Objective: To evaluate the efficacy and safety of adding toripalimab to bevacizumab and platinum-based chemotherapy as first-line treatment for refractory recurrent or metastatic (R/M) cervical cancer (CC). Methods: Patients were administered toripalimab (240 mg) + bevacizumab (7.5 mg/kg) combined with platinum-based chemotherapy once every three weeks for six cycles, followed by the maintenance therapy involving toripalimab + bevacizumab once every 3 weeks for 12 months or when disease progression or intolerable toxicity occurred. The primary endpoint was the objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1. The secondary endpoints were safety profiles, disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Results: Twenty-four patients were enrolled in this study and in the final analysis. The median follow-up duration was 18.6 (range, 3.3–28.5) months. The ORR was 83.3% (95% confidence interval [CI]=62.6–95.3) and the DCR was 95.8% (95% CI=78.9–99.9); 9 (37.5%) patients achieved complete response, 11 (45.8%) achieved partial response, and 3 (12.5%) had stable disease. The median PFS was 22.6 (95% CI=10.4–34.7) months and the median OS was not reached. The most common grade 3 treatment-related adverse events (AEs) were neutropenia (41.7%) and leukopenia (16.7%). The most common immune-related AEs (irAEs) were thyroid dysfunction (37.5%) and increased adrenocorticotropic hormone (37.5%) and serum cortisol levels (33.3%). No grade ≥3 irAEs were observed. Conclusion Toripalimab combined with bevacizumab and platinum-based chemotherapy show promising clinical efficacy and favorable safety profile, providing an alternative firstline treatment option for patients with R/M CC.

A wealth of evidence has suggested that gastrointestinal dysfunction is associated with the onset and progression of Parkinson's disease (PD). However, the mechanisms underlying these links remain to be defined. Here, we investigated the impact of deregulation of intestinal dopamine D2 receptor (DRD2) signaling in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurodegeneration. Dopamine/dopamine signaling in the mouse colon decreased with ageing. Selective ablation of Drd2, but not Drd4, in the intestinal epithelium, caused a more severe loss of dopaminergic neurons in the substantia nigra following MPTP challenge, and this was accompanied by a reduced abundance of succinate-producing Alleoprevotella in the gut microbiota. Administration of succinate markedly attenuated dopaminergic neuronal loss in MPTP-treated mice by elevating the mitochondrial membrane potential. This study suggests that intestinal epithelial DRD2 activity and succinate from the gut microbiome contribute to the maintenance of nigral DA neuron survival. These findings provide a potential strategy targeting neuroinflammation-related neurological disorders such as PD.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects* ; Animals ; Disease Models, Animal ; Dopamine ; Dopaminergic Neurons/metabolism* ; Gastrointestinal Microbiome ; Mice ; Mice, Inbred C57BL ; Neuroprotection ; Parkinson Disease ; Pyrrolidines ; Receptors, Dopamine D2/metabolism* ; Substantia Nigra ; Succinates

Objective:To construct a standardized nursing scheme for children with cerebral palsy based on a child- and family-centered nursing model and to evaluate its effect on quality of life and self-care ability of daily life in children with cerebral palsy.Methods:Using the convenient sampling method, a total of 120 children with cerebral palsy and 120 parents who were initially hospitalized for rehabilitation in Department of Rehabilitation Medicine of the First People's Hospital of Urumqi from August 2017 to August 2019 were selected as the research objects. According to the random number table method, the children and primary caregivers were divided into the control group and the observation group, with 60 children and 60 parents in each group. The control group was given routine rehabilitation nursing, while the observation group was given a standardized nursing scheme centered on children and families on the basis of the control group. The improvement of quality of life and daily living ability of children with cerebral palsy before the intervention and 12 weeks after the intervention were compared between the two groups.Results:After intervention, the scores of quality of life and self-care ability in daily life in the observation group were better than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Standardized nursing scheme centered on children and families can improve quality of life and daily self-care ability of children with cerebral palsy, which is worthy of clinical application.

Objective: To explore the application effect of a specialized team consisting of specialist nurses and some emergency care′s or intensive care′s head nurses of critically ill patients in the hospital. Methods: From 2016 to 2018, the Critical Care Professional Group of implemented a provincial and above specialist nurses and the backbone of the specialist care departments of the acute and critical departments. A total of 23 members were composed of core members. A total of 56 liaison officers from each ward were selected to participate. The training and assessment activities presided over by the core staff of the professional group; at the same time, the professional group liaison officer is also the leader of the critical care quality control team in this ward, and implements the quality control of critical care patients; the core members are responsible for the guidance of the nursing care of critical patients in the hospital. The liaison staff carries out the training and assessment of the intensive care knowledge, skills and related nursing standards, norms, as well as the sharing of new technologies and new projects or research topics for acute and critical care, and the training of intensive care posts in the hospital. Before and after the operation of the specialized nursing team, the quality control scores of critically ill patients in 2015-2018, the satisfaction survey of nursing, the number of patents published by nurses in 2-25 years, the mortality rate of patients, and the results of unplanned extubation in 2016-2018 Compare. Results: The quality control scores of critical care patients in 2015-2018 were 93.91±1.23, 94.07±1.38,94.33±1.24, 95.42±1.56. The difference was statistically significant (F=49.597, P < 0.01). Satisfaction survey scores were 94.92±2.28, 97.08±1.37, 97.82±1.52, 97.94±1.68, the difference was statistically significant (F=30.882, P < 0.01); work 2-20 years The number of nurses was 678, 809, 853, and 925 respectively. The number of patents published was 76, 119, 147, and 237, respectively. The difference was statistically significant (χ²=36.77, P < 0.01). 2016-2018 unplanned extubation rate was 4.98‰(127/25 517), 4.01‰(115/28 713), 3.25‰(112/34 493), the difference was statistically significant (χ²=10.958, P <0.01). Conclusions The professional nursing team operation mode can improve the core ability and comprehensive quality of nursing staff's intensive care, improve the quality of care management of critically ill patients, ensure patient safety, and achieve continuous improvement of nursing quality.

Objective To evaluate the clinical effect of milrinone nebulized inhalation for improving intraoperative cardiac function and pulmonary arterial pressure in the patients with chronic obstructive pulmonary disease (COPD) complicating pulmonary hypertension (PH).Methods Forty-four surgical patients with COPD complicating PH in the Chongqing Municipal Medical Emergency Center from June 2015 to June 2016 were chosen,including 23 cases of thoracic surgery,13 cases of abdominal surgery and 8 cases of lower extremity fracture surgery.The patients were divided into the control group and treatment group,22 cases in each group.The control group received the routine comprehensive treatment.In addition receiving the conventional comprehensive treatment,milrinone nebulized inhalation in the treatment group was given before general anesthesia.Both of the two groups were imbedded with floating catheter in the right internal jugular vein for detecting the clinical indexes:cardiac output (CO),pulmonary artery systolic pressure (PASP),pulmonary artery mean pressure (PAMP) and pulmonary capillary wedge pressure (PCWP).Results Compared with before treatment,CO after treatment in the treatment group was significantly increased (P＜0.05),PASP,PAMP and PCWP after treatment in the treatment group were significantly decreased(P＜0.05).CO,PASP,PAMP and PCWP in the control group had no statistical difference between before and after treatment,the difference was not statistically significant (P＞0.05).Conclusion Intraoperative milrinone nebulized inhalation in the patients with COPD complicating PH can effectively improve the patient's cardiopulmonary function.

Objective To explore the correlation between the self-management and self-efficacy of senile patients with chronic heart failure (CHF). Methods In this study, the conveninent sampling method was adopted. From June to December 2016, totally 416 senile CHF patients hospitalized in the Department of Cardiology of 5 general class Ⅲ grade A hospitals in Xi'an were investigated with the general demographic data questionnaire, self-management scale for CHF patients and chronic disease self-efficacy scale. Results The score of self-management in the senile CHF patients in Xi'an totaled (50.76±9.98), with a scoring rate of 63.5%; the scores of medication management, food and beverage management, psychological and social management and symptom management were (13.38±3.38), (7.89±2.14), (12.81±2.91) and (16.69±4.26), with the scoring rates of 66.9%, 65.8%, 64.1% and 59.6%, respectively, showing a medium level; and there was statistically significant difference in the total self-management score between patients with different marital status, per capita income and heart function grading (t=-2.443, 10.906, 16.229;P<0.05). The score of self-efficacy totaled (34.30±11.90), with a scoring rate of 57.17%, showing a medium level. The correlation analysis showed that there was a positive correlation between self-efficacy and self-management (r=0.161, P< 0.05). Conclusions The self-management and self-efficacy of the senile CHF patients in Xi'an remain at a medium level, which could be possibly improved, and the two are closely correlated. The results suggest that we should pay more attention to the patient's management confidence in the disease itself, attach importance to their psychological and social support and enhance their self-efficacy, thus improving their self-management. This is of great significance in controlling CHF and improving the patient's quality of life.

Objective To discover the significance of neurofilament light (NFL) chain of cerebrospinal fluid (CSF), an axonal injury biomarker, in diagnosis and prognosis prediction of neuromyelitis optica spectrum disorders(NMOSD).Methods Sixty-one NMOSD patients and 24 other patients such as neurosis, migraine and so on, with lumbar puncture were enrolled as NMOSD group and normal control (NC) group from in and out patients of Department of Neurology of Navy General Hospital from January 2014 to August 2016. The clinical and neuroimaging features of NMOSD group and CSF samples of both groups were collected,and the NFL levels of CSF were measured by enzyme linked immunosorbent assay. The CSF NFL levels in different subtypes of NMOSD patients were compared, and the influence factors of the NFL levels in CSF were calculated by multiple linear regression analysis. Results The NFL levels of CSF in NMOSD group (2 729.00(14 862.00) pg/ml) were significantly higher than that in NC group ((299.50(308.00) pg/ml, t=8.588, P=0.000;t test of NFL levels was performed after logarithmicly transforming based on 10). There were no statistically significant differences of CSF NFL levels among optic neuritis, longitudinally extensive transverse myelitis and neuromyelitis optica. In NMOSD group, age (b=0.017, P<0.01), Expanded Disability Status Scale score (b=0.078, P<0.05) and enhancement in gadolinium-magnetic resonance imaging (b=0.478, P<0.01) were correlated with the NFL levels of CSF, while gender, courses of diseases and aquaporin 4 antibody in serum were not related to the NFL levels. Conclusion The NFL levels of CSF are conducive to assess the severity and probable progress of NMOSD.

Objective To evaluate the safety and immunogenicity of one booster dose of inactivated hepatitis A vaccine in young adults.Methods The subjects were selected from participants in the clinical trial of immunogenicity of inactivated and attenuated live hepatitis A vaccine in young adults.Eligible subjects were those who had received one dose of inactivated or attenuated hepatitis A vaccine,could be contacted and were sero-negative before primary vaccination.All qualified subjects were immunized with one booster dose of inactivated hepatitis A vaccine.The blood samples were collected before booster dose vaccination and 28 days after the immunization.Anti-HAV antibody titer ≥20 mIU/ml was considered to be sero-protected against hepatitis A virus.Results The GMCs in the inactivated HAV vaccine group and attenuated live vaccine group before booster dose vaccination were 70.80 mIU/ml and 50.12 mIU/ml,respectively,and the sero-protection rates were 94.7％ and 65.0％,respectively.After the vaccination of the booster dose,the sero-protection rates in both groups were 100.0％,and the GMCs were 2 816.09 mIU/ml and 2 654.55 mIU/ml,respectively.Conclusion The GMCs and sero-protection rates of anti-HAV antibody in young adults declined after three years of the primary vaccination.However,the higher GMC and sero-protection rate were observed in the inactivated vaccine group than in the attenuated live vaccine group.Significant increases of GMC levels were observed in both groups after one booster dose vaccination.

Objective To explore the clinical characteristics of infratentorial primary angiitis in central nervous system (PACNS).Methods A total of 5 cases diagnosed as infratentorial PACNS in the neurology department of Navy General Hospital of PLA in 2015 were enrolled in the study.The clinical,imaging and pathological data were collected and analyzed.Results All the 5 cases were male with the median onset age of thirty-four.Five cases presented with dizziness,two with headache,three with walking unstable,two with facial numbness and one with dysarthria.Rising pressure of cerebrospinal fluid (CSF) (190-245 cmH2O,1 cmH2O =0.098 kPa) was found in 4 cases by the lumbar puncture,mildly increased number of leukocyte in 2 cases [(12-28) × 106/L],increased CSF protein in 3 cases(540-979 mg/L) and increased IgG index in 3 cases (0.84-1.45).Pons lesions were revealed by magnetic resonance imaging(MRI) in 4 cases,brachium pontis lesions in 2 cases,cerebellum lesions in 2 cases,one with midbrain lesion in 1 case,unilateral lesions in 4 cases and bilateral lesion in 1 case.Different degree of edema and mass effect were shown in all lesions by MRI.Patch like enhancement was found by contrast MRI in 5 cases and meningeal enhancement in 2 cases.Elevation of choline (Cho) peak was found by magnetic resonance spectroscopy (MRS) in 4 cases,reduction of N-acetyl aspartate (NAA) peak in 3 cases,appearance of lactate peak in 1 case and lipid peak in another case.Arterial spin labeling (ASL) was performed in 4 cases and no hyperperfusion was found.Susceptibility weighted imaging(SWI) was performed in 3 cases and microhemorrhage in the lesions was found in 2 cases and normal in 1 case.Magnetic resonance arteriography(MRA) was performed in 1 case and no stenosis was found.Digital subtraction arteriography(DSA) was performed in 1 case and multiple stenosis of the intracranial arteries was showed.Two cases had taken the stereotactic brain biopsy and the histopathologic diagnosis was angiitis.Five cases were treated with methylprednisolone and cyclophosphamide was added on in 1 case.Good prognosis was found in all cases.Conclusions Infratentorial PACNS mostly attacks middle-aged males.The lesions tend to locate in unilateral pons,brachium pontis,cerebellum and midbrain.Hemorrhage or microhemorrhage in lesions is often found by SWI and no hyperperfusion is shown by ASL,which would be useful to distinguish PACNS from malignant tumors.Given the limitations of brain biopsy in clinical practice,clinical and imaging features would be helpful to diagnose PACNS.

Objective To study the effects of TRβ△ on apoptosis and proliferation of liver cancer cell line RH-35 from rat in vitro. Methods RH-35 cells were transfected by empty vector pcDNA3. 1 and expression plasmid pcDNA3. 1-TRβ△, then exposure to 10 nmol/ L T3 . RH-35 cells apoptosis and proliferation were observed by flow cytometry and MTT colorimetric assay; Levels of catenin β-1(CTNNB1), senescence marker protein-30(SMP-30) and BCL2-antagonist/ killer ( BAK ) mRNA evaluation were detected by quantitative real-time RT-PCR (RT-qPCR). Results In the presence of T3 , overexpression of TRβ△ significantly inhibited the proliferation, increased the percentage of apoptotic, down-regulated CTNNB1and SMP-30 expression, up-regulated BAK expression in RH-35 cells( P < 0. 05). Conclusion TRβ△ could inhibit the proliferation of RH-35 cells and promote their apoptosis, which may be related to upregulation of BAK genes expression and downregulation of CTNNB1 and SMP-30 gene expression, and these effects could be regulated by T3 .