Objective To mine temozolomide-related adverse drug event(ADE)signals in the real world and to provide a reference for the safe clinical use of temozolomide.Methods The U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)was used to collect the ADE reporting data of temozolomide in the FAERS database from January 1,2004 to December 31,2022.The signal mining was performed using the report ratio method and Bayesian confidence interval progressive neural network method to analyze the occurrence of ADE.Results In the database,there were 24 725 ADE reports with temozolomide as the primary suspected drug,and a total of 300 ADE signals were identified,involving 23 system organ categories,and the top 5 were blood and lymphatic system diseases,systemic diseases and various reactions of administration sites,various examinations,various neurological diseases,various injuries,poisoning and procedural complications etc.the most frequently reported ADE signals included thrombocytopenia,low platelet count,neutral granulocytopenia,pancytopenia,convulsive attacks,and febrile neutropenia.42 new suspected adverse reactions were discovered,which were not recorded in the instructions,such as pseudomonas skin infection,herpetic meningoencephalitis,hypoglossal nerve paralysis,porokeratosis,etc.Conclusion The common adverse reactions of temozolomide in the real world are generally consistent with the instructions,but some new suspicious adverse reactions have been discovered.During clinical drug use,special attention should be paid to these new adverse reactions,and it is recommended to monitor patients'adverse reactions and take appropriate measures in a timely manner.

Objective:To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease.Methods:A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children′s Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children′s Hospital (No. KYSQ2022-263).Results:The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c. 1103_1104delAG (p.Gln368Argfs*8) and c. 1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c. 1103_1104delAG was predicted as a pathogenic variant (PVS1+ PM2_Supporting+ PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+ PM3+ PM2_Supporting+ PP4). Conclusion:The c. 1103_1104delAG and c. 1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

Objective To analyze the correlation between T lymphocyte subsets,neutrophil/lymphocyte ratio(NLR),procalcitonin(PCT)and the severity of sepsis.Methods A prospective research method was adopted.A total of 78 sepsis patients admitted to the department of intensive care medicine of Zibo Central Hospital from January 2021 to December 2022 were selected as the research subjects.Patients were divided into a septic shock group(37 cases)and a sepsis group(41 cases)based on the severity of their condition,with 40 healthy examinees from our hospital as the healthy control group.Using flow cytometry to measure the levels of CD4+ T lymphocytes count(CD4+ T)and CD8+ T lymphocytes count(CD8+ T)in three groups of subjects,calculate the CD4+ T/CD8+ T lymphocyte ratio(CD4+ T/CD8+ T)and NLR.The levels of PCT and interleukin-6(IL-6)were measured using electrochemiluminescence immunoassay,and the levels of C-reactive protein(CRP)were measured using immunoassay turbidimetry.Acute physiology and chronic health evaluationⅡ(APACHEⅡ)score within 24 hours was recorded for the two groups of patients,and the differences in lymphocyte subsets and various inflammatory indicators were compared between the groups.Pearson correlation analysis was used to analyze the correlation between various indicators and APACHEⅡscore.Results The CD4+ T,CD8+ T,and CD4+T/CD8+T levels in the septic shock and sepsis groups were significantly lower than those in the healthy control group[CD4+ T(×106/L):168.27±76.68,266.08±131.57 vs.789.60±173.78,CD8+ T(×106/L):156.50±68.37,205.81±75.60 vs.636.42±90.59,CD4+ T/CD8+ T:1.09±0.39,1.27±0.34 vs.1.44±0.38,all P<0.01],NLR,PCT,CRP and IL-6 were significantly higher than those in the healthy control group[NLR:25.85±11.62,15.94±8.72 vs.2.68±1.31,PCT(μg/L):21.82±15.28,9.09±4.96 vs.0.13±0.10,CRP(mg/L):158.65±62.33,106.97±51.49 vs.6.48±2.08,IL-6(ng/L):1 344.64±899.21,245.31±176.99 vs.3.25±1.83,all P<0.01].The APACHEⅡscore in the septic shock group was significantly higher than that in the sepsis group(32.00±1.00 vs.22.01±1.09,P<0.05).Correlation analysis showed that the levels of CD4+ T,CD8+ T,CD4+ T/CD8+ T in two groups of sepsis patients were negatively correlated with the APACHEⅡscore(r values were-0.571,-0.506,and-0.555,respectively,all P<0.01),while the levels of NLR,PCT,CRP,and IL-6 were positively correlated with the APACHEⅡscore(r values were 0.711,0.709,0.777,and 0.707,respectively,all P<0.01).Conclusions As the levels of T lymphocyte subsets decrease,inflammatory indicators like NLR and PCT rise,indicating a more severe sepsis condition.Therefore,T lymphocyte subsets and levels of various inflammatory indicators can serve as markers for evaluating the severity of sepsis.

Objective:To explore the application effect of integrated Chinese and Western medicine nursing based on the individual and family self-management theory (IFSMT) in patients with urinary incontinence after stroke, and provide reference for clinical nurses to effectively rehabilitate these patients.Methods:This was a quasi-experimental study. A total of 136 patients with urinary incontinence after stroke who were hospitalized in the Department of Encephalopathy of Shanxi Acupuncture and Moxibology Hospital from February 2022 to May 2023 were selected as the study objects by convenience sampling method. The subjects were divided into the control group and the experimental group with 68 cases in each group by random number table method. The control group received routine rehabilitation nursing, and the experimental group received integrated Chinese and western medicine nursing based on IFSMT on the basis of routine rehabilitation nursing. Urinary status, activities of daily living and quality of life of 2 groups were compared.Results:Ultimately, there were 68 cases were admitted in each group. In the control group, male 45 cases, female 23 cases, aged (62.35 ± 4.94) years old. In the experimental group, male 49 cases, female 19 cases, aged (61.94 ± 5.02) years old. There was no statistical significance in urinary status, activities of daily living and quality of life scores between the 2 groups before the intervention (all P>0.05). After the intervention, the average daily urination frequency of experimental group was (7.94 ± 1.08) times, which was lower than that of control group (9.88 ± 1.09) times; the average daily frequency of incontinence in the experimental group was (3.63 ± 1.65) times, lower than (5.03 ± 3.35)times in the control group; the average daily urine volume of experimental group was (107.34 ± 4.15) ml, higher than (89.62 ± 19.71) ml of control group, and the differences were statistically significant ( t=10.46,3.09, -7.23, all P<0.05). The scores of activities of daily living in the experimental group was (60.44 ± 3.65) points, which were higher than (46.24 ± 3.29) points in the control group; the Incontinence Quality of Life Questionnaire score of experimental group was (80.38 ± 4.65) points, which was higher than (64.62 ± 5.62) points of control group; Insomnia Severity Index-Short Form score of the experimental group was (10.94 ± 5.17) points, which was lower than (12.85 ± 4.30) points of the control group, and the differences were statistically significant ( t=23.85, -17.86, 2.34, all P<0.05). Conclusions:Integrated Chinese and western medicine nursing intervention based on IFSMT has a positive effect on patients with urinary incontinence after stroke, and can significantly improve patients' urination and daily living activities, thus improving patients' quality of life.

In this study, 34 deep eutectic solvents (DESs) were successfully prepared for the extraction of proanthocyanidin from Rhodiolae Crenulatae Radix et Rhizomes. The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis. The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30% (V/V) in DESs. AB-8 macroporous resin and ethyl acetate were used for separation and refining, and the oligomer-rich proanthocyanidin components were eventually obtained. The ultraviolet (UV) and infrared (IR) spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin. To further clarify the chemical composition of proanthocyanidin, an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins structural library and mass defect filtering (MDF) algorithm, combined with the full mass spectrometry (MS)/dd-MS² scan mode that turns on the "if idle pick others" function. By using ultra-high performance liquid chromatography and high-resolution MS (UHPLC/HRMS), the analysis used both targeted and non-targeted methods to detect proanthocyanidins. Finally, 50 oligomeric proanthocyanidin (OPC) compounds were identified, including 7 monomers, 22 dimers, 20 trimers, and 1 tetramer, most of which were procyanidins of proanthocyanidins (84%), and a small amount of prodelphinidin (14%) and other types of proanthocyanidins (2%), which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes. Meanwhile, the comparison with the grape seeds OPCs standard (United States Pharmacopeia) revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant, suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost, sustainability, and tissue targeting. Thus, they hold promise for disease treatment and drug delivery. In this study, we proposed a time-efficient method, PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles (GDNVs). Subsequently, curcumin (CUR) was loaded onto GDNV by ultrasonic incubation. The optimum conditions for ginger-derived nanovesicles loaded with curcumin (CG) were ultrasound time of 3 min, a carrier-to-drug ratio (GDNV:CUR) of 1:1. The study achieved a high loading capacity (94.027% ± 0.094%) and encapsulation efficiency (89.300% ± 0.344%). Finally, the drugs' in vivo distribution and anti-colitis activity were investigated in mice. CG was primarily distributed in the colon after oral administration. Compared to CUR and GDNV, CG was superior in improving disease activity, colon length, liver and spleen coefficients, myeloperoxidase activity, and biochemical factor levels in ulcerative colitis (UC) mice. In addition, CG plays a protective role against UC by modulating serum metabolite levels and gut flora. In summary, our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

In this study,34 deep eutectic solvents(DESs)were successfully prepared for the extraction of proan-thocyanidin from Rhodiolae Crenulatae Radix et Rhizomes.The extraction process was optimized using single factor exploration and Box-Behnken design-response surface analysis.The extraction rate was significantly improved when the molar ratio of choline chloride to 1,3-propanediol was 1:3.5 and the water content was 30％(V/V)in DESs.AB-8 macroporous resin and ethyl acetate were used for separation and refining,and the oligomer-rich proanthocyanidin components were eventually obtained.The ultra-violet(UV)and infrared(IR)spectra showed that the proanthocyanidins were mainly composed of catechin and epicatechin.To further clarify the chemical composition of proanthocyanidin,an ion scan list containing 156 proanthocyanidins precursors was obtained by constructing a proanthocyanidins struc-tural library and mass defect filtering(MDF)algorithm,combined with the full mass spectrometry(MS)/dd-MS2 scan mode that turns on the"if idle pick others"function.By using ultra-high performance liquid chromatography and high-resolution MS(UHPLC/HRMS),the analysis used both targeted and non-targeted methods to detect proanthocyanidins.Finally,50 oligomeric proanthocyanidin(OPC)com-pounds were identified,including 7 monomers,22 dimers,20 trimers,and 1 tetramer,most of which were procyanidins of proanthocyanidins(84％),and a small amount of prodelphinidin(14％)and other types of proanthocyanidins(2％),which enabled the systematic characterization of proanthocyanidin components from Rhodiolae Crenulatae Radix et Rhizomes.Meanwhile,the comparison with the grape seeds OPCs standard(United States Pharmacopeia)revealed that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes were more abundant,suggesting that the proanthocyanidins in Rhodiolae Crenulatae Radix et Rhizomes has promising applications.

Plant-derived nanovesicles have gained attention given their similarity to mammalian exosomes and advantages such as low cost,sustainability,and tissue targeting.Thus,they hold promise for disease treatment and drug delivery.In this study,we proposed a time-efficient method,PEG 8000 combined with sucrose density gradient centrifugation to prepare ginger-derived nanovesicles(GDNVs).Subse-quently,curcumin(CUR)was loaded onto GDNV by ultrasonic incubation.The optimum conditions for ginger-derived nanovesicles loaded with curcumin(CG)were ultrasound time of 3 min,a carrier-to-drug ratio(GDNV:CUR)of 1∶1.The study achieved a high loading capacity(94.027％±0.094％)and encapsu-lation efficiency(89.300％±0.344％).Finally,the drugs'in vivo distribution and anti-colitis activity were investigated in mice.CG was primarily distributed in the colon after oral administration.Compared to CUR and GDNV,CG was superior in improving disease activity,colon length,liver and spleen coefficients,myeloperoxidase activity,and biochemical factor levels in ulcerative colitis(UC)mice.In addition,CG plays a protective role against UC by modulating serum metabolite levels and gut flora.In summary,our study demonstrated that GDNV can be used for CUR delivery with enhanced therapeutic potential.

OBJECTIVE: To explore the clinical characteristics and genetic etiology of a child with Spondyloocular syndrome (SOS) in order to enhance the awareness and understanding of this disease. METHODS: A 3.5-year-old boy with SOS who had presented at the Department of Medical Genetics of Hunan Children's Hospital on August 10, 2023 due to the repeated fractures for over 2 years and after binocular cataract surgery was selected as the study subject. Clinical data of his pedigree were collected, and peripheral venous blood samples were collected for the extraction of genomic DNA and subjected to trio-whole exome sequencing. Candidate variants were verified by Sanger sequencing and analyzed with bioinformatic software. This study was approved by the Medical Ethics Committee of Hunan Children's Hospital (Ethics No. KYAQ2022-263). RESULTS: The child had manifested repeated fractures, bilateral bowed femur, osteoporosis, cataract, atrial septal defect, and developmental delay. Ultrasonography has revealed fetal edema, peritoneal effusion, pleural effusion and polyhydramnios. Trio-whole exome sequencing and Sanger sequencing revealed that he has harbored compound heterozygous variants of the XYLT2 gene, namely c.1103_1104delAG (p.Gln368Argfs*8) and c.1238_1253delinsA (p.Val413_Pro418delinsGlu), which were inherited from his phenotypically normal father and mother, respectively. Neither variant was reported previously. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and recommendations from the Clinical Genome Resource (ClinGen), the c.1103_1104delAG was predicted as a pathogenic variant (PVS1+PM2_Supporting+PP4), whilst the c.1238_1253delinsA was predicted as a likely pathogenic variant (PM4+PM3+PM2_Supporting+PP4). CONCLUSION The c.1103_1104delAG and c.1238_1253delinsA compound heterozygous variants of the XYLT2 gene probably underlay the pathogenesis in this child. Above finding has enriched the phenotypic and mutational spectrum of SOS, and provided a basis for the clinical diagnosis, treatment, prognosis assessment and genetic counseling for this pedigree.
Humans ; Male ; Child, Preschool ; Heterozygote ; Pentosyltransferases/genetics* ; Pedigree ; UDP Xylose-Protein Xylosyltransferase ; Mutation ; Exome Sequencing ; Genetic Testing