Objective To report our method to determine lateral needle insertion point (intersection point skin marker) in closed reduction and percutaneous Kirschner wire fixation for pediatric supracondylar fracture of humerus.Methods From May 2012 to June 2014,125 children with supracondylar fracture of humerus were treated with closed reduction and percutaneous Kirschner wire fixation.Of them,60 did not use the intersection point method to determine the lateral needle insertion point (group A),including 46 boys and 14 girls,with an average age of 6.3 ±0.6 years.According to Gartland classification,28 cases were type Ⅱ and 32 cases type Ⅲ.In the other 65 children,the intersection point method was used to determine the lateral needle insertion point (group B),including 50 boys and 15 girls,with an average age of 6.4 ± O.9 years.According to Gartland classification,29 cases were type Ⅱ and 36 cases type Ⅲ.The 2 groups were compared in terms of operation time,fluoroscopy times,hospital stay and hospitalization cost.The efficacy was evaluated at the final follow-ups using Flynn criteria.The 2 groups were compatible without significant differences in preoperative general data (P ＞ 0.05).Results All the 125 children obtained successful closed reduction and percutaneous pin fixation,and an average follow-up of 13 months (from 12 to 15 months)as well.There were significant differences between groups A and B in average operation time (23.1 ± 15.3 min versus 17.5 ± 10.3 min) and fluoroscopy times (9.2 ± 1.0 times versus 5.3 ± 1.3 times) (P ＜ 0.05).There was no statistically significant difference between the 2 groups either in Flynn excellent to good rate [(98.3％ (59/60) versus 98.5％ (64/65)] (P ＞ O.05).Needle irritation occurred in 2 cases and Kirschner wire shift in one in group A while tensile blistering occurred in one in group B.Conclusion In closed reduction and percutaneous Kirschner wire fixation for pediatric supracondylar fracture of humerus,the intersection point skin marker is a simple and reliable method to determine the lateral needle insertion point,leading to considerable reduction in radiographic exposure for both patients and doctors.

OBJECTIVETo explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism.

METHODSAfter being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg), POFS model(70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups(70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase III((KATIII() by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy(TEM).

RESULTSAs compared to control group, exercise score decreased(P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT III( decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1, and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats, while such damage was improved in antagonist group.

CONCLUSIONThe increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Animals ; Fatigue ; Hippocampus ; Humans ; Injections, Intraperitoneal ; Male ; Postoperative Period ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Signal Transduction ; Transaminases

Objective To evaluate the risk factors for carotid atherosclerosis in patients with cerebral infarction.Methods A total of 180 patients with cerebral infarction were divided into no-plaque group (38cases) and plaque group (142 cases) on the results of Color ultrasonography.Plaque group was further divided into stable plaque subgroup (46 patients) and no-stable plaque subgroup (96 patients).Total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),triglyceride (TG),fibrinogen (FIB) and oxidized low density lipoprotein cholesterol (OXLDL) were recorded.The risk factors for carotid atherosclerosis in patients with cerebral infarction were analyzed.Results The percentage of hypertension,diabetes,stroke history,smoking were 88.7％(126/142),43.7％(62/142),53.5％(76/142),50.7％ (72/142) in plaque group and 52.6％(20/38),21.1％(8/38),31.6％(12/38),13.2％(5/38) in no-plaque group.The percentage of hypertension,diabetes,stroke history,smoking in plaque group were higher than those in no-plaque group,and there were significant differences (P ＜ 0.05).The age,TC,LDL-C,OXLDL,FIB were (65 ± 10) years old,(5.3 ±0.8) mmol/L,(3.4 ±0.8) mmol/L,(0.75 ±0.34) mmol/L,(4.8 ± 1.1) g/L in plaque group,and (56 ± 7) years old,(4.6 ± 0.7) mmol/L,(2.8 ± 0.7) mmol/L,(0.45 ± 0.21) mmol/L,(3.8 ± 0.9) g/L in no-plaque group.The age,TC,LDL-C,OXLDL,FIB in plaque group were higher than those in no-plaque group,and there were significant differences (P ＜ 0.05).The percentage of diabetes,stroke history,smoking and LDL-C,OXLDL were 50.0％(48/96),62.5％(60/96),56.2％(54/96),(3.7 ± 0.9) mmol/L,(0.84 ± 0.36)mmol/L in no-stable plaque subgroup,and 30.4％(14/46),34.8％(16/46),39.1％(18/46),(3.1 ± 0.7) mmol/L,(0.60 ± 0.32) mmol/L in stable plaque subgroup.The percentage of diabetes,stroke history,smoking and LDL-C,OXLDL in no-stable plaque subgroup were higher than those in stable plaque subgroup,and there were significant differences (P ＜ 0.05).Multivariate Logistic regression analysis showed that LDL-C (OR =1.724,95％ CI 1.326-2.285),OXLDL (OR =2.464,95％ CI 1.502-5.676) and diabetes (OR =1.484,95％ CI 1.005-1.739) were the independent risk factors for carotid atherosclerosis in patients with cerebral infarction.Conclusion LDL-C,OXLDL and diabetes are the independent risk factors for carotid atherosclerosis in patients with cerebral infarction.

Objective To analyze the influencing factors of having clinical meaningful recanalization (CMR)after revascularization therapy in acute phase of ischemic stroke. Methods A total of 267 consecutive patients with ischemic stroke admitted to the Department of Neurology,Xuanwu Hospital, Capital Medical University and received intravenous thrombolysis or endovascular intervention in acute stage from March 2011 and March 2015 were enrolled retrospectively. CMR was used as a primary endpoint event. They were divided into either a CMR group (n = 92)or a non-CMR group (n = 175)according to whether they had CMR. The baseline data of the patients in both groups were compared by using the Rank sum test and Pearson Chi-Square test. A multivariate logistic regression model was established to analyze the independent influencing factor of CMR. Results The median (interquartile range)age of 267 patents was 60 (51 -69)years,and 69 of them were females (25. 8%);the median (interquartile range)time from onset to treatment was 250 (195 -305)min,and the median (interquartile range)NIHSS score was 10 (6 -15). The baseline NIHSS score,body mass index,blood glucose level,and proportion of diabetes of the CMR group were significantly lower than those of the non-CMR group (all P≤0. 05). The results of multivariate logistic regression analysis showed that the baseline NIHSS (OR,0. 93,95% CI 0. 88 -0. 98;P = 0. 01),intravenous thrombolysis (with respect to endovascular intervention)(OR,0. 35, 95% CI 0. 17 -0. 73;P = 0. 01),and baseline blood glucose (OR,0. 87;95% CI 0. 77 -0. 98;P =0. 02)were the independent negative predictors of CMR. Conclusion The baseline NIHSS,intravenous thrombolysis (with respect to endovascular intervention),and high blood glucose are the negative influencing factors for achieving CMR in the acute phase of ischemic stroke,suggesting blood sugar intervention and endovascular intervention in acute phase may contribute to the improvement of clinical prognosis.

Objective To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. Methods After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg ), POFS model (70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups (70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg ). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase Ⅲ (KATⅢ) by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy (TEM). Results As compared to control group, exercise score decreased (P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT Ⅲ decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1 , and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats , while such damage was improved in antagonist group. Conclusion The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.

Objective To explore the central mechanism of postoperative fatigue syndrome by detecting the expression of NMDA receptor and tryptophan metabolism. Methods After being numbered according to the weight, ninety-six male SD rats were randomly divided into control group (bowel loop was flipped after laparotomy and received intraperitoneal injection of saline at a dose of 1 ml/kg ), POFS model (70% of the length of small intestine was resected and received intraperitoneal injection of saline at a dose of 1 ml/kg), and NMDA antagonist groups (70% of the length of small intestine was resected and received intraperitoneal injection of MK801 at a dose of 1 ml/kg ). Each group was divided into subgroups by postoperative 1, 3, 5 and 7 d, with 8 rats in each subgroup. The hippocampus was removed at each time point after open field test (OFT) to detect the mRNA expression levels of NMDA receptor 1 and kynurenine aminotransferase Ⅲ (KATⅢ) by real-time PCR. Protein level of NMDA receptor 1 was detected by Western blot. High performance liquid chromatography (HPLC) was used to measure the concentrations of tryptophan (TRP), kynurenine (KYN) and kynurenic acid(KYNA). Ultra-structural changes of hippocampal neurons were observed by transmission electron microscopy (TEM). Results As compared to control group, exercise score decreased (P<0.05), rest time and central panel residence time prolonged, periphery/central panel ratio increased (all P<0.05), mRNA and protein expressions of NMDA receptor 1 increased (P<0.05), mRNA expression of KAT Ⅲ decreased (P<0.05), KYN/TRP ratio and KYN/KYNA ratio decreased (all P<0.05) in POFS group on postoperative day 1 and 3. As compared to POFS group, central panel residence time and periphery/central panel ratio decreased on postoperative day 1 , and mRNA and protein expressions of NMDA receptor 1 decreased on postoperative day 1 and 3 (all P<0.05) in antagonist group. TEM revealed that degenerated neuron was found in the hippocampus of POFS rats , while such damage was improved in antagonist group. Conclusion The increased expression level of NMDA receptor may play an important role in POFS. NMDA receptor antagonist MK801 may improve the POFS.