The underlying cause of low response rates to existing immunotherapies is that tumor cells dominate tumor immune escape through surface antigen deficiency and inducing tumor immunosuppressive microenvironment (TIME). Here, we proposed an in situ tumor cell engineering strategy to disrupt tumor immune escape at the root by restoring tumor cell MHC-I/tumor-specific antigen complex (MHC-I/TSA) expression to promote T-cell recognition and by silencing tumor cell CD55 to increase the ICOSL⁺ B-cell proportion and reverse the TIME. A doxorubicin (DOX) and dual-gene plasmid (MAC pDNA, encoding both MHC-I/ASMTNMELM and CD55-shRNA) coloaded drug delivery system (LCPN@ACD) with tumor targeting and charge/size dual-conversion properties was prepared. LCPN@ACD-induced ICD promoted DC maturation and enhanced T-cell activation and infiltration. LCPN@ACD enabled effective expression of MHC-I/TSA on tumor cells, increasing the ability of tumor cell recognition and killing. LCPN@ACD downregulated tumor cell CD55 expression, increased the proportion of ICOSL⁺ B cells and CTLs, and reversed the TIME, thus greatly improving the efficacy of αPD-1 and CAR-T therapies. The application of this in situ tumor cell engineering strategy eliminated the source of tumor immune escape, providing new ideas for solving the challenges of clinical immunotherapy.

OBJECTIVES: To explore the effect of quercetin for mitigating HIV-1 gp120-induced astrocyte neurotoxicity and its underlying mechanism. METHODS: Primary rat astrocytes were isolated and treated with quercetin, HIV-1 gp120, or gradient concentrations of quercetin combined with HIV-1 gp120. The formation of stress granules (SGs) in the treated cells was observed with immunofluorescence assay, and the levels of oxidative stress markers and protein expressions were measured using specific assay kits and Western blotting. HIV-1 gp120 transgenic mice were treated with quercetin (50 mg/kg) by gavage for 4 weeks, and the changes in cognitive functions and oxidative stress levels were examined by behavioral assessments, oxidative stress index analysis in serum, and immunohistochemical and Western blotting of the brain tissue. RESULTS: In primary rat astrocytes, treatment with quercetin significantly reduced HIV-1 gp120-induced SG formation, increased the levels of antioxidant indexes, decreased the levels of oxidative substances, and up-regulated protein level associated with SG depolymerization. In the transgenic mouse models, quercetin obviously improved the cognitive function of the rats, reduced oxidative stress levels, and promoted the expression of proteins associate with SG depolymerization in the brain tissues. CONCLUSIONS Quercetin mitigates HIV-1 gp120-induced astrocyte neurotoxicity and cognitive function impairment by inhibiting oxidative stress, enhancing expressions of SG depolymerization-related proteins, and promoting SG disassembly, suggesting the value of quercetin as a potential therapeutic agent for neuroprotection in HIV-associated neurocognitive disorders.
Animals ; Quercetin/pharmacology* ; Astrocytes/metabolism* ; HIV Envelope Protein gp120 ; Oxidative Stress/drug effects* ; Rats ; Stress Granules/drug effects* ; Mice ; Mice, Transgenic ; Rats, Sprague-Dawley ; Cells, Cultured

AIM:To investigate the effects of γ-synuclein on autophagy and apoptosis of colon cancer cells in-duced by endoplasmic reticulum stress,as well as the protective effect on the cells.METHODS:Gene expression profile chip analysis was performed to compare the cDNA expression profiles between human colon cancer HCT116 cells with γ-synu-clein knockdown and HCT116 cells with control siRNA,and to identify potential molecules related to autophagy and apop-tosis.In colon cancer cell lines,the functional effects of γ-synuclein on autophagy and apoptosis induced by thapsigargin(TG),an endoplasmic reticulum stress-inducing agent,were systematically explored by conducting immunofluorescence staining,Western blot,CCK-8 assay,flow cytometry,and transmission electron microscopy.Western blot was used to de-tect the expression of γ-synuclein protein,autophagy-related proteins[microtubule-associated protein 1 light chain 3(LC3),beclin-1,autophagy-related protein 5(ATG5)and ATG7],and apoptosis-related proteins[poly(ADP-ribose)polymerase(PARP),pro-caspase-3,and pro-caspase-9].To further analyze the mechanism of γ-synuclein in regulating autophagy and apoptosis,extracellular signal-regulated kinase(ERK)inhibitor PD98059,ERK inhibitor SP600125 and c-Jun N-terminal kinase(JNK)activator anisomycin were applied separately to test HCT116 cells transfected with γ-synu-clein siRNA.Subsequently,autophagy proteins,apoptosis proteins,and ERK and JNK pathway-related proteins were de-tected by Western blot.RESULTS:The TG-induced autophagy of colon cancer cells mainly occurred at the early stage(0～24 h),and apoptosis mainly occurred at the late stage(36～48 h).Endoplasmic reticulum stress up-regulated the ex-pression of γ-synuclein in colon cancer cells,which was associated with enhanced autophagy.γ-Synuclein promoted au-tophagy by activating ERK and JNK pathways at the early stage(0～24 h),and inhibited apoptosis by blocking JNK path-ways at the late stage(24～48 h)to protect HCT116 cells.In our model,γ-synuclein was observed to play a critical role in the transition from endoplasmic reticulum stress-induced autophagy to apoptosis.CONCLUSION:In the context of endo-plasmic reticulum stress,γ-synuclein promotes autophagy and inhibits apoptosis by regulating ERK and JNK signaling pathways,thus protecting colon cancer cells.This provides a potential idea for anti-tumor therapy.

Based on the four major classic studies of perioperative treatment of locally advanced gastric cancer (LAGC), the North American Intergroup-0116 trial, the European MRC MAGIC trial, the Japan ACTS-GC trial and Korea-China CLASSIC trial, the perioperative therapy of LAGC was divided into three major patterns in the world, namely, postoperative adjuvant chemoradiotherapy in the North America, perioperative chemotherapy in the Europe and postoperative adjuvant chemotherapy in the East Asia. In recent years, scholars around the world have done many researches on the perioperative treatment of gastric cancer. For instance the German FLOT4-AIO trial pushed the perioperative chemotherapy of gastric cancer to a high point, so the NCCN guide changed perioperative chemotherapy to the preferred recommendation, and rewrote the perioperative chemotherapy regimen. The ARTIST trial in Korea showed that the addition of radiotherapy to the adjuvant chemotherapy after D2 radical resection of gastric cancer could not improve the overall survival rate, and further defined adjuvant chemotherapy as the standard treatment in D2 resection of gastric cancer. Asian scholars are actively exploring the application of perioperative chemotherapy in LAGC. For Bulky N cases, neoadjuvant chemotherapy has been recommended as the standard treatment in the Japanese guidelines. The JOCG1509,the RESOLVE and other studies will provide more effective evidence-based recommendations for the best perioperative therapy options of LAGC in Asian countries. At present, it is not clear whether perioperative chemotherapy or postoperative adjuvant chemotherapy is better. In this article, the development course of the three patterns of perioperative therapy of gastric cancer, the research progress in the perioperative period of gastric cancer in recent years, and the changes of guidelines are reviewed in order to provide reference for clinical practice.
Combined Modality Therapy ; history ; methods ; Gastrectomy ; History, 20th Century ; History, 21st Century ; Humans ; Perioperative Care ; history ; methods ; Stomach Neoplasms ; history ; pathology ; surgery ; therapy

Objective To explore the efficacy of middle and high (mid-high) flow intracranial-external vascular bypass in treatment of complex intracranial aneurysms and selection of grafts. Methods The clinical data of 79 patients with complicated intracranial aneurysms treated by mid-high flow extracranial-intracranial bypass in our hospital from August 2010 to October 2017 were collected retrospectively. The grafts were radial artery (n=21), saphenous vein of the calf segment (n=29) or thigh saphenous vein segment (n=29). The efficacy was determined based on Glasgow outcome scale (GOS) scores at discharge and modified Rankin scale (mRS) scores at follow-up, and the differences of occlusion in different types of grafts were analyzed. Results CTA showed patency of the grafts in all patients one d after surgery. There were 6 patients having vascular occlusion: 2 patients (the grafts at saphenous vein of the calf segment ) were occluded 3 and 4 d after surgery, without symptom; 2 patients (the grafts at the radial artery), with decreased limb muscle strength, were occluded 5 and 25 d after procedure; 2 patients ( the grafts at the saphenous veins of the calf segment) were occluded 6 months after procedure without any symptom. There were 4 patients developed cerebral ischemia after operation: one had cerebral infarction and three had vasospasm. GOS scores at discharge and mRS scores at follow-up showed that 78 patients had improved symptoms and good prognosis; one patient showed no improvement in symptoms and plant survival. Conclusion Mid-high flow extracranial-intracranial bypass for treatment of complex intracranial aneurysms is effective; the graft should be individually selected based on preoperative assessment results.

Pseudomyxoma peritonei syndrome (PMP) is characterized by a gradual expansion of mucoid tumour and fluid at specific sites within abdominopelvic regions as a result of a perforated appendiceal adenoma. The standard therapy for PMP is combining cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy. Maximal tumor debulking surgery (MTD) may be beneficial in patients in whom complete cytoreductive surgery (CCRS) cannot be achieved. It is now recognized that CCRS is one of the strongest predictors of long term survival in patients with PMP. The 5-year survival rate in patients who underwent CCRS was 80.0 %-87.4 %, however the rate in patients who underwent MTD was only 24.0 %-39.2 %.This article reviews the pathological classification,diagnosis and treatment of PMP.

Objective To evaluate the actual effect of the schistosomiasis control program in Jiangsu Province from 2010 to 2015. Methods A total of 67 schistosomiasis-endemic counties in 10 cities were selected, and a combination of retrospective investigation and on-site investigation was adopted to collect and record the epidemic data of the counties from 2010 to 2015, and a retrospective survey database of epidemic situation was established. The effects of integrated control strategies with both Oncomelania hupensis snail control and infection source control were evaluated. Results From 2010 to 2015, 2 465 911 persons who lived in endemic areas were detected for schistosomiasis, with 16 974 positive cases of blood examinations, and 8 positive cases of fecal examinations. Totally 5 145 people with advanced schistosomiasis were treated and 40 460 people with the history of schistosome cercarial-infested water contact received the expanded chemotherapy. A total of 127 636 cattle raised in the endemic areas were detected, and 51 619 cattle (head-times) with the history of cercarial-infested water contact also received the expanded chemotherapy. The area with snails control by molluscicides was 18 604.84 hm². By the end of 2015, schistosomeinfected snails had not been found and there was no zoological schistosome infection for 5 consecutive years, and in addition, there had been no acute schistosome-infected persons for 6 consecutive years in the whole province. The area with snails dropped to 1 977.18 hm², with a decreasing rate of 55.24% compared with that in 2010. Conclusion After the implementation of the plan for the prevention and control of schistosomiasis in Jiangsu Province (2010–2015), the prevention and control of schistosomiasis has achieved remarkable effects and realized the goal of the plan.

Objective To study the relationship between intrauterine infection and early neonatal sepsis.Method From October 2015 to September 2016,the clinical data of pregnant mothers and their newborns in Shenzhen Longhua District Central Hospital were collected,and data of Shenzhen People's Hospital from January 2016 to June 2016 were collected.100 pairs of pregnant mothers and their newborns with confirmed or suspected intrauterine infection were selected as the observation group,and another 100 pairs without intrauterine infection during the same period as the control group.The ratio of term infants vs.premature infants was 1∶ 1.The complete blood count (CBC),CD64,procalcitonin (PCT) and C-reactive protein (CRP) were measured in peripheral blood of all mothers on the day of delivery.The CBC,CD64,CRP,PCT,blood culture of both umbilical venous blood and peripheral blood in neonates were examined and the pathological examination of placenta was performed.Result The positive rate of placental pathology and umbilical cord blood culture in observation group were significantly higher than that in the control and the positive rate in preterms was higher than the terms in observation group (P ＜ 0.05).No significant differences existed between term and premature newborns on the positive rate of peripheral blood culture (P ＞ 0.05).The positive rate of blood culture from umbilical cord blood was higher than peripheral blood in observation group (P ＜ 0.05),but no significant difference in control group (P ＞ 0.05).The incidence of septicemia in term and premature newborns in observation group was significantly higher than the control group (P＜ 0.05).The CD64,PCT in mother's peripheral blood and umbilical cord blood,and CRP in mother's blood were all higher than the control group,the differences were statistically significant (P ＜ 0.05),but CRP in umbilical cord blood in both group were similar (P ＞ 0.05).The area under ROC curve of CD64 and PCT in mother's peripheral blood,CD64 and PCT in umbilical cord blood to diagnose early-onset septicemia in newborns was 0.755,0.793,0.852 and 0.811,respectively.Conclusion The risk of neonatal infections is significantly increased because of intrauterine infection.Combination of peripheral and umbilical blood cultures can increase the accuracy of sepsis diagnosis.Both CD64 and PCT in umbilical cord blood and maternal blood can be used as indicators of intrauterine infection with a predictive value in the diagnosis of early-onset neonatal sepsis.

Objective To understand the status of service contract signing conducted by primary medical and health institutions.Methods A questionnaire survey and in-depth interview methods were used to study the service contract signing at primary health care institutions.Results The contract signing rate of the institutions surveyed was 1 9.1%,and valid contract signing rate was 76%.Senior people above 65 years old accounted for 33.5% of those signers,while hypertension patients accounted for 1 9.5% and diabetes patients for 10.6%.Interviews to the general practitioners team at the primary health institutions found that main factors affecting residents′ intention to sign were drug availability, attraction for signing the services,treatment habits among others.Interviews to the staff the primary health institutions found that contracted services are facing such difficulties as medical staff shortage,lack of motivation,lack of competence among others.Interviews to leaders of the primary health institutions found that the lack of publicity and support of medical insurance also has great influence to service contract signing.Conclusions The enthusiasm of general practitioners and residents to sign up for the service remains to be improved.

Objective:To investigate the effects of sign-contract services on hypertension patient disease control and the satisfaction of medical staff. Methods:a face-to-face questionnaire survey was conducted among hypertension patients selected from 20 primary health centers in 10 provinces in China. Results:This paper collected 1 ,881 valid questionnaires, and the average age of the population was 65. 72 ± 10. 88. Respondents that received sign-contract services accounted for 53. 88%, and there was no difference between patients who signed the service contract and who did not in terms of demographics. In self-reporting of blood pressure controls, respondents who signed the service contract, aged 40~50 years old, enjoyed the free medical care, preferred to seek medical services from primary a-gencies ( i. e. community health centers and township hospitals) for minor illnesses, controlled their blood pressure better ( P<0. 05 ) . Respondents enjoyed the civil resident medical insurance, preferred to seek medical care from community health centers for minor illnesses and signed the service contract were more likely to be satisfied with their medical practitioner (P<0. 05). After adjusting for age, gender, education level, medical insurance style, patient willingness to seek medical care for minor illnesses, signing service contracts was found to be an independent factor both associated with blood pressure self-control and attitudes towards medical service providers, with the odds ratio of 3. 007 (95%CI:2. 572 -3. 517) and 1. 814 (95%CI: 1. 563 -2. 105) respectively. Conclusion: Contracts are correlated with blood pressure control and satisfaction toward medical practitioners, which means that patients who signed the service contract control their blood pressure better and are more satisfied with their medical deliverers.