Objective: To investigate whether syndecan-2(SDC2) can affect the proliferation, invasion and migration of cervical cancer cells by regulating ferroptosis and its possible mechanism. Methods : Normal cervical epithelial cells H8 and cervical squamous carcinoma cells C33A were cultured and divided into H8 group and C33A group. C33A cells were cultured and divided into control group, low SDC2 expression group, SDC2+ferroptosis inhibitor(ferrostation-1) group and SDC2 + ferroptosis inducer(erastin) group. Western blot was used to detect the protein levels of SDC2, solute carrier family 7 member 11(SLC7A11) and glutathione peroxidase 4(GPX4). RT-qPCR was used to detect the SDC2 mRNA level in C33A cells. ELISA kits were used to detect the levels of reactive oxygen species(ROS), glutathione(GSH) and ferrous ion(Fe2+) in C33A cells. The cloning ability of C33A cells was detected by plate cloning. The migration ability of C33A cells was detected by scratch test. Transwell assay was used to detect the invasion ability of C33A cells. Results : Compared with H8 group, the protein and mRNA expressions of SDC2, SLC7A11 and GPX4 in C33A group increased(P<0.05). Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells in the low SDC2 group decreased(P<0.05), the protein and mRNA expressions of SLC7A11 and GPX4 in C33A cells decreased(P<0.05), and the GSH level decreased. ROS and Fe2+levels increased(P<0.05). Compared with the low SDC2 group, the protein and mRNA expressions of SLC7A11 and GPX4 increased(P<0.05), the GSH level increased, and the ROS and Fe2+levels decreased(P<0.05) in the low SDC2+ferrostation-1 group. Compared with the control group, the proliferation ability, migration ability and invasion ability of C33A cells with low SDC2+erastin expression decreased(P<0.05). Conclusion The expression of SDC2 increases in C33A cervical cancer cells. Low expression of SDC2 can activate SLC7A11/GPX4 pathway mediated ferroptosis, thereby reducing the proliferation, invasion and migration of C33A cells.

Clinical practice guidelines represent the best recommendations for patient care. They are developed through systematically reviewing currently available clinical evidence and weighing the relative benefits and risks of various interventions. However, clinical practice guidelines have to go through a long translation cycle from development and revision to clinical promotion and application, facing problems such as scattered distribution, high duplication rate, and low actual utilization. At present, the clinical practice guideline information platform can directly or indirectly solve the problems related to the lengthy revision cycles, decentralized dissemination and limited application of clinical practice guidelines. Therefore, this paper systematically examines different types of clinical practice guideline information platforms and investigates their corresponding challenges and emerging trends in platform design, data integration, and practical implementation, with the aim of clarifying the current status of this field and providing valuable reference for future research on clinical practice guideline information platforms.

Objective To investigate the dosimetric differences of different types of multileaf collima-tors(MLCs)on the planning target volume(PTV)and organs at risk(OARs)in volumetric modulated arc therapy(VMAT)for cervical cancer.Methods Twenty postoperative patients with cervical cancer receiving radiotherapy in this hospital from May 2023 to January 2024 were selected as the study subjects.For each pa-tient,two kinds of VMAT plans(MLCi2-MLC and AgilityTM-MLC)after cervical cancer operation were de-signed.The dosimetric parameters of the planning target volume(PTV),exposure dose by organs at risk(OAR),y passing rate and monitor units(MU)were compared between the two plans.Results Compared with MLci2-MLC,prescription dose(V45),conformity index(CI)and homogeneity index(HI)in AgilityTM-MLC were better,and the differences were statistically significant(P＜0.05),Compared with MLCi2-MLC,bladder V30,V40,average dose(Dmean),rectal V10,V20,V30,left femoral head V10,Dmean and small intestine V10,V30,Dmean and Dmax were lower,bladder V45,rectal V45,right femoral head V20 were higher,and the differences were statistically significant(P＜0.05).Compared with MLCi2-MLC,the y passing rate in AgilityTM-MLC was lower[(98.31±0.64)％vs.(99.73±0.37)％],and the difference was statistically significant(P＜0.05);while MU had no statistical difference between AgilityTM-MLC and MLCi2-MLC(996.74±65.46 vs.996.80±49.77,P＞0.05).Conclusion AgilityTM-MLC demonstrates better PTV conformity and homogenei-ty,as well as good protection on OARs in both high and low dose regions.

Objective:This study aims to explore the relationship between the abundance of Lachnoclostridium genus in the gut microbiome and inflammatory markers with cognitive impairment in patients with first-episode schizophrenia. Methods:A total of 87 medication-naive patients with first-episode schizophrenia (patient group) and 87 matched healthy controls (control group) who visited the Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022 were selected for this study. A 24-week follow-up was conducted for the patients, and all patients received treatment with risperidone. Venous blood and fecal samples were collected from the subjects at baseline and week 24 to measure the levels of superoxide dismutase-1, erythrocyte sedimentation rate, and the abundance of Lachnoclostridium. The severity of symptoms in patients with schizophrenia was assessed using the Positive and Negative Syndrome Scale, and the cognitive function of all subjects was evaluated using MATRICS Consensus Cognitive Battery tests. The differences in the abundance of Lachnoclostridium, inflammatory markers, and cognitive scores between groups were analyzed using t-tests, and the correlations between Lachnoclostridium abundance, inflammatory markers, and cognitive scores were analyzed using Pearson correlation analysis. Results:(1) At baseline, compared with the control group, patients with first-episode schizophrenia had lower levels of superoxide dismutase-1( t=6.83, P<0.001) and total cognitive function test scores( t=6.35, P<0.001), and higher abundance of Lachnoclostridium( Z=-4.64, P<0.001). (2) At baseline, the levels of superoxide dismutase-1 in patients with first-episode schizophrenia were positively correlated with social cognition( r=0.30, P=0.005), while erythrocyte sedimentation rate was negatively correlated with information processing speed and social cognition( r=-0.23, -0.31, both P<0.050). The abundance of Lachnoclostridium genus was negatively correlated with speed of processing( r=-0.28, P=0.009), working memory( r=-0.22, P=0.040), and visual memory( r=-0.32, P=0.003). (3) After 24 weeks of risperidone treatment, the levels of superoxide dismutase-1( t=-2.07, P=0.045) and total cognitive function test scores( t=-3.47, P=0.001) increased in patients, while erythrocyte sedimentation rate( t=2.21, P=0.033) decreased. The abundance of Lachnoclostridium genus showed a decreasing trend( Z=1.52, P=0.128) and did not differ significantly from the control group( Z=1.68, P=0.094). (4) Among the 39 patients who completed the 24-week follow-up, the baseline abundance of Lachnoclostridium genus was negatively correlated with attention and vigilance( r=-0.39, P=0.014) and total cognitive function test scores( r=-0.34, P=0.032) at week 24. The baseline erythrocyte sedimentation rate was positively correlated with the differences in speed of processing, working memory, social cognition, and total cognitive function test scores between baseline and week 24( r=0.42, 0.32, 0.41, 0.36, all P<0.050). (5) At baseline, the abundance of Lachnoclostridium genus had predictive value for erythrocyte sedimentation rate( r=0.45, P=0.004), attention and vigilance( r=-0.39, P=0.014), and total cognitive function test scores( r=-0.34, P=0.032) at week 24. Conclusion:In first-episode schizophrenia patients, there is a significant correlation between the abundance of gut Lachnoclostridium and inflammation and cognitive function.

Objective:To explore the role of interaction between stearidonic acid (SDA) and fatty acid desaturase 2 ( FADS2) rs174570 genotyping in the cognitive function of schizophrenia (SCH). Methods:This study is a case-control study, patients with first-episode, drug-na?ve schizophrenia were recruited from the First Affiliated Hospital of Zhengzhou University′s Department of Psychiatry from October 2017 to October 2019. Healthy controls were recruited through advertisements and medical examinations during the same period. Peripheral blood SDA levels of the SCH patient group and the control group were measured and compared using liquid chromatograph-mass spectrometer (LC-MS), and paired sample t-test was conducted to analyze the changes in the patient group before and after treatment with risperidone. Genome-wide association study (GWAS) was used for analyzing the key enzyme of SDA, and analysis of variance was performed to evaluate the relationship between FADS2 single nucleotide polymorphism (SNP) genotyping and the level of SDA. The Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) were used to assess the severity of psychotic symptoms and cognitive function, the comparison between the two groups was conducted by independent sample t-test, and the changes before and after risperidone treatment were analyzed by paired sample t-test. Linear regression analysis was performed to investigate the relationship between the interaction of SDA and FADS2 rs174570 genotyping, and cognitive impairment in SCH. Results:SDA levels were significantly lower in the SCH group compared to the control group ( t=-10.67, P<0.001). Cognitive score in patients with SCH were lower than that of HCs ( t=-10.30—-3.30, P<0.05 for all). Low levels of SDA in patients with SCH were positively correlated with the score of speed of processing (SOP; r=0.406, P<0.001) at baseline. After six months of treatment with risperidone, serum levels of SDA increased from (3.6±1.9) μmol/L to (4.4±2.3) μmol/L, and paired t-tests showed significant difference ( t=-2.29, P=0.024). The change of SDA levels before and after risperidone treatment was positively correlated with the change of SOP scores ( r=0.327, P=0.002). FADS2 rs174570 genotyping were significantly associated with SDA levels ( F=3.74, P=0.027) and cognitive function scores of SOP ( F=4.28, P=0.017), and attention/vigilance (AV; F=6.74, P=0.002). Pairwise comparisons showed that CC carriers of rs174570 genotype had higher SDA levels than CT and TT carriers ( P=0.024, and 0.048, respectively), and higher total scores of SOP, AV and MCCB than CT carriers ( P=0.006, 0.001, and 0.002, respectively). The interaction of SDA and FADS2 rs174570 genotyping were associated with cognitive function SOP scores in patients with SCH (β=1.82, P=0.029). Conclusion:The interaction of SDA and FADS2 rs174570 genotyping is associated with the cognitive function in patients with SCH.

Objective:This study aims to explore the relationship between the abundance of Lachnoclostridium genus in the gut microbiome and inflammatory markers with cognitive impairment in patients with first-episode schizophrenia. Methods:A total of 87 medication-naive patients with first-episode schizophrenia (patient group) and 87 matched healthy controls (control group) who visited the Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022 were selected for this study. A 24-week follow-up was conducted for the patients, and all patients received treatment with risperidone. Venous blood and fecal samples were collected from the subjects at baseline and week 24 to measure the levels of superoxide dismutase-1, erythrocyte sedimentation rate, and the abundance of Lachnoclostridium. The severity of symptoms in patients with schizophrenia was assessed using the Positive and Negative Syndrome Scale, and the cognitive function of all subjects was evaluated using MATRICS Consensus Cognitive Battery tests. The differences in the abundance of Lachnoclostridium, inflammatory markers, and cognitive scores between groups were analyzed using t-tests, and the correlations between Lachnoclostridium abundance, inflammatory markers, and cognitive scores were analyzed using Pearson correlation analysis. Results:(1) At baseline, compared with the control group, patients with first-episode schizophrenia had lower levels of superoxide dismutase-1( t=6.83, P<0.001) and total cognitive function test scores( t=6.35, P<0.001), and higher abundance of Lachnoclostridium( Z=-4.64, P<0.001). (2) At baseline, the levels of superoxide dismutase-1 in patients with first-episode schizophrenia were positively correlated with social cognition( r=0.30, P=0.005), while erythrocyte sedimentation rate was negatively correlated with information processing speed and social cognition( r=-0.23, -0.31, both P<0.050). The abundance of Lachnoclostridium genus was negatively correlated with speed of processing( r=-0.28, P=0.009), working memory( r=-0.22, P=0.040), and visual memory( r=-0.32, P=0.003). (3) After 24 weeks of risperidone treatment, the levels of superoxide dismutase-1( t=-2.07, P=0.045) and total cognitive function test scores( t=-3.47, P=0.001) increased in patients, while erythrocyte sedimentation rate( t=2.21, P=0.033) decreased. The abundance of Lachnoclostridium genus showed a decreasing trend( Z=1.52, P=0.128) and did not differ significantly from the control group( Z=1.68, P=0.094). (4) Among the 39 patients who completed the 24-week follow-up, the baseline abundance of Lachnoclostridium genus was negatively correlated with attention and vigilance( r=-0.39, P=0.014) and total cognitive function test scores( r=-0.34, P=0.032) at week 24. The baseline erythrocyte sedimentation rate was positively correlated with the differences in speed of processing, working memory, social cognition, and total cognitive function test scores between baseline and week 24( r=0.42, 0.32, 0.41, 0.36, all P<0.050). (5) At baseline, the abundance of Lachnoclostridium genus had predictive value for erythrocyte sedimentation rate( r=0.45, P=0.004), attention and vigilance( r=-0.39, P=0.014), and total cognitive function test scores( r=-0.34, P=0.032) at week 24. Conclusion:In first-episode schizophrenia patients, there is a significant correlation between the abundance of gut Lachnoclostridium and inflammation and cognitive function.

Objective:To explore the role of interaction between stearidonic acid (SDA) and fatty acid desaturase 2 ( FADS2) rs174570 genotyping in the cognitive function of schizophrenia (SCH). Methods:This study is a case-control study, patients with first-episode, drug-na?ve schizophrenia were recruited from the First Affiliated Hospital of Zhengzhou University′s Department of Psychiatry from October 2017 to October 2019. Healthy controls were recruited through advertisements and medical examinations during the same period. Peripheral blood SDA levels of the SCH patient group and the control group were measured and compared using liquid chromatograph-mass spectrometer (LC-MS), and paired sample t-test was conducted to analyze the changes in the patient group before and after treatment with risperidone. Genome-wide association study (GWAS) was used for analyzing the key enzyme of SDA, and analysis of variance was performed to evaluate the relationship between FADS2 single nucleotide polymorphism (SNP) genotyping and the level of SDA. The Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) were used to assess the severity of psychotic symptoms and cognitive function, the comparison between the two groups was conducted by independent sample t-test, and the changes before and after risperidone treatment were analyzed by paired sample t-test. Linear regression analysis was performed to investigate the relationship between the interaction of SDA and FADS2 rs174570 genotyping, and cognitive impairment in SCH. Results:SDA levels were significantly lower in the SCH group compared to the control group ( t=-10.67, P<0.001). Cognitive score in patients with SCH were lower than that of HCs ( t=-10.30—-3.30, P<0.05 for all). Low levels of SDA in patients with SCH were positively correlated with the score of speed of processing (SOP; r=0.406, P<0.001) at baseline. After six months of treatment with risperidone, serum levels of SDA increased from (3.6±1.9) μmol/L to (4.4±2.3) μmol/L, and paired t-tests showed significant difference ( t=-2.29, P=0.024). The change of SDA levels before and after risperidone treatment was positively correlated with the change of SOP scores ( r=0.327, P=0.002). FADS2 rs174570 genotyping were significantly associated with SDA levels ( F=3.74, P=0.027) and cognitive function scores of SOP ( F=4.28, P=0.017), and attention/vigilance (AV; F=6.74, P=0.002). Pairwise comparisons showed that CC carriers of rs174570 genotype had higher SDA levels than CT and TT carriers ( P=0.024, and 0.048, respectively), and higher total scores of SOP, AV and MCCB than CT carriers ( P=0.006, 0.001, and 0.002, respectively). The interaction of SDA and FADS2 rs174570 genotyping were associated with cognitive function SOP scores in patients with SCH (β=1.82, P=0.029). Conclusion:The interaction of SDA and FADS2 rs174570 genotyping is associated with the cognitive function in patients with SCH.

Objectives:To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention.Methods:Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test.Results:Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ 2=4.261, 6.930, P=0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n=211, 93%) cause of this condition. c.729_730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ 2=3.859, P=0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ 2=13.729, P=0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ 2=4.789, 7.705, P=0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions:The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objectives To observe the effect of amphiregulin (Areg) via lateral ventricle injection on focal cerebral ischemia/reperfusion (I/R) injury in rats and to investigate its possible mechanism. Methods A total of 96 3-month old health specified pathogen free SD rats were randomly divided into 6 groups (n=16 in each group):sham operation group (sham group),only exposure of common carotid artery and bifurcation;I/R group,making I/R model;solvent control group,lateral ventricle injection of standard protein solution(5 μl);Areg group,lateral ventricle injection of Areg(2 μg/5 μl);AG1478 group [AG1478,a blocker of Areg receptor epidermal growth factor receptor(EGFR),lateral ventricle injection of AG1478 (2.5 μg/5 μl);Areg combined AG1478 (AAG) group,lateral ventricle giving AG1478 (2.5 μg/5 μl),and then giving Areg (2 μg/5 μl) after 30 mm.The model of focal cerebral I/R injury was induced after 30 min administration of the above last 4 groups.After 24 h of reperfusion,the volume of cerebral infarction, the neurobehavioral score and the number of apoptotic cells in the brain tissue were compared among the groups. After 6 h of reperfusion,the phosphorylation levels of EGFR and protein kinase B(Akt)in ischemic brain tissue were detected. Results Compared with the sham group,the cerebral infarction volume and the number of apoptotic cells in brain tissue were increased significantly,while the neurobehavioral score was decreased(all P<0.05).Compared with the I/R group,the volume of cerebral infarction,the number of apoptotic cells in the brain tissue were decreased significantly,and the neurobehavioral score was increased in the Areg group,the levels of EGFR and Akt phosphorylation were significantly higher (all P <0. 05). Compared with the I/R group,the volume of cerebral infarction and the number of apoptotic cells of the AG1478 group were increased,the levels of EGFR and Akt phosphorylation were decreased(all P<0.05);Compared with the Areg group,the volume of cerebral infarction and the number of apoptotic cells of the AAG group and AG1478 group were increased significantly,and the levels of EGFR and Akt phosphorylation were decreased significantly(all P<0.05). Conclusions Areg reduces the infarct volume in ischemic brain tissue,improves nerve function,and inhibits apoptosis by activating EGFR-Akt signaling pathway. Therefore,it has some protective effect for cerebral I/R injury.