Objective To investigate the clinical efficacy of immunotherapy in stroke.Methods CNKI,VIP,Wanfang Data,CBM,the Cochrane Library,Embase,PubMed,and Web of Science databases were searched for random-ized controlled trials on immunotherapy for stroke published from 2000 to 2022,and RevMan5.3 and Stata14 were used for quality assessment and network meta-analysis.Results A total of 11 articles with 2 742 patients were included.The meta-analysis showed that compared with the placebo control group,the immune drug intervention group had no significant influence on modified Rankin Scale(mRS)score(P=0.45)and Barthel index(P=0.33)on day 90.The network meta-analysis showed that compared with the placebo group,there was a tendency of increase in the proportion of patients with an mRS score of 0-1 in the groups of GSK249320(OR=1.33,95%CI 0.48?3.67,P>0.05),Abciximab(OR=1.20,95%CI 0.69?2.07,P>0.05),and Cyclosporine(OR=1.07,95%CI 0.39?2.95,P>0.05),and there was a tendency of increase in Barthel index in the groups of IL-1Ra(OR=1.22,95%CI 0.75?1.96,P>0.05)and Abciximab(OR=2.75,95%CI 0.36?20.96,P>0.05).The largest surface under the cumulative ranking curve(SUCRA)of mRS score was ob-served for GSK249320,followed by Abciximab,Cyclosporine,Placebo,IL-1Ra,Natalizumab,and Enlimomab,and the largest SUCRA of Barthel index was observed for IL-1Ra,followed by Abciximab,Placebo,and Natalizumab.Conclusion Compared with placebo,immunotherapy does not show a better efficacy in the treatment of stroke,which may be associated with the inadequate understanding of the spatiotemporal dynamics and individualized characteristics of stroke immunity and a lack of systematic and comprehensive immunotherapy regimens.

This article reviews the demand, development process, aid types, effects, and existing problems of decision aids for colorectal cancer. The aim is to provide reference for the development of convenient and efficient decision aids for colorectal cancer diagnosis and treatment in China, and to improve the quality of treatment decisions for colorectal cancer patients.

Objective:To study the role of ML-SA5, an agonist of the lysosomal Ca 2+ channel transient receptor potential mucolipin 1 (TRPML1), in promoting lysosomal exocytosis to facilitate intracellular uranium removal and alleviate uranium-induced cellular damage for human renal proximal tubule epithelial cells (HK-2) exposed to uranyl acetate. Methods:HK-2 cells were divided into the following groups to be exposed to uranyl acetate at either 0 or 300 μmol/L for 24 h, followed by treatment with ML-SA5 and/or the lysosomal exocytosis inhibitor vacuolin-1 for 0.5 h: control group (Ctrl group), ML-SA5 group (M group), vacuolin-1 group (V group), ML-SA5 plus vacuolin-1 group (M+ V group), uranium exposure group (U group), uranium exposure plus ML-SA5 group (U+ M group), uranium exposure plus vacuolin-1 group (U+ V group), and uranium exposure plus ML-SA5 plus vacuolin-1 group (U+ M+ V group). We localized lysosome-associated membrane protein-1 (LAMP-1) on the plasma membrane (surface LAMP-1) by immunofluorescence assay; measured intracellular uranium content by inductively coupled plasma mass spectrometry; measured the level of kidney injury molecule-1 (KIM-1) by immunofluorescence assay; measured the rate of cell death with Calcein-AM/PI double staining; determined the subcellular localization of transcription factor EB (TFEB) and the levels of LAMP-1 and TRPML1 proteins by immunofluorescence assay; and measured the number of lysosomes using LysoTracker probes.Results:Compared with the Ctrl group, the U group showed significant increases in the surface LAMP-1 protein level ( t = 12.86, P < 0.05), KIM-1 protein level ( t = 18.86, P < 0.05), cell death rate ( t = 38.53, P < 0.05), TFEB nuclear translocation ( t = 9.12, P < 0.05), the protein expression levels of TFEB’s downstream target genes LAMP-1 ( t = 16.47, P < 0.05) and TRPML1 ( t = 32.33, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 7.75, P < 0.05). Compared with the U group, the U+ M group showed a significantly increased surface LAMP-1 level ( t = 3.33, P < 0.05) and significant decreases in the intracellular uranium level ( t = 5.01, P < 0.05), KIM-1 protein expression level ( t = 3.81, P < 0.05), and cell death rate ( t = 3.24, P < 0.05); all these effects in the U+ M group could be neutralized by the lysosomal exocytosis inhibitor vacuolin-1; and in addition, ML-SA5 significantly increased TFEB nuclear translocation ( t = 9.20, P < 0.05), the protein expression levels of LAMP-1 ( t = 3.05, P < 0.05) and TRPML1 ( t = 3.17, P < 0.05), and the number of lysosomes labeled with LysoTracker probes ( t = 3.13, P < 0.05). Conclusions:The TRPML1 agonist ML-SA5 can promote lysosomal exocytosis to enhance intracellular uranium clearance and reduce uranium-induced cellular damage/death in uranium-loaded HK-2 cells, through activating TFEB to up-regulate lysosome biogenesis and TRPML1 protein expression.

Objective To analyze the effect of microRNA-22-3p (miR-22-3p) of extracellular vesicles derived from bone marrow mesenchymal stem cells on premature ovarian failure. Methods Follicular fluids were provided by premature ovarian failure patients with in vitro fertilization or the second-generation in vitro fertilization treatment and normal volunteers with the same treatment for infertility due to male factors; the exosomes derived from bone marrow mesenchymal stem cells were isolated by differential centrifugation; the morphology, particle size and marker proteins of isolated exosomes were analyzed by transmission electron microscopy, NanoSight LM10 analyzer and Western blotting. Granulosa cells were treated with cyclophosphamide (CTX), exosomes, miR-22-3 mimics and corresponding controls, and were divided into CTX group, control group, exosome incubation group, PBS treatment group, CTX+miR-22-3p group, CTX+miR-NC group, CTX+Exosomes group, and CTX+PBS group; gene expression was detected by Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR). The 3-(4, 5-Dimethylthazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reagent and flow cytometry were used to detect cell viability and apoptosis. Results The extracted exosomes had typical goblet vesicles, the exosome marker proteins C cluster of differentiation 63 (CD63) and C cluster of differentiation 9 (CD9) were expressed in the extracted exosomes, and exosome particle size was 80 to 150 nm; miR-22-3p was significantly lowly expressed in patients with premature ovarian failure and ovarian granulosa cells induced by CTX (P < 0.05), but was significantly highly expressed in ovarian granulosa cells incubated with exosomes derived from bone marrow mesenchymal stem cells (P < 0.05); the activity of granulosa cells in the CTX group was significantly lower than that in the control group, but was significantly higher in the CTX+miR-22-3p group or CTX+Exosomes group than that in the control group (P < 0.05); the apoptosis rate of granulosa cells in the CTX group was significantly higher than that in the control group, but was significantly lower in the CTX+miR-22-3p or CTX+Exosomes group than that in the control group (P < 0.05). Conclusion The miR-22-3p of extracellular vesicles derived from bone marrow mesenchymal stem cells can inhibit ovarian granulosa cell injury induced by CTX.

【Objective】 To investigate the clinical characteristics and prognostic factors of small cell carcinoma of bladder (SCCB), and to explore the efficacy of neoadjuvant therapy. 【Methods】 Clinical information of 47 SCCB patients were retrospectively collected, and the clinical and pathological features were compared with those of urothelial carcinoma (UBC). The prognostic factors and efficacy of neoadjuvant therapy were also investigated. 【Results】 SCCB had higher baseline tumor staging, and was more likely to invade the muscle (100%) and metastasize distantly (21.3%). The overall survival was poor (median: 13.1 months, 1-year survival rate: 53.7%, 5-year overall survival rate: 15.4%). Tumor T staging was a risk factor for SCCB, while neoadjuvant therapy was an independent protective factor that significantly reduced the risk of recurrence and metastasis (HR: 0.189, 95%CI: 0.051-0.697, P=0.012) and death (HR: 0.177, 95%CI: 0.045-0.698, P=0.013), and significantly improved disease-free survival and overall survival. In addition, compared with neoadjuvant chemotherapy alone, neoadjuvant chemotherapy combined with immunotherapy could improve the pathological complete response rate. 【Conclusion】 SCCB is highly malignant and prone to metastasis, and has a poor prognosis. Neoadjuvant therapy combined with radical cystectomy is recommended as the first-line treatment.

Objective:To understand the identification value of pointing gestures in children with autism spectrum disorder(ASD) and its relationship with functional development.Methods:From December 2020 to November 2021, 1 099 children from Children’s Health Care Center of Beijing Children’s Hospital were tested by pointing gestures test, including 942 ASD children and 157 typical developed children.And the data of children's neuropsychological development scale from 800 children aged 1.0-5.9 were collected.SPSS 20.0 was used for statistical analysis. Trend test was used to analyze the distribution of pointing gestures test sensitivity in autistic children, and ANOVA was used to analyze the relationship between pointing gestures test scores and functional development fields.Results:The sensitivity of pointing gestures was 83.5% in children aged 1.0-10.0 years, 76.3%-93.1% in children aged 1.0-4.9 years, and 93.1%-95.1% in children aged 1.0-2.9.With the increase of age, the sensitivity of pointing gestures in autistic children (linear-by-linear association =164.889, P<0.001) and the Yoden index had a decreasing trend. The positive predictive value (91.53%-100.00%) and negative predictive value (75.36%-91.84%) were found in the children aged 1.0-10.0 years.The sensitivity of pointing gestures test was 44.9% in children with mild autism aged 1.0-10.0 years and 46.5%-65.9% in children with mild autism aged from 1.0-3.9 years. The sensitivity of pointing gestures test was 81.5% in children with moderate autism aged from 1.0-10.0 years and 87.3%-97.8% in children with moderate autism aged 1.0-3.9 years. The sensitivity of the pointing gestures test was 97.2% in children with severe autism aged 1.0-10.0 years, and 100.0% in children with severe autism aged 1.0-3.9 years. The sensitivity of the pointing gestures in mild, moderate and severe autism children decreased with age (linear-by-linear association values were 16.725, 64.232, 66.732 respectively, all P<0.001). The children with severe autism mainly scored 2 points (80.3%, 419/522) on the pointing gestures test , and children with moderate autism mainly scored 1 point(64.2%, 170/265) on the pointing gestures test. There were significant differences in functional development among different pointing gestures test groups.Functional development score in the autism children with 0 score of pointing gestures test was significantly higher than those with 1 score and 2 scores of pointing gestures test (all P<0.05). Conclusion:Pointing gestures has good sensitivity in children with autism (especially 1.0-4.9 years of age), and may serve as an objectively observable screening method. The better children with autism score on the pointing gestures, the better their functional development.

Objective:To explore the mechanism of lysosomal membrane permeabilization(LMP)inuranyl acetate-induced death of human kidney proximal tubular epithelial HK-2 cells.Methods:HK-2 cells were exposed to uranyl acetate at concentrations of 100, 300 and 600 μmol/L for 24 h, then in tracellular reactive oxygen species (ROS)and mitochondrial superoxide were measured by DCFH-DA and MitoSOX probe, respectively. HK-2 cells were divided into four groups: blank control group, NAC or CA-074 Me group, uranyl acetate exposure group and uranyl acetate exposure plus NAC or CA-074 Me group. Two-color immune of luorescence staining was used to detect the co-localization of galectin-1 and lysosomal associated membrane protein-1 (LAMP-1) to measure the extent of LMP, and to detect the non- co-localization of cathepsin B and LAMP-1 to reflect the release of cathepsin B in lysosomes. Calcein-AM/PI double staining method was used to detect cell death. One-color immune of luorescence staining of cleaved-caspase-3 expression was used to detect apoptosis. Results:Intracellular ROS and mitochondrial superoxide levels were significantly increased in HK-2 cells after exposure with 100, 300 and 600 μmol/L uranyl acetate for 24 h, about 1.1-2.5 times or 4.0-28 times, respectively( tROS=17.98, 11.84, 11.75, P< 0.05; tmitochondrial superoxide=6.14, 16.02, 13.06, P< 0.05), and they also increased with uranyl acetate concentrations ( tROS=10.10, 10.37, 5.59, P< 0.05; tmitochondrial superoxide=21.50, 15.16, 5.93, P< 0.05). The percentage of co-localization of galectin-1 and LAMP-1 and the percentage of non- co-localization of cathepsin B and LAMP-1 were markedly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, 5.4-6.7 times or 1.5-2.1 times, respectively ( tGalectin-1=15.85, 12.70, P< 0.05; tCathepsin B=5.95, 6.69, P< 0.05), but these increases were inhibited by NAC ( tGalectin-1=4.74, P<0.05; tCathepsin B=4.51, P< 0.05). Moreover, the cell death rate and the cleaved-caspase-3 expression level were also significantly increased in HK-2 cells after exposure with 600 μmol/L uranyl acetate for 24 h, about 28-47 times or 2.4-6.0 times, respectively( tPI=30.40, 10.34, P<0.05; tCleaved-caspase-3=18.49, 9.52, P<0.05), and these increases were obviously diminished by CA-074 Me ( tPI= 6.76, P<0.05; tCleaved-caspase-3=13.47, P<0.05). Conclusions:Exposure to uranyl acetate induces a burst of intracellular ROSthat leads to LMP and consequently causes leakage of cathepsin B from lysosomes to cytoplasm, in turn triggering the lysosomal-dependent cell death and mitochondrial-regulated apoptosis of HK-2 cells.

Objective:To analyze the invasion characteristics and prognostic factors of patients with Masaoka-Koga stage Ⅲ thymoma.Methods:The tumor invasion characteristics of 179 patients who were diagnosed with Masaoka-Koga stage Ⅲ thymoma and treated in Affiliated Cancer Hospital of Zhengzhou University from January 2000 to June 2018 were analyzed retrospectively. According to the treatment methods, all patients were divided into the radical operation group ( n=94), palliative operation group ( n=39) and simple biopsy group ( n=46). The χ2 test was used to compare the classified variables, Kaplan- Meier method was utilized to calculate the cumulative survival rate, log-rank method was used for group comparison and univariate analysis, and Cox’s regression model was used for multivariate analysis. Results:Mediastinal pleural invasion (86.0%) was the most common site, followed by pericardium (50.8%), great vessel (40.8%) and lung (36.3%). The proportion of macrovascular invasion in the radical operation group was 14.9%, significantly lower than 79.5% and 60.9% in the palliative surgery group and biopsy group (both P<0.001). Multivariate analysis showed that the nature of operation ( P<0.001), age ( P=0.011), radiotherapy ( P=0.020) were the independent factors affecting overall survival (OS), while nature of operation ( P<0.001), age ( P=0.004), radiotherapy ( P=0.020), number of invasive organs ( P=0.023) and pathological type ( P=0.016) were the independent factors affecting progress-free survival (PFS). Conclusions:For patients with Masaoka-Koga stage Ⅲ thymoma, mediastinal pleura is the most common site of invasion, pericardium, lung and great vessels are also commonly invaded. The invasion of mediastinal pleura, pericardium and lung exerts slight effect on surgical resectability, whereas great vessel involvement can significantly affect surgical resectability. OS and PFS in patients undergoing radical resection are significantly better than those in patients treated with palliative resection and biopsy. Radical resection is the most important factor affecting prognosis.

Objective:To investigate the correlation between social and linguistic parenting behaviors and developing capability of children with autism.Methods:From August 2020 to December 2020, the social and linguistic parenting behaviors of 302 parents of children diagnosed with autism were investigated in the outpatient department of the hospital.Meanwhile, the data of Gesell scale for children, the social life competence scale for infant and junior middle school students, the autism behavior checklist and the Cancy autism behavior scale were collected.SPSS 20.0 software was used for statistical analysis.Independent sample t test and analysis of variance were used to compare the social and linguistic parenting behaviors of different parents.Pearson correlation analysis was used to analyze the correlation between the social and linguistic parenting behaviors of parents and children's developmental ability and symptom severity. Results:There were no statistically significant differences in children's social and language development parenting behavior between father and mother ( t=1.033, P=0.303; t=-0.312, P=0.756). There were no statistically significant differences in children's social and linguistic parenting behaviors between fathers of different age groups ( F=1.425, P=0.244; F=1.127, P=0.345). Among mothers of different age groups, the social parenting behaviors of <30 years old and 30-34 years old groups were significantly better than those of 35-39 years old group ( F=3.374, P=0.019; LSD: P=0.010, P=0.006). Among fathers, the social parenting behavior( F=4.346, P=0.008; LSD: P=0.020, P=0.001) and social + linguistic parenting behavior in the graduate group and college group were significantly better than those in the high school/vocational group( F=3.965, P=0.012; LSD: P=0.020, P=0.002). Among mothers, the social parenting behavior ( F=2.812, P=0.040; LSD: P=0.008, P=0.023, P=0.009), linguistic parenting behavior ( F=3.769, P=0.011; LSD: P=0.010, P=0.025, P=0.001), social + linguistic parenting behavior ( F=3.654, P=0.013; LSD: P=0.005, P=0.015, P=0.002) in graduate and above groups were significantly better than those in college group, high school/vocational group, junior high school and below groups.The scores of social parenting behavior(40.72±6.80), linguistic parenting behavior(27.20±5.22), and social + linguistic parenting behavior(67.92±11.10) were significantly correlated with children’s fine motor(61.75±16.41)( r=0.193, P=0.001; r=0.153, P=0.009; r=0.190, P=0.001), cognition(68.28±16.83)( r=0.231, P=0.000; r=0.186, P=0.001; r=0.229, P=0.000), language(53.01±18.55) ( r=0.262, P=0.000; r=0.305, P=0.000; r=0.304, P=0.000) and social self-care(61.44±17.85) ( r=0.264, P=0.000; r=0.238, P=0.000; r=0.274, P=0.000). The scores of linguistic parenting behavior and social + linguistic parenting behavior were correlated with children's social life ability (8.65±0.89) ( r=0.142, P=0.046; r=0.140, P=0.049). There was no significant correlation between social parenting behavior, linguistic parenting behavior, social + linguistic parenting behavior and the scores of ABC scale (50.53±21.39) ( r=-0.089, P=0.336; r=-0.115, P=0.215; r=-0.107, P=0.250) and CABS scale (13.96±4.54) ( r=-0.050, P=0.490; r=-0.059, P=0.411; r=-0.058, P=0.421). Conclusions:The social and linguistic parenting behaviors are related to their age and educational level, and are significantly correlated to developing capability of children with autism, but have nothing to do with the severity of children's symptoms.

Objective To explore the inclusion criteria of community-based palliative care service.Methods From July 2017 to September 2017,three rounds of Delphi consultation for development of inclusion criteria of community-based palliative care was conducted.With judgment sampling method,23 senior executives and managers from 6 pilot units of palliative care service in Shanghai were selected and invited to participate in the consultation,which included the importance,coercion and completeness of the inclusion criteria.According to the consulting results,the inclusion criteria of community palliative care services was developed.Results The median age of experts was 35 years (29-55 years,with a quartile spacing of 7 years).The average working experience of experts was (13.7 ± 7.5) years,in which that for palliative care was (4.1 ± 1.6) years.The authority coefficient was 0.82,and the Kendall coordination coefficient was 0.337 (P＜0.01) for the importance of inclusion criteria.In the developed criteria,the four mandatory inclusion criteria were patient needs,the provision ability of community health service centers,compliance with legal requirements and compliance with the concept of palliative care service;and the five non-mandatory inclusion criteria were heavy needs and demands,high cooperation from patients and their families,high satisfaction of patients and their families,within the scope of community health service centers and clinical guidelines for the operations.Conclusion The experts of this research have high enthusiasm and authority,and the developed inclusion criteria of community palliative care service contents are reasonable and feasible.This studymay provide reference for setting up the contents adjustment mechanism of community-based palliative service.