ObjectiveTo investigate the therapeutic effects of the Anemarrhenae Rhizoma water extract （AR） on Alzheimer's disease （AD） model rats and to explore its potential underlying mechanisms. MethodsMale rats were intraperitoneally injected with D-galactose （100 mg·kg^-1） for 42 days， and on day 14， 1 μL of β-amyloid （Aβ_25-35， 2 g·L^-1） solution was injected into the hippocampus. Rats were randomly divided into a model group， low-dose AR （0.6 g·kg^-1）， medium-dose AR （1.2 g·kg^-1）， high-dose AR （2.4 g·kg^-1）， and a positive control group （donepezil， 5 mg·kg^-1）. Healthy rats receiving only a hippocampal injection of 1 μL of sterile saline served as the sham-operated group. From day 21， rats in the treatment groups were administered the corresponding drugs by gavage once daily for 21 consecutive days， while the blank control and model groups received an equal volume of saline. Learning and memory abilities were assessed using the Morris water maze. Brain tissue damage was observed by hematoxylin and eosin （HE） staining， and neuronal apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick-end labeling （TUNEL） staining. Levels of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and interleukin-10 （IL-10） in brain tissues were measured by enzyme-linked immunosorbent assay （ELISA）. BV2 microglial cells were co-cultured with Aβ_25-35 （40 μmol·L^-1） for 2 h， and cell viability was determined by the CCK-8 assay to screen the optimal concentration of AR-containing serum （S-AR）. Cells were divided into blank control， Aβ_25-35， S-AR， EX527 ［silent information regulator 1 （SIRT1） inhibitor］， and S-AR+EX527 groups. Immunofluorescence staining was used to detect the expression of CD16， CD206， and high-mobility group box 1 （HMGB1）. Western blot analysis was performed to measure the protein expression of CD16， inducible nitric oxide synthase （iNOS）， CD206， arginase （Arg）， and proteins related to the SIRT1/HMGB1/nuclear factor-κB （NF-κB） signaling pathway. ResultsIn vivo experiments showed that， compared with the sham-operated group， the model group exhibited reduced platform crossings and time spent in the target quadrant （P<0.01）， prolonged escape latency， increased hippocampal neuronal apoptosis （P<0.01）， and obvious hippocampal damage. The expression levels of IL-6， TNF-α， IL-10， CD16， and iNOS in brain tissues were significantly elevated （P<0.01）， while CD206 and Arg protein expression showed an increasing trend without statistical significance. Compared with the model group， all AR-treated groups significantly increased platform crossings and target quadrant time （P<0.05， P<0.01）， alleviated hippocampal damage， reduced escape latency and neuronal apoptosis， downregulated the expression of TNF-α， IL-6， CD16， and iNOS （P<0.05， P<0.01）， and upregulated the expression of IL-10， CD206 and Arg （P<0.05， P<0.01）. In vitro experiments demonstrated that， compared with the blank control group， the Aβ_25-35 group showed increased fluorescence intensity of CD206， CD16， and HMGB1， as well as elevated protein expression of iNOS and CD16 （P<0.01）， while CD206 and Arg protein expression exhibited an increasing trend without statistical significance. After S-AR intervention， CD206 fluorescence intensity and the protein expression of Arg and CD206 were significantly increased （P<0.01）， whereas the fluorescence intensity of CD16 and HMGB1 and the protein expression of iNOS and CD16 were significantly decreased （P<0.01）. These effects were reversed by EX527 （P<0.05， P<0.01）. Furthermore， compared with the blank control group， the Aβ_25-35 group showed significantly increased cytoplasmic HMGB1 expression and p-p65/p65 ratio （P<0.01）， along with significantly decreased SIRT1 and nuclear HMGB1 expression （P<0.01）. In contrast， the S-AR group exhibited opposite trends compared with the Aβ_25-35 group， and the regulatory effects of S-AR on these proteins were reversed by EX527 （P<0.01）. ConclusionAR exerts neuroprotective effects in AD model rats by regulating microglial polarization and alleviating neuroinflammation， potentially through modulation of the SIRT1/HMGB1/NF-κB signaling pathway.

OBJECTIVE: To observe the clinical efficacy of heat-sensitive moxibustion robot for improving the depressive state of methamphetamine addicts during withdrawal period. METHODS: A total of 60 patients with methamphetamine addiction accompanied with depressive state were randomly divided into an observation group (40 cases, 4 cases dropped out) and a control group (20 cases, 2 cases dropped out). The control group received routine health education and addiction treatment in compulsory isolation drug rehabilitation center. On the basis of the treatment in the control group, in the observation group, the heat-sensitive moxibustion robot was used to locate sensitive points at the Shenque (CV8) and Danzhong (CV17), and dual-point sparrow-pecking moxibustion was delivered for 60 min per session. The moxibustion therapy was performed 4 times in the 1st week, 3 times in the 2nd and 3rd weeks respectively, and 2 times in the 4th week, for 12 times totally. The scores of Hamilton depression scale (HAMD), self-rating depression scale (SDS), visual analogue scale (VAS) for drug craving, Hamilton anxiety scale (HAMA), self-rating anxiety scale (SAS), and Pittsburgh sleep quality index (PSQI) were observed before treatment, at the end of the 2nd and 4th weeks of treatment, and 4 weeks after the treatment completion (follow-up) in the two groups. RESULTS: At each time point after treatment, in the observation group, the HAMD, VAS, HAMA and PSQI scores were decreased compared with those before treatment (P<0.01, P<0.001); at the end of the 4th week of treatment and in follow-up, the SDS and SAS scores were decreased compared with those before treatment (P<0.001, P<0.01). Compared before treatment, there were no significant differences in the above scores at each time point after treatment in the control group (P>0.05). In the observation group, at each time point after treatment, the HAMD and VAS scores were lower than those in the control group (P<0.01, P<0.001, P<0.05); at the end of the 4th week of treatment and in follow-up, the SDS and HAMA scores were lower than those in the control group (P<0.05, P<0.001); at the end of the 4th week of treatment, the PSQI score was lower than that in the control group (P<0.01). CONCLUSION Heat-sensitive moxibustion robot effectively improves depression, anxiety and sleep quality, and reduces drug craving in methamphetamine addicts during withdrawal period.
Humans ; Moxibustion/methods* ; Male ; Adult ; Female ; Methamphetamine/adverse effects* ; Depression/therapy* ; Middle Aged ; Robotics ; Young Adult ; Amphetamine-Related Disorders/psychology* ; Acupuncture Points ; Substance Withdrawal Syndrome/psychology*

This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

Objective:To explore the predictive value of ferritin combined with the COSSH-ACLF Ⅱ score for the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data of 419 cases with HBV-ACLF hospitalized at the Third Hospital of Hebei Medical University were retrospectively analyzed between January 1, 2013 and September 30, 2022, and were divided into the death ( n=127) and survival group ( n=292) according to the survival status of 28 days of follow-up. The Mann-Whitney U test was used to compare confirmation of non-normally distributed continuous data between two groups. The chi-square test was used for the comparison of numerical data between the two groups. Binary logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of HBV-ACLF patients. The predictive value of ferritin combined with the COSSH-ACLF Ⅱ score on the prognosis of HBV-ACLF was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC), net reclassification index (NRI), and comprehensive discriminant improvement index (IDI). Results:There were statistically significant differences in age, neutrophil count (NEUT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), serum creatinine (Scr), serum urea, prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), serum ferritin (SF), hepatic encephalopathy, and COSSH-ACLF Ⅱ scores between the two groups ( P<0.05). Ferritin ( OR=1.001, 95% CI:1.001-1.002, P<0.001) and COSSH-ACLF Ⅱ score ( OR=2.898, 95% CI:1.560-5.384, P<0.001) were independent factors for predicting short-term prognosis for patients with HBV-ACLF. Ferritin combined with COSSH-ACLF II score had a higher prognostic predictive value than ferritin (AUC=0.697, 95% CI: 0.651-0.741) and COSSH-ACLF II score (AUC=0.819, 95% CI: 0.779-0.855) for patients with HBV-ACLF (AUC=0.857, 95% CI: 0.819-0.889), with a statistically significant difference ( Z=6.287 and 2.666, respectively, P <0.05). The predictive effect was significantly improved following the addition of ferritin to the COSSH-ACLF Ⅱ score ( P<0.001), and the NRI and IDI were both >0 (NRI=0.144, 95% CI: 0.064-0.225; IDI=0.080, 95% CI: 0.052-0.108). Conclusion:Ferritin and COSSH-ACLF Ⅱ scores are independent factors that can predict short-term prognosis for patients with HBV-ACLF, and combing both has a higher predictive value.

To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

This article reported a case of autosomal dominant intellectual developmental disorder type 22 caused by a heterozygous mutation in the ZBTB18 gene. At 24 +4 weeks of gestation, prenatal ultrasound indicated a short outer diameter of the fetal corpus callosum and bilateral ventricular dilatation. Whole-genome copy number variation analysis of the fetus showed no abnormalities. Whole exome sequencing (WES) and Sanger sequencing validation of the family revealed the fetus carried a c.1374_1383del(p.S459*) heterozygous mutation in the ZBTB18 gene (NM_205768.3), which was neither phenotypically present nor genotypically detected in the parents, suggesting a de novo mutation. Based on the clinical manifestations, the fetus was diagnosed with autosomal dominant intellectual developmental disorder type 22. After genetic counseling, the pregnant woman opted for termination of the pregnancy. This case highlights the correlation between prenatal ultrasonic detection of callosal dysgenesis and lateral ventricular enlargement and intellectual developmental disorders caused by gene mutations. Furthermore, it expands the mutation spectrum of the ZBTB18 gene, thereby facilitating prenatal diagnosis and genetic counseling.

To investigate the mutations of NF1 and clinical phenotypes in patients with sporadic neurofibromatosis type 1 (NF1). This is aimed to evaluate the efficacy of high-throughput sequencing in diagnosing atypical cases, to expand the mutational spectrum of NF1, and to provide early diagnosis of NF1. Clinical data from 11 sporadic NF1 patients without family history treated at the Fifth Affiliated Hospital of Sun Yat-sen University (2019-2023) were collected. The mutations of NF1 gene were detected using whole-exome sequencing or chip-capture high-throughput sequencing, followed by bioinformatics analysis. Novel mutations were screened against normal population databases to exclude benign polymorphisms, and pathogenicity of the mutations was classified according to ACMG guidelines. The results showed that two novel frameshift mutations were identified: c.7904del (p.Asp2635Valfs*9) and c.5122_5123del (p.Phe1708Hisfs*9). The patient carrying c.7904del exhibited an undocumented phenotype of posterior medullary ischemic degeneration. Among the 11 NF1 patients, the types of mutations included frameshift (4/11), nonsense (3/11), intronic (2/11), splicing (1/11), and start codon variants (1/11). Common phenotypes were cafe-au-lait macules (8/11) and neurofibromas (6/11), yet significant phenotypic heterogeneity existed among patients sharing identical mutations. In conclusion, this study discovered two novel NF1 mutations and an unreported phenotype, expanding both the NF1 mutational spectra and highlights the need for attention to cerebrovascular status in patients carrying NF1 mutations. High-throughput sequencing significantly enhances molecular diagnostic efficacy for atypical NF1, providing a critical basis for clinical NF1 diagnosis.

Objective:To explore the predictive value of ferritin combined with the COSSH-ACLF Ⅱ score for the prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (HBV-ACLF).Methods:The clinical data of 419 cases with HBV-ACLF hospitalized at the Third Hospital of Hebei Medical University were retrospectively analyzed between January 1, 2013 and September 30, 2022, and were divided into the death ( n=127) and survival group ( n=292) according to the survival status of 28 days of follow-up. The Mann-Whitney U test was used to compare confirmation of non-normally distributed continuous data between two groups. The chi-square test was used for the comparison of numerical data between the two groups. Binary logistic regression analysis was used to analyze the independent risk factors affecting the prognosis of HBV-ACLF patients. The predictive value of ferritin combined with the COSSH-ACLF Ⅱ score on the prognosis of HBV-ACLF was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC), net reclassification index (NRI), and comprehensive discriminant improvement index (IDI). Results:There were statistically significant differences in age, neutrophil count (NEUT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), serum creatinine (Scr), serum urea, prothrombin time (PT), prothrombin activity (PTA), international normalized ratio (INR), serum ferritin (SF), hepatic encephalopathy, and COSSH-ACLF Ⅱ scores between the two groups ( P<0.05). Ferritin ( OR=1.001, 95% CI:1.001-1.002, P<0.001) and COSSH-ACLF Ⅱ score ( OR=2.898, 95% CI:1.560-5.384, P<0.001) were independent factors for predicting short-term prognosis for patients with HBV-ACLF. Ferritin combined with COSSH-ACLF II score had a higher prognostic predictive value than ferritin (AUC=0.697, 95% CI: 0.651-0.741) and COSSH-ACLF II score (AUC=0.819, 95% CI: 0.779-0.855) for patients with HBV-ACLF (AUC=0.857, 95% CI: 0.819-0.889), with a statistically significant difference ( Z=6.287 and 2.666, respectively, P <0.05). The predictive effect was significantly improved following the addition of ferritin to the COSSH-ACLF Ⅱ score ( P<0.001), and the NRI and IDI were both >0 (NRI=0.144, 95% CI: 0.064-0.225; IDI=0.080, 95% CI: 0.052-0.108). Conclusion:Ferritin and COSSH-ACLF Ⅱ scores are independent factors that can predict short-term prognosis for patients with HBV-ACLF, and combing both has a higher predictive value.

Objective:To analyze ultrasonographic manifestations and genetic etiology of nine fetuses with 7q11.23 duplication syndrome.Methods:Ultrasonographic finding, pregnancy outcome and follow-up of nine fetuses detected at the Prenatal Diagnosis Center of the Third Affiliated Hospital of Zhengzhou University from January 2017 to December 2021 were retrospectively analyzed.Results:The fetuses were found to harbor a duplication in the 7q11.23 region by chromosomal microarray analysis (CMA). Among these, five had shown ventriculomegaly, including four syndromic and one non-syndromic. For the remainders, one had ventricular septal defect and mild tricuspid regurgitation, one had echogenic intracardiac focus, whilst another two were normal. Five couples had accepted parental verification, and the results confirmed that the 7q11.23 duplication carried by their fetuses were de novo in origin. Following genetic counseling, seven couples had opted to terminate their pregnancies. Two fetuses were delivered at full term, and follow-up had found no abnormalities. Conclusion:Prenatal ultrasonographic manifestations of fetuses with 7q11.23 duplication syndrome are variable. CMA can provide assistance for their diagnosis and genetic counseling.

Objective:To explore the process and content of family management of asthma children and their caregivers, so as to provide basis for improving the health outcomes of asthma children.Methods:This study is qualitative research. From March to April 2022, 26 children and 26 main caregivers from the Asthma Clinic of the Children's Hospital affiliated to the Capital Institute of Pediatrics were selected by objective sampling for semi-structured interviews. QSR Nvivo 12 software and subject analysis method were used to analyze the data.Results:A total of 4 themes and 13 sub-themes were extracted, including the content on family management of asthma children (inducement prevention, drug management, disease monitoring), the family management style of asthma children (disease management concept, asthma management expectation, disease management life routine, disease essence understanding, disease management difficulty), and the family factors affecting the transition of family management of asthma children to self-management (promoting transition factors, obstructing transition factors), psychosocial state (numbness, optimism and stigma) .Conclusions:The family management of asthma children needs the intervention and support of professional nursing staff to improve the family management and the health outcomes of asthma children.