Recent clinical studies have shown that mutation of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) gene in cancer cells may be associated with immunosuppressive tumor microenvironment (TME) and poor response to immune checkpoint blockade (ICB) therapy. Therefore, efficiently restoring PTEN gene expression in cancer cells is critical to improving the responding rate to ICB therapy. Here, we screened an adeno-associated virus (AAV) capsid for efficient PTEN gene delivery into B16F10 tumor cells. We demonstrated that intratumorally injected AAV6-PTEN successfully restored the tumor cell PTEN gene expression and effectively inhibited tumor progression by inducing tumor cell immunogenic cell death (ICD) and increasing immune cell infiltration. Moreover, we developed an anti-PD-1 loaded phospholipid-based phase separation gel (PPSG), which formed an in situ depot and sustainably release anti-PD-1 drugs within 42 days in vivo. In order to effectively inhibit the recurrence of melanoma, we further applied a triple therapy based on AAV6-PTEN, PPSG^@anti-PD-1 and CpG, and showed that this triple therapy strategy enhanced the synergistic antitumor immune effect and also induced robust immune memory, which completely rejected tumor recurrence. We anticipate that this triple therapy could be used as a new tumor combination therapy with stronger immune activation capacity and tumor inhibition efficacy.

ObjectiveA previous multicenter， single-arm phase Ⅱ clinical study evaluated the efficacy and safety of the PD-1 inhibitor camrelizumab in combination with the antiangiogenic drug apatinib in patients with recurrent/metastatic cervical cancer. In the current study， we aimed to report the patient-reported outcomes （PRO） in patients with advanced cervical cancer. MethodsThe researchers filled out quality of life questionnaire FACT-Cx with the patients face-to-face at the baseline and every two treatment cycles. The patients provided the questionnaire until disease progression. For patients who continued the study， the data cutoff date for the questionnaire was Oct12， 2020. ResultsIn this study， 41 patients who received treatment finished at least one FACT-Cx questionnaire. The scores of FACT-Cx questionnaire at baseline， the first 6 cycles， and after 6 cycles of treatment （range， 7-15cycle） were 114.53±18.23， 124.08±15.23 and 132.82±21.97， respectively. The scores of questionnaire at the first 6 cycle and after 6 cycles of treatment were significantly increased when compared with those at baseline （P＜0.05）. With respect to each dimension of the FACT-Cx questionnaire， physical status （such as mental state， limb pain）， emotional status （such as sadness， tension）， functional status （such as daily activities） and additional concerns （such as sexual function）， the average scores of these dimensions was significantly higher after 6 treatment cycles than those at baseline （P<0.05）. Social/family status dimensions （such as family relationships） did not change significantly. In the first 6 cycles， the incidence of grade 3 to 4 adverse events （AEs） was 71.11%. However， the incidence of grade 3 to 4 AEs decreased significantly to 25.0% after 6 treatment cycles， with the frequencies of hypertension and fatigue decreasing significantly. ConclusionsCamrelizumab combined with apatinib significantly improves the overall quality of life of patients with recurrent/metastatic cervical cancer. The scores of FACT-Cx questionnaire in multiple dimensions， such as physiological status， emotional status， functional status， and the additional status were significantly increased. Moreover， the questionnaire scores still increase after 6 treatment cycles compared with those of the first 6 cycles， indicating that the improvement of quality of life is durable.

Background::Previous studies have shown that inflammation plays an important role in intracranial atherosclerotic stenosis (ICAS). The platelet-to-lymphocyte ratio (PLR) has recently emerged as a potential inflammatory biomarker. This study aimed to explore the association of the PLR with ICAS in a Chinese Han population.Methods::A total of 2134 participants (518 with ICAS, 1616 without ICAS) were enrolled in this study. ICAS was defined as atherosclerotic stenosis >50% or the occlusion of several main intracranial arteries. Multivariable logistic regression analyses were used to assess the association of the PLR with ICAS. Additional subgroup analyses were performed according to age (<60 vs. ≥ 60 years) and acute ischemic stroke. Results::Multivariate regression analysis showed that a high PLR was associated with a higher risk of ICAS in all participants ( P < 0.001). Compared with the lowest quartile, the fourth PLR quartile was significantly associated with ICAS (OR 1.705, 95% confidence interval 1.278–2.275, P < 0.001). In the subgroups stratified by age, an association between the PLR and ICAS was found in the late-life group ( P < 0.001), but not in the mid-life group ( P = 0.650). In the subgroups stratified by acute ischemic stroke, the relationship between an elevated PLR and a higher risk of ICAS remained unchanged (stroke group, P < 0.001; non-stroke group, P = 0.027). Conclusions::An elevated PLR was associated with a higher risk of ICAS in a Chinese Han population. The PLR might serve as a potential biomarker for ICAS in the elderly population.

Arm ; Asian Continental Ancestry Group ; Bias (Epidemiology) ; Carboplatin ; Disease-Free Survival ; Doxorubicin ; Drug Therapy ; Follow-Up Studies ; Humans ; Maintenance Chemotherapy ; Ovarian Neoplasms ; Prognosis ; Quality of Life ; Recombination, Genetic ; Sample Size

Objectives: An Asian Gynecologic Oncology Group phase III randomized trial was conducted to determine whether maintenance chemotherapy could improve progression-free survival (PFS) in stages III/IV ovarian cancer. Methods: Between 2007 and 2014, 45 newly-diagnosed ovarian cancer patients were enrolled after complete remission and randomized (1:1) to arm A (4-weekly carboplatin area under the curve 4 and pegylated liposomal doxorubicin [PLD] 30 mg/m2, n=24) for 6 cycles or arm B (observation, n=21). The primary end-point was PFS. A post hoc translational study was conducted to deep sequence BRCA/homologous recombination deficiency (HRD) genes, because BRCA/HRD mutations (BRCA/HRDm) are known to be associated with better prognosis. Results: Enrollment was slow, accrual was closed when 7+ years had passed. With a medianfollow-up of 88.9 months, the median PFS was significantly better in arm A (55.5 months) than arm B (9.2 months) (hazard ratio [HR]=0.40; 95% confidence interval [CI]=0.19–0.87; p=0.020), yet the median overall survival was not significantly different in arm A (not reached) than arm B (95.1 months) (p=0.148). Overall grade 3/4 adverse events were more frequent in arm A than arm B (60.9% vs 0.0%) (p<0.001). Quality of life was generally not significantly different. Distribution of BRCA1/2m or BRCA/HRDm was not significantly biased between the two arms. Wild-type BRCAon-HRD subgroup seemed to fare better with maintenance therapy (HR=0.35; 95% CI=0.11–1.18; p=0.091). Conclusions Despite limitations in small sample size, it suggests that maintenance carboplatin-PLD chemotherapy could improve PFS in advanced ovarian cancer.

AIM:To investigate the effect of 27nt-microRNA (27nt-miRNA) on the expression of smooth muscle 22α protein (SM22α) and the cell viability, migration and phenotypic changes of vascular smooth muscle cells (VSMCs).METHODS:The highly expression plasmids of 27nt-miRNA, and anti-27nt-miRNA and negative control plasmids were constructed, packaged with lentivirus and transfected into the rat primary VSMCs.Platelet-derived growth factor BB (PDGF-BB) was added to induce VSMCs phenotype conversion.The cell viability was measured by MTT assay.The migration ability was detected by scratch assay.The mRNA and protein expression of SM22αwas determined by RT-PCR, immunocytochemical staining and Western blot.RESULTS:Compared with normal group, the cell viability in PDGF-BB group was increased (P<0.05) , the migration ability was increased (P<0.05) and the expression of SM22αat mRNA and protein level was decreased (P<0.05).Compared with negative control lentiviral group, the cell viability in 27ntmiRNA over-expression group was decreased (P<0.05) , the migration ability was decreased (P<0.05) , and the mRNA and protein expression of SM22αwas increased (P<0.05).While in anti-27nt-miRNA group, the cell viability was increased (P<0.05) , the migration ability was increased (P<0.05) , and the mRNA and protein expression of SM22αwas decreased (P<0.05).CONCLUSION:27nt-miRNA significantly increases the expression of SM22α, while inhibits the viability and migration ability of VSMCs, and inhibits its phenotypic shift from contractile to synthetic.

OBJECTIVE: To test the hypothesis that the inhibition of endoplasmic reticulum (ER) stress-induced apoptosis in oxidized low-density lipoproteins (ox-LDL)-induced human aortic-vascular smooth muscle cells (HA-VSMCs) was associated with suppression of the protein kinase RNA-like ER kinase (PERK)-eukaryotic translation initiation factor 2α (eIF2α)-activating transcription factor 4 (ATF4)-CCAAT/enhancer binding protein homologous protein (CHOP) signaling pathway by Pollen Typhae total flavone (PTF). METHODS: Primary HA-VSMCs were cultured and identified. The cultured HA-VSMCs were randomized into 5 groups, including a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an HPTF group (70 μg/mL high ox-LDL+500 μg/mL PTF), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), and a LPTF group (70 μg/mL high ox-LDL+100 μg/mL PTF) in the first part; and a normal control group, an ox-LDL group (70 μg/mL high ox-LDL), an MPTF group (70 μg/mL high ox-LDL+250 μg/mL PTF), a shRNA group (transducted with PERK shRNA lentiviral particles), a scramble shRNA group (transducted with control shRNA lentiviral particles), an MPTF+ox-LDL+shRNA group (250 μg/mL PTF+70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) and an ox-LDL+shRNA group (70 μg/mL high ox-LDL+PERK shRNA lentiviral particles) in the second part. The protein expression levels of ER-associated apoptosis proteins were detected by Western blot, and their mRNA expression levels were detected by quantitative real-time reverse transcription-polymerase chain reaction. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was applied to test cell viability, and the level of apoptosis was monitored by flow cytometry. RESULTS: The MTT assay and flow cytometry showed that the ox-LDL group had a significant increase in apoptosis, which was attenuated in PTF treatment groups and shRNA groups. Moreover, the ox-LDL group had increased protein and mRNA levels of binding immunoglobulin protein and ER-associated apoptosis proteins, such as PERK, eIF2α, ATF4 and CHOP, which were attenuated in PTF treatment groups and shRNA groups. CONCLUSIONS The apoptosis induced by ox-LDL had a strong relation to ER stress. The protective effect of PTF on ER stressinduced apoptosis was associated with inhibition of the PERK-eIF2α-ATF4-CHOP pathway, which might be a potential therapeutic strategy for enhancing the stability of atherosclerotic plaques.

Objective To analyze the clinical features and risk factors of cirrhotic patients complicated with infections. Methods The clinical and laboratory characteristics of cirrhotic patients complicated with infections hospitalized from April 2014 to June 2017 were retrospectively analyzed. Relevant risk factors for infection and mortality were explored. Results The overall incidence of infections was 17.6％ in 1670 hospitalized cirrhotic patients. Among the recruited 208 patients in this study, alcoholic, viral hepatitis B or C and autoimmune liver diseases accounted for 29.8％ (62/208), 26.0％ (54/208), and 22.1％ (46/208), respectively. The most common infection site was respiratory tract (70.2％ ), followed by urinary tract, intestinal and intra-abdomen. Forty-six pathogens were isolated from 32 patients, including 22 (47.8％ ) Gram negative bacteria, 16 (34.8％ ) Gram positive bacteria and 2(4.3％ ) mycobacterium tuberculosis, 5 (10.9％) fungi and 1 (2.2％) mycoplasma. The mortality in patients with nosocomial infections (16.7％,7/42) was higher than that in patients with community-acquired infections (6.0％,10/166, P=0.025). All 17 deaths occurred in decompensated cirrhosis. Multivariate analysis demonstrated that hepatic encephalopathy and prothrombin time were independent risk factors of mortality. Conclusions Patients with decompensated cirrhosis are more susceptible to infections. Hepatic encephalopathy and prothrombin time are independent risk factors for death.

Disease Management ; Humans ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; drug therapy ; surgery

Objective To investigate the diagnostic value of ultrasound and MRI in fetal bronchopulmonary sequestration (BPS). Methods The 7 pregnant women with suspected fetal BPS were examined with a 1.5 T MR unit within 24 h after prenatal ultrasound in Hubei Maternal and Children's Hospital during July 2013 to February 2015. The imaging protocol included half-fourier acquisition single shot turbo SE (HASTE), true fast imaging with steady state precession (True FISP) in axial, frontal and sagittal planes relative to the fetal thorax. Prenatal MRI findings have been compared with postnatal enhanced computed tomography or biopsy. Results The locations of BPS were in left side in 5 cases and in right side in 2 cases. One case was complicated with congenital cystic adenomatoid malformation (CCAM) of lung. Ultrasound showed the intrathoracic mass as a hyperechoic lesion and the feeding artery could be found by Doppler ultrasonography. T2WI could reveal not only the hyperintense lesions with clear boundary, but also the hypointense feeding artery originating from systemic circulation. Compared with pathological examination or enhanced CT, both of the ultrasound and the MRI could locate the lesions;however 2 feeding arteries were misjudged. Conclusions Prenatal ultrasound is the first-choice diagnostic modality for BPS. MRI can demonstrate the location, morphology and the feeding arteries of the fetal BPS, and also estimate the volume of normal lungs, which could be an important supplement to prenatal ultrasound in prenatal diagnosis and prognostic prediction of BPS.