ObjectiveTo explore the relationship between acne vulgaris and gut microbiota. MethodsA total of 29 clinical cases diagnosed with moderate-to-severe acne vulgaris and 26 healthy individuals as control subjects were recruited. Fecal specimens were collected from all participants， and further analysis of gut microbial communities was performed by leveraging high-throughput sequencing techniques that target the hypervariable regions of 16S rRNA genes. ResultsAssociations between acne vulgaris and alterations in gut microbiota were identified. At the phylum level， the relative abundance of Bacteroidota exhibited a statistically significant elevation in the acne vulgaris cohort when compared with the healthy control group （P<0.01）， while Cyanobacteria was significantly lower in the acne group （P<0.01）. At the genus level， the top five different bacterial taxa in both groups were Bacteroides， Escherichia⁃Shigella， Klebsiella， Roseburia， and Parabacteroides. Among them， Bacteroides， Roseburia， and Parabacteroides were more abundant in acne patients. Linear discriminant analysis identified five biomarkers all belonging to the Bacteroidota phylum in the acne and control groups. These biomarkers belong to the phylum Bacteroidetes. ConclusionThere are significant differences in the composition of intestinal microbiota between acne patients and healthy people. Changes in the richness of specific bacterial genera may become new targets for the diagnosis and treatment of acne.

Objective To study the effect of Lishukang capsule on learning and memory impairment in mice with high altitude hypoxia based on Keap1/Nrf2/HO-1 signal pathway. Methods Sixty male Balb/C mice were randomly divided into normal control group, hypoxia model group, Rhodiola capsule group (400 mg/kg), low, medium and high dose groups of Lishukang capsule (400、 600、 800 mg/kg), with 10 mice in each group. The normal control group was fed at the local altitude (1 500 m) after 7 days of intragastric administration in each group, and the rest groups were fed at the low pressure and hypoxia animal experimental cabin to simulate the altitude of 7500 m for hypoxia for 3 days. During this period, the normal control group and the hypoxia model group were given normal saline once a day, and 1 hour after the last administration, the eight arm maze was used to test the spatial memory ability of mice under simulated high altitude hypoxia; HE staining was used to observe the morphological changes of hippocampus in mice; Western blot was used to detect the changes of protein content of Keap1/Nrf2/HO-1 signal pathway and apoptosis related protein in hippocampus of mice. Results Compared with the normal control group, the spatial memory ability of mice in the hypoxia model group was significantly impaired (P<0.01); HE staining showed that hippocampal neurons in mice were seriously injured; the content of brain tissue Keap1 protein and apoptosis related protein Bax and Caspase-3 increased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 decreased （P<0.01）. Compared with the hypoxia model group, the error rate of mice in the high dose group of Lishukang capsule in the eight arm maze behavior experiment was significantly reduced (P<0.05, P<0.01); HE staining showed that the neurons were arranged orderly and the cell morphology was good; the content of Keap1 protein and apoptosis related protein Bax and Caspase-3 decreased (P<0.01); the content of Nrf2, HO-1 and apoptosis related protein Bcl-2 increased（P<0.01）. Conclusion High altitude hypoxia can lead to oxidative stress injury in mice and induce the expression of apoptosis related genes, thus aggravating the cognitive dysfunction of mice; Lishukang capsule can effectively improve the learning and memory impairment in mice caused by hypoxia, and its mechanism may be related to regulating the Keap1/Nrf2/HO-1 signal pathway and reducing apoptosis.

Approximately 60% of colorectal cancer (CRC) patients exhibit TP53 mutations, which are strongly associated with tumor progression, chemotherapy resistance, and an unfavorable prognosis. However, targeting p53 has historically been challenging, and currently, there are no approved p53-based therapeutics for clinical use worldwide. In this study, we discovered that ubiquitin carboxyl terminal hydrolase L3 (UCHL3) plays a crucial role in high-level glycolysis, enhanced stem-like properties, and 5-fluorouracil (5-FU) chemoresistance in TP53-mutant CRC by exerting its deubiquitinating enzyme activity to stabilize α-enolase (ENO1) protein. Notably, we identified a newly Food and Drug Administration (FDA)-approved drug, pacritinib, that potently suppresses UCHL3 expression by blocking the janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) pathway in TP53-mutant CRC. Furthermore, Pacritinib was demonstrated to effectively inhibit glycolysis and improve the sensitivity to 5-FU chemotherapy in TP53-mutant CRC. Our findings suggest that targeting the JAK2-STAT3-UCHL3-ENO1 axis is a promising strategy to suppress glycolysis and enhance the efficacy of 5-FU chemotherapy in TP53-mutant CRC. Pacritinib shows potential for clinical application in the treatment of TP53-mutant CRC.

Objective:To provide molecular evidence for clinical diagnosis and genetic counseling by analyzing the clinical characteristics and identifying the pathogenic genes in a SPONASTRIME-type spondyloepimetaphyseal dysplasia(SEMDSP)family.Methods:Clinical data of the family members was collected and analyzed. Case 2 was identified as the proband for whole-exome sequencing and variant analysis. Suspected variants were validated across family numbers using Sanger sequencing.Results:The two affected individuals in this family, a brother and a sister, both presented as short stature. The initial diagnosis for the sister(case 1)was made at the age of 4 years and 2 months(height: 88.6 cm), and for the brother(case 2)at 4 years and 4 months(height: 81.6 cm). Both individuals exhibited distinctive facial features, including frontal bossing, midface hypoplasia with depressed nasal bridge, upturned nostrils, ocular hypertelorism, and epicanthus, thick hair, short lingual frenulum, stubby fingers and palms, and absence of scoliosis. The parents displayed normal phenotypes. Laboratory tests indicated growth hormone deficiency in both affected individuals. Imaging studies revealed significant bone age delay in case 2, while case 1 showed longitudinal striations at the distal radius but with bone age matching their actual age(5 years and 11 months). Despite receiving recombinant human growth hormone treatment, both patients had inadequate responses. Genetic testing identified compound heterozygous mutations in the TONSL gene shared by the two siblings. These mutations included a paternally inherited c. 1291-14_1291-11delCCTC and a maternally inherited c. 1909_1920delACGCTGCAGCAG. Notably, SEMDSP families have not been reported in China, and the c. 1909_1920delACGCTGCAGCAG mutation is a novel variant.Conclusion:Two patients were diagnosed as spondyloepimetaphyseal dysplasia, SPONASTRIME type, and the compound heterozygous variant was the genetic cause of this family.

OBJECTIVE: To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM). METHODS: Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members. RESULTS: The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c.314T>G (p.L105R) variant of the INS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines. CONCLUSION The c.314T>G (P.L105R) variant of the INS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.
Humans ; Infant ; Child ; Infant, Newborn ; Female ; Mutation ; Insulin/genetics* ; Diabetes Mellitus/genetics* ; Genetic Testing

Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.

Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.

Starvation therapy is an emerging oncological treatment that targets the abnormally elevated nutrient uptake and metabolic pathways to inhibit and kill tumors. In addition to glucose, the targets of starvation therapy also include other nutrients in tumor cells.However, concerns like ineffective targeting and drug tolerance probably have an impact on their clinical translation.Nanomaterial-assisted starvation treatment has been developing quickly in recent years to address these concerns.In this review, several exemplary nanomedicines for starvation therapy and combined starvation therapy with other therapies were offered.They target nutrients other than glucose metabolism, including lactic acid, amino acids, and lipids, using nanomaterials to improve the efficacy of starvation therapy.This review provides reference for further development of nanomedicines with starvation treatment effect.

Objective To provide a scientific basis for the formulation of effective incentive measures for rural health workers,by analyzing the factors influencing their work enthusiasm and constructing an incentive mechanism framework.Methods A field questionnaire survey and personal in-depth interview were conducted on 803 health technicians from 45 township health centers in Shandong,Anhui and Shanxi provinces.The study covered economic,management,education and career supports aspects,and the data were analyzed in descriptive,multi-level model and correlation analyses.Results The work enthusiasm scoring of rural health workers was 89.83 + 9.54.Workload,doctor-patient relationship,work competence and income index were the four influencing factors,with the differences showing statistical significance(P ＜0.05).The income index (income expectancy/real income affects work) influences the enthusiasm negatively,while the rest of the factors were positive.Work enthusiasm was positively correlated with three dimensions of job performance.The satisfaction of interpersonal relationship,workload and competence were positively correlated with work enthusiasm.The correlation indexes are respectively 0.35,0.33 and 0.21 (P ＜ 0.01).Conclusions To motivate primary health institutions and their health workers,the authorities should focus on the economic factors,and take into account non-economic ones,while improving the performance-based wage system and creating a fair workplace culture.

Simulations can mimic the environment that refers to the surgery operation to improve the technical skills of the trainees. In this paper, we designed a new cardiac surgery simulative training system. The isolated pig heart was selected as the heart model. A mechanical device was designed to achieve the beating of heart model. At the same time, adjusting frequencies of mechanical movement could change the rating of heartbeat. In order to validate the rationality of the system, 12 non-medical specialty students and 12 medical specialty students were divided into two groups, which consecutively accepted seven-days of training for off-pump coronary artery bypass grafting using the cardiac surgery simulative training system. The time for completing bypass grafting before and after training were recorded. And the bridging outcomes of each trainee were assessed by 3 surgery cardiac surgeons using the object structured assessments of technical skill (OSATS) criteria. After training, each trainee could finish the bypass suturing in a shorter time than before training, and the scores of each trainee assessed by OSATS criteria were also improved. The results showed that the cardiac surgery simulative training system had better training effect in improving the surgical techniques, operation skills and proficiency of surgical instruments of trainees.