Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macro-phages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative acti-vation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Objective:To investigate the correlation between serum cystatin C (CysC) and clinical and pathological features of IgA nephropathy.Methods:Four hundred and twenty-one cases of primary IgA nephropathy diagnosed by renal biopsy in Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from January 2010 to January 2021 were retrospectively analyzed. According to the serum CysC level at the time of renal biopsy, the patients were divided into high serum CysC group and normal serum CysC group, and the clinical data and pathological indices of the patients were compared. Spearman correlation analysis was used to analyze the correlation between estimated glomerular filtration rate (eGFR) and serum CysC. The clinicopathological factors related to the serum CysC level were analyzed by multiple linear regression. The area under the receiver operator characteristic curve (AUC) was used to evaluate the ability of serum CysC level to predict related pathological injury.Results:The age, prevalence of hypertension, serum creatinine, urea and uric acid levels of high serum CysC group were significantly higher than those of normal serum CysC group, while the eGFR level was significantly lower than that of normal serum CysC group ( P<0.05). Spearman correlation analysis showed that serum CysC was negatively correlated with eGFR ( r=-0.744, P<0.001). In terms of pathological injury, the degree of renal tubular atrophy and renal interstitial fibrosis (T) and renal arteriole wall thickening (A) in high serum CysC group were more serious than those in normal serum CysC group ( P<0.05). Multiple linear regression analysis showed that the prevalence of hypertension, serum creatinine, urea, uric acid, T and A were correlated with serum CysC levels (standard regression coefficient β=0.048, 0.299, 0.260, 0.134, 0.195, 0.068, respectively, P<0.05). After adding serum CysC on the basis of clinical features, the prediction efficiency of renal tubular atrophy and renal interstitial fibrosis was higher (AUC were 0.829 [95% CI 0.787-0.870], 0.847 [95% CI 0.808-0.886], P<0.05). Conclusions:Patients with older age, hypertension, poor renal function and severe pathological damage are more likely to have elevated serum CysC levels. Serum CysC was related to the prevalence of hypertension, creatinine, urea, uric acid, T and A. Combined with serum CysC level can effectively improve the ability prediction of T.

Objective:To investigate the anatomy and therapeutic effecton skin soft tissue defect at the great toe of perforator flap from distal deep branch of medial plantar artery.Methods:The arteries of one adult foot specimens were filled with red latex and vascular anatomy was performed. Branch distribution and anastomosis of medial plantar artery and dorsal foot artery were observed. The clinical data of 12 patients with skin soft tissue defect at the great toe repaired by retrograde perforator flap from distal deepbranch of medial plantar artery from September 2016 to September 2019 in Affiliated Hospital of Zunyi Medical University was selected, and the donor sites were repaired with skin grafts. The flap survival and complications were observed.Results:Anatomy result demonstrated that deep branch of the medial plantar artery was direct continuation of the medial plantar artery. It traveled along between short toe flexor muscle and abductor hallucis muscle, and gave out several perforators. The proximal perforators passed through the abductor hallucis muscle, and anastomosed with superficial branch of medial plantar artery, anterior medial malleolus artery, and medial tarsal artery. Three perforators were issued at the proximal end of the first metatarsophalangeal joint, namely articular perforator, cutaneous perforator, and communication branch. The cutaneous perforator was main blood supply source for perforator flap from distal deep branch of medial plantar artery.A total of 12 skin flaps were harvested from 12 patients, with an area from 4.5 cm×3.0 cm to 9.0 cm×6.0 cm. Postsurgery dark purple and a few blisters occurred in three flaps, and the sutures at the pedicle were immediately removed, and the flap was coated with antibiotic ointment to keep it moist, then the flap color gradually improved after postsurgery 5 days.12 skin flaps eventually survived completely. All patients were followed up by telephone for 2-12 months. The flap color, texture and appearance were excellent. The traumatic feet walked normally.Conclusions:The perforator flap from distal deep branch of medial plantar artery has reliable blood supply for retrograde repairing small and medium skin defect at the great toe of distal the first metatarsophalangeal joint, with simple operation, less trauma, and positive postoperative effect.

Objective:To investigate the anatomy and therapeutic effecton skin soft tissue defect at the great toe of perforator flap from distal deep branch of medial plantar artery.Methods:The arteries of one adult foot specimens were filled with red latex and vascular anatomy was performed. Branch distribution and anastomosis of medial plantar artery and dorsal foot artery were observed. The clinical data of 12 patients with skin soft tissue defect at the great toe repaired by retrograde perforator flap from distal deepbranch of medial plantar artery from September 2016 to September 2019 in Affiliated Hospital of Zunyi Medical University was selected, and the donor sites were repaired with skin grafts. The flap survival and complications were observed.Results:Anatomy result demonstrated that deep branch of the medial plantar artery was direct continuation of the medial plantar artery. It traveled along between short toe flexor muscle and abductor hallucis muscle, and gave out several perforators. The proximal perforators passed through the abductor hallucis muscle, and anastomosed with superficial branch of medial plantar artery, anterior medial malleolus artery, and medial tarsal artery. Three perforators were issued at the proximal end of the first metatarsophalangeal joint, namely articular perforator, cutaneous perforator, and communication branch. The cutaneous perforator was main blood supply source for perforator flap from distal deep branch of medial plantar artery.A total of 12 skin flaps were harvested from 12 patients, with an area from 4.5 cm×3.0 cm to 9.0 cm×6.0 cm. Postsurgery dark purple and a few blisters occurred in three flaps, and the sutures at the pedicle were immediately removed, and the flap was coated with antibiotic ointment to keep it moist, then the flap color gradually improved after postsurgery 5 days.12 skin flaps eventually survived completely. All patients were followed up by telephone for 2-12 months. The flap color, texture and appearance were excellent. The traumatic feet walked normally.Conclusions:The perforator flap from distal deep branch of medial plantar artery has reliable blood supply for retrograde repairing small and medium skin defect at the great toe of distal the first metatarsophalangeal joint, with simple operation, less trauma, and positive postoperative effect.

OBJECTIVETo study the risk factor of perioperative complication in gastric cancer patients with radical therapy and its influence on prognosis.

METHODSClinical, pathological and follow-up data of 1 148 gastric cancer patients undergoing radical gastrectomy at Tianjin Medical University Affiliated Tumor Hospital between January 2009 and August 2011 were retrospectively collected. Pearson 2 test and Logistic regression analysis were used to analyze the risk factor of perioperative complication. Cox regression analysis was used to evaluate the influence of perioperative complications on the prognosis in patients after radical gastrectomy. Kaplan-Meier survival curve was applied to calculate the survival.

RESULTSOf 1 148 patients, 851 were male, 297 were female, age ranged from 19 to 89 (average 59.9) years. Perioperative complication occurred in 312 cases (27.2%), including 140 cases of pulmonary infection and 53 cases of abdominal infection. Multivariate Logistic regression analysis showed that ≥65 years old (OR:0.736, 95%CI: 0.558 to 0.971, P=0.030), serum albumin less than 35 g/L(OR:2.626, 95%CI: 1.479 to 4.665, P=0.001), Borrmann type IIII((OR: 0.748, 95%CI: 0.610 to 0.917, P=0.005), tumor site at upper 1/3 of stomach (OR:1.326, 95%CI:1.167 to 1.506, P=0.000), combined organ resection(OR:0.624, 95%CI:0.428 to 0.909, P=0.014) were independent risk factors of perioperative complication. Tumor site at upper 1/3 of stomach (OR:1.649, 95%CI: 1.368 to 1.988, P=0.000), ≥65 years old (OR:0.548, 95%CI:0.379 to 0.792, P=0.001), without intraoperative chemotherapy (OR:1.671, 95%CI:1.146 to 2.437, P=0.008) were independent risk factors of perioperative pulmonary infection; Borrmann type IIII((OR:0.576, 95%CI:0.369 to 0.900, P=0.015), with intraoperative chemotherapy (OR:0.431, 95%CI:0.230 to 0.810, P=0.009), intraoperative blood loss ≥400 ml(OR:0.411, 95%CI:0.176 to 0.959, P=0.040) and combined organ resection (OR:0.412, 95%CI:0.215 to 0.789, P=0.008) were independent risk factors of perioperative intraperitoneal infection. Cox regression analysis revealed that without intraoperative chemotherapy, proximal subtotal or total gastrectomy, TNM stage III(, N3 stage lymph node metastasis, positive soft tissue outside lymph node, combined organ resection and organ failure were independent risk factors affecting the prognosis of gastric cancer patients after radical resection (all P<0.05), however the perioperative complication was not independent risk factor affecting the prognosis (P=0.259). The median survival time was 35 months, and 5-year survival rate was around 38.7%. The median survival time of gastric cancer patients with operative complications and without complications were 28.0 and 36.5 months, and the 5-year survival rates were 37.2% and 39.3%, whose difference was not statistically significant (P=0.259).

CONCLUSIONThere is a higher risk of perioperative complication in those gastric cancer patients with old age, preoperative low serum albumin level, tumor site at upper 1/3 of stomach, Borrmann type IIII(, intraoperative combined organ resection, while the perioperative complication has no significant effects on the long-term survival.

Objective To investigate clinicopathological features of pancreatic carcinoma with or without lymph node metastasis,and to explore the relationship between the lymph node metastasis and the prognosis of pancreatic carcinoma.Methods The clinical and follow up data of 216 patients with pancreatic carcinoma from 2001 to 2015 were retrospectively analyzed.Kaplan-Meier method was used to estimate survival rates and plot survival curves.Results The postoperative survival time was 4-86 months,the median survival time was 19 months,and the postoperative 1,3 and 5 year survival rates were 65.1％,33.8％,20.5％,respectively.Patients with positive lymph node metastasis were with 1,3,5 year survival rates of 36.5％,12.2％,0％,those with no lymph node metastasis were with 1,3,5 year survival rates of 70.3％,38.0％,21.4％ (x2 =15.803,P ＜ 0.001).Conclusions Lymph node metastasis in patients with pancreatic cancer is worse than that without lymph node metastasis.Lymph node metastasis is one of the main prognostic factors in patients after radical resection of the pancreatic cancer.

Objective: To evaluate the efficacy and safety of maintenance therapy with reduced dose of rhTPO in the patients with primary immune thrombocytopenia (ITP) who attained stable platelet (PLT) counts after daily administration of rhTPO. Methods: Treatment was started with a daily administration of rhTPO (300 U/kg) for 2 consecutive weeks. Patients who attained stable PLT≥50×10⁹/L were enrolled to maintenance therapy starting with every other day administration of rhTPO, then adjusted dose interval to maintain platelet count (30-100) ×10⁹/L. Results: A total of 91 eligible patients were enrolled. Fourteen patients discontinued the study due to noncompliance (12/14) and investigator decision (2/14) . Among 77 patients who completed the study, 38 patients with the administration of rhTPO at every other day or less could maintain PLT≥30×10⁹/L for 12 weeks. The percentage of patients with a platelet response (PLT≥30×10⁹/L) at 4^th week, 8^th week and 12^th week of maintain therapy was 92.6% (63/68) , 82.7% (43/52) and 85.0% (34/40) , respectively. Median platelet counts remained in the range of (70-124) ×10⁹/L. The overall incidence of rhTPO-related adverse events was 7.7%. All the adverse events were generally mild. Conclusion Extending the dose interval of rhTPO is feasible to maintain stable platelet count in the patients with ITP, but the optimal dose interval is uncertain and might vary with individuals.

Objective To analyze the correlation between the status of the donation after brain and cardiac death (DBCD)donors and postoperative recovery of the organ function in the liver and renal transplant recipients.Methods The assessment data and organ protection measures of 12 DBCD donors admitted to the Organ Transplantation Center in Sichuan Provincial People’s Hospital from August 2011 to November 2013 were retrospectively analyzed.The parameters of postoperative recovery of 12 liver and 22 renal transplant recipients were also assessed.The correlation between the parameters of the donors and postoperative recovery of the liver and renal transplant recipients was statistically analyzed.Results Among 12 liver transplant recipients,1 patient had primary non-function (PNF)(1 /12,8%)and 11 cases developed delayed graft function (DGF) after renal transplantation (11 /22,50%).Intensive care unit (ICU)period,liver function,maintaining systolic blood pressure (SBP),blood coagulation function,blood glucose level and electrolyte (Na +/K +) were significantly correlated with postoperative recovery of the liver and kidney function in the recipients (all in P <0.05 ).Age,cause of brain death,maintaining diastolic blood pressure (DBP),activated partial thromboplastin time (APTT)and pH of arterial blood gas (ABG)were associated with postoperative recovery of the liver function.Total bilirubin and white blood cell count (WBC)were correlated with postoperative recovery of kidney function.Conclusions DBCD donors cater to the specific conditions in China.The incidence of postoperative PNF in liver recipients is relatively low whereas and the incidence of DGF after renal transplantation is relatively high.Assessment of the DBCD donors and organ protection measures should be specifically taken to enhance the clinical efficacy of liver and renal transplantation from DBCD donors.

Objective:AFM1-BSA and AFM1-OVA were synthesized and then identified in this experiment.Methods: Using oximation method ,AFM1 was transformed to oxime compounds while the reaction process was monitored via TLC method aiming to identify the compounds.Coupled with carrier protein BSA and OVA respectively , we obtained AFM1-BSA and AFM1-OVA, then identified synthetic antigen via UV spectrophotometry and SDS-PAGE.Antigens were injected into experimental animals , finally obtaining the murine multi-antiserum.Eventually , the multi-antiserums were detected via indirect inhibition ELISA method to judge whether the antigens were effectively or not.Results:After oximation reaction ,the migration distance of oxime compounds in the thin layer plate was shorter.The maximum absorption peak of AFM1-BSA occurred in 274 nm,and was inconsistent with both UV absorption peaks of BSA and AFM 1.The electrophoretic velocity of AFM 1-BSA was less than that of BSA.All the titers of three immunized mice were 1×10-4 approximately;the multi-antiserum from No.3 sample had the best sensitivity ,its IC50 was 359.9 ng/ml.Conclusion:In this study,we obtained AFM1 artificial antigen and murine multi-antiserum of high sensitivity.

Objective To evaluate the effects of asymptomatic arteriovenous fistula closure on left ventricular morphology and function in renal transplant recipients.Methods Between March 2007 and March 2011,a total of 60 patients undergoing consecutive kidney transplantation with asymptomatic arteriovenous fistula were divided randomly into two groups: arteriovenous fistula closure group,and non-arteriovenous fistula closure group.By using echocardiography,the changes in CO,CI,EF,LVEDV and LVMI were analyzed.Results At 12th month after transplantation,the values of CO,LVEDV and LVMI were significantly lower than those before transplantation (P＜0.05).The value of CI also showed a tendency to decrease (P＞0.05),and the value of EF was increased significantly (P＜0.05).At 6th month after arteriovenous fistula closure (18 months after transplantation),the values of CO,CI,LVEDV and LVMI were significantly lower than those before arteriovenous fistula closure (12 months after transplantation) (P＜0.05),and the value of EF was increased significantly (P＜0.05),but the values of CO,CI,EF,LVEDV and LVMI remained unc(b)anged in controls (P＞0.05).At 18th month after transplantation,the values of CO (4.4 ±0.8 L/min),CI [3.0 ± 0.8 L·min-1·m-2],LVEDV (110.0 ± 17.4 ml) and LVMI (114.7 ± 42.5g/m2) in trial group were significantly lower than the values [CO: 5.1 ± 0.9 L/min,CI: 3.5 ± 1.0L·min-1·m-2,LVEDV: 121.4±19.3 mL,LVMI: 138.4±44.1 g/m2] in controls (P＜0.05),and the value of EF (75.2％ ± 7.4％ vs.70.5％ ± 8.2％) significantly higher (P＜005).Conclusion In both groups,kidney transplantation benefits significantly the regression of cardiac mass,cardiac index and left ventricular dimensions,but closure of asymptomatic AVF induces more significant regression.