ObjectiveTo study the effect of Taikong Yangxin Pills on the metabolism of simulated weightless rats based on metabolomics and discuss the metabolism mechanism. MethodsIn the simulated space capsule environment on the ground， the rat model of simulated weightlessness was established by the tail suspension method. Rats were randomly grouped as follows： out-of-capsule control， in-capsule control， model， and high （3.0 g·kg^-1） and low （1.5 g·kg^-1） doses of Taikong Yangxin Pills， and they were administrated with corresponding drugs by gavage for 28 days. The serum levels of endogenous metabolites in rats were determined by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF/MS）. The obtained data were processed by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） to screen for differential metabolites and potential biomarkers. MetaboAnalyst 5.0 was used for pathway enrichment analysis to explain the metabolic regulation mechanism of the drug. ResultsCompared with the out-of-capsule control group， the in-capsule control group showed elevated levels of thirteen metabolites， including 14-hydroxyhexadecanoic acid， linoleic acid， and α-linolenic acid （P<0.05）， which suggested that the space capsule environment mainly affected the metabolism of α-linolenic acid and linoleic acid in the rats. Compared with the in-capsule control group， the model group showed lowered levels of fourteen metabolites， including 4-imidazolone-5-propionic acid， isocitric acid/citric acid， and L-tyrosine （P<0.05）， which were recovered after the treatment with Taikong Yangxin pills （P<0.05）. The pathway enrichment analysis revealed that weightlessness induced by tail suspension and drug intervention mainly involved the phenylalanine， tyrosine， and tryptophan biosynthesis， tyrosine metabolism， histidine metabolism， and citric acid cycle. ConclusionThe simulated space capsule environment and simulated weightlessness induced by tail suspension can both affect the metabolism level of rats. Taikong Yangxin pills can ameliorate the metabolic abnormality in the rat model of weightlessness by regulating various amino acids and energy metabolism-related pathways.

Ethical utilitarianism is a consequence-oriented ethical theory that pursues the maximization of happiness and fully considers the long-term impact of behavior. In the ethical review of human organ donation and transplantation, this theory is mainly applied in three aspects, ethical review supervision, process and content. However, in practice, it faces challenges such as the difficulty and subjectivity of utility calculation, the balance between individual rights and social welfare, the long-term impact of decision-making, and international cooperation under a global perspective. Therefore, governance strategies such as improving ethical review policy rules, refining the ethical review system by drawing on international experience, and strengthening public education and publicity are proposed. Despite many challenges, ethical utilitarianism still provides an important theoretical framework for the ethical review of human organ donation and transplantation. Therefore, this article reviews the application of ethical utilitarianism in the ethical review of human organ donation and transplantation and its challenges, aiming to provide a reference for related research on the ethical review of human organ donation and transplantation.

Objective To analyze the effect of hand transmitted vibration on fingertip thermotactile perception threshold (TPT) among grinding workers in a sports equipment manufacturing enterprise. Methods A total of 151 male grinding workers from a sports equipment manufacturing enterprise in Guangdong Province were enrolled in the vibration exposure group, and 51 male workers without hand-transmitted vibration exposure were enrolled in the control group, using the judgment sampling method. Basic health conditions of the workers were surveyed in both groups. The TPTs of the distal phalanges of the index and little fingers on both hands were tested using an HVLab thermal perception tester. Results The detection rates of finger numbness and tingling among workers in the vibration exposure group were higher than those in the control group (92.1% vs 7.8% and 59.6% vs 0.0%, respectively, both P<0.01). The detection rates of numbness or tingling of different fingers in the vibration exposure group descended in the following order: index finger, middle finger, ring finger, thumb and little finger. The hot threshold of the index finger and little finger increased (all P<0.01), while the cold threshold decreased (all P<0.01) in the vibration exposure group, compared with the control group. The results of generalized linear regression analysis showed that with the increase of the duration of hand-transmitted vibration, the hot threshold of the index finger and the little finger of both hands increased (all P<0.01), and the cold threshold decreased (all P<0.01). The hot thresholds of workers with numbness of both the index fingers and left little finger were higher than those of workers without numbness of the same finger (all P<0.05). The hot threshold of workers with tingling of the left index finger was higher than those without tingling (P<0.05). The cold thresholds of workers with tingling of the both index fingers and left little finger were lower than those without tingling of the same finger (all P<0.05). The hot threshold of the right little finger increased with age (P<0.01), while the cold thresholds of both little fingers decreased with age (all P<0.01). Conclusion Hand-transmitted vibration exposure increases fingertip hot threshold and decreases fingertip cold threshold of workers exposed to hand-transmitted vibration. Years of service in hand-transmitted vibration work, finger numbness or tingling, and age were influencing factors of TPT. Fingertip TPT examination can be used to assist in the early detection of vibration-induced nerve injury in workers exposed to hand-transmitted vibration.

OBJECTIVE: To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband. METHODS: Chinese pedigree which opted elective abortion at the Women and Children's Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). RESULTS: Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c.7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c.1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. CONCLUSION This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.
Female ; Humans ; Pregnancy ; Abnormalities, Multiple/genetics* ; Antigens, Neoplasm/genetics* ; Cell Cycle Proteins/genetics* ; Cerebellum/abnormalities* ; Cytoskeletal Proteins/genetics* ; Eye Abnormalities/genetics* ; Introns/genetics* ; Kidney Diseases, Cystic/diagnosis* ; Pedigree ; Retina/abnormalities* ; Sequence Analysis, RNA/methods* ; Whole Genome Sequencing/methods* ; Child

The study aims to investigate the effects of adding different proportions of Codonopsis radix compound crude extracts to the rabbit diet on growth performance,immune status,intesti-nal enzyme activity,structure,and microbial composition.A total of 96 5-week-old New Zealand White rabbits were randomly divided into 4 groups,with 6 replicates per group.The control group(BC)was fed a basal diet,while the experimental groups(CM-H and CM-L)were fed a basal diet supplemented with 1 000 mg/kg and 500 mg/kg of Codonopsis radix compound crude extracts,re-spectively.The antibiotic group(CK)was fed a basal diet supplemented with 300 mg/kg of keto-tifen.The experimental period was 42 days.Blood samples were collected at days 21 and 42,and se-rum biochemical and immune markers were determined.Intestinal segments and contents were col-lected at day 42 for analysis of intestinal health.The results showed that compared with the BC group,the average daily gain,feed-to-gain ratio,and diarrhea rate were significantly higher(P＜0.05)in the CM-H and CM-L groups.The total cholesterol(Tchol)content in the serum was sig-nificantly lower in the CM-H group at day 21 and the CM-L group at day 42(P＜0.05).The high-density lipoprotein(HDL)was significantly higher in the CM-H and CM-L groups than in the CK group at day 42(P＜0.05),and the total protein(TP)in the serum was significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).The IgG and IgM levels in the serum were significantly higher in the CM-H and CM-L groups than in the BC group(P＜0.05).In the CM-H and CM-L groups,the content of acetic acid in the colon was significantly higher than that in the BC group(P＜0.05).The content of propionic acid in the colon of the CM-L group was also significantly higher than that in the BC group(P＜0.05).The content of α-amylase in the duode-num,the content of trypsin in the duodenum,the pancreas,and the ileum of the CM-H group were significantly higher than those in the BC group(P＜0.05),and the content of trypsin in the duode-num of the CM-H group was significantly higher than those in the BC group and the CM-L group(P＜0.05).Compared with the BC group,the content of GPX1 in the ileum and jejunum of the CM-L group and the ileum of the CM-H group was significantly increased(P＜0.05),and the length of the villi in the duodenum of the CM-H group was significantly increased(P＜0.05).Compared with the BC group,the expression level of ZO-1 in the ileum of the CM-H group was significantly upregulated(P＜0.05),and the expression level of Claudin in the jejunum of the CM-H group and the CM-L group was significantly higher than that in the CK group(P＜0.05).The high-throughput sequencing results showed that the Sob index was significantly higher in the CM-L group compared to the BC group(P＜0.05).At the phylum level,the Firmicutes and Bacteroid-ota phyla were the main phyla.At the genus level,Akkermansia and Ruminococcus were the main genera.The relative abundance of Papillibacter and Eubacterium_ruminantium_group in the CM-L group was significantly higher than that in the CK group(P＜0.05).In summary,adding a Codonopsis radix compound crude extract to the diet can improve the growth performance,immu-nity,antioxidant capacity,integrity of intestinal mucosal structure,enzyme activity in the intestine,and increase the diversity of microorganisms in the blind intestine when the diet is supplemented with 500 mg/kg of Codonopsis radix compound crude extract.

Objective:To discuss the causal association between sterol esters and intrahepatic duct,biliary tract,and gallbladder malignancies using two-sample Mendelian randomization(MR)analysis,and to clarify the biological mechanisms of sterol esters,and to provide the a basis for early prevention and treatment of these malignancies.Methods:The instrumental variable data for 15 different types of sterol ester traits were obtained from the Finnish database(FinnGen).The genome-wide association study(GWAS)data for intrahepatic duct,biliary tract,and gallbladder malignancies were retrieved from the GWAS database using the keywords"sterol ester"and"intrahepatic duct,biliary tract,and gallbladder malignancies"(accession numbers:ICD-O-3 and GCST90277238-GCST9027725).The inverse-variance weighted(IVW)method,MR-Egger regression,and weighted median(WM)method were used to assess the causal association between sterol esters and the risk of these malignancies.Pleiotropy was tested using the MR-Egger intercept method;heterogeneity was evaluated using Cochran's Q test;and sensitivity analysis was performed using the leave-one-out approach to comprehensively assess the reliability and robustness of the results.Results:The IVW analysis results showed that Sterol ester(27:1/14:0)odds ratio(OR)=2.349,95%confidence interval(CI)=1.371-4.025,P=0.002),Sterol ester(27:1/16:0)(OR=1.248,95%CI=1.018-1.523,P=0.033),Sterol ester(27:1/18:2)(OR=1.361,95%CI=1.078-1.718,P=0.009),and Sterol ester(27:1/22:6)(OR=1.339,95%CI=1.001-1.791,P=0.049)were associated with an increased risk of intrahepatic duct,biliary tract,and gallbladder malignancies.The MR-Egger regression analysis results indicated that Sterol ester(27:1/18:2)(OR=2.038,95%CI=1.337-3.105,P=0.011)was a risk factor for these malignancies.The WM analysis results revealed that Sterol ester(27:1/14:0)(OR=2.786,95%CI=1.419-5.468,P=0.003)and Sterol ester(27:1/18:2)(OR=1.548,95%CI=1.148-2.088,P=0.004)were also risk factors.The MR-Egger intercept analysis and Cochran's Q test results indicated no significant horizontal pleiotropy or heterogeneity.The leave-one-out sensitivity analysis did not identify any influential outlier single nucleotide polymorphism(SNPs),confirming the reliability of the study.Conclusion:Sterol ester(27:1/14:0),Sterol ester(27:1/16:0),Sterol ester(27:1/18:2),and Sterol ester(27:1/22:6)exhibit causal associations with intrahepatic duct,biliary tract,and gallbladder malignancies and may promote their development.

Objective:To investigate the efficacy and safety of glofitamab in the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL).Methods:A retrospective case series study was performed. The clinical data of 11 patients with relapsed/refractory DLBCL who were treated with glofitamab in Sichuan Provincial People's Hospital from March 2024 to October 2024 were retrospectively analyzed. All patients received glofitamab monotherapy. Dose escalation was required in the first course, and glofitamab at a dose of 30 mg was administered from the second to the 12th course. The general data, clinical manifestations, laboratory examination results, Eastern Cooperative Oncology Group (ECOG) performance score, previous treatment history, therapeutic effect after medication and adverse reactions were collected.Results:Among 11 patients, there were 8 males and 3 females, with the median age [ M ( Q1, Q3)] of 60 (51, 76) years; 1 case was primary central nervous system DLBCL. The median number of prior treatment lines was 3 (2, 3) lines, and 6 cases received ≥3 lines of therapy; 1 case was double DLBCL and 3 cases was complicated with p53 mutations. The median follow-up time was 5 months (2-7 months). After treatment of the median number of glofitamab, 3 cases achieved complete remission, among which 1 case successfully bridged to autologous hematopoietic stem cell transplantation; 1 case had the stable disease and 7 cases achieved partial remission. Grade 1-2 adverse events included mild leukopenia in 3 patients, mild anemia in 4 patients, thrombocytopenia in 1 patient, and lymphopenia in 8 patients. Grade 3 hematologic adverse events included thrombocytopenia in 1 patient and severe lymphopenia in 1 patient. Non-hematological toxicities included mild rash in 1 patient, grade 1 liver dysfunction in 3 patients and inflammatory factor storm in 4 patients. No medication stop or deferral was found in patients due to severe adverse events. Conclusions:Glofitamab demonstrates a high response rate in the treatment of relapsed/refractory DLBCL, with manageable adverse events and a favorable safety.

Objective:To explore the genetic etiology of a Chinese pedigree with recurrent Joubert syndrome with negative results by whole-exome sequencing in the prior proband.Methods:A Chinese pedigree which opted elective abortion at the Women and Children′s Hospital Affiliated to Chongqing Medical University in December 2024 was selected as the study subject. Whole-genome sequencing was carried out on fetal tissue after termination of pregnancy. Candidate variants were validated by Sanger sequencing and interpreted, while non-coding variant was analyzed using in silico prediction tools. RNA sequencing and cDNA sequencing were conducted on fetal brain tissue. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.2024YL045-02). Results:Both the fetus and the affected child were found to harbor compound heterozygous variants of the CEP290 gene, namely c. 7341dup (p.Leu2448fs*8) (pathogenic, maternally inherited) and c. 1523-408G>A (likely pathogenic, paternally inherited). Both in silico analysis and fetal brain RNA sequencing confirmed aberrant RNA splicing caused by the intronic variant. Conclusion:This case has highlighted the value of combining whole-genome sequencing with RNA functional validation. Above results not only enriched the spectrum of CEP290 gene mutations but also underscored its diagnostic value in resolving complex prenatal cases, providing critical clues for the prenatal diagnosis and recurrence risk assessment in genetic counseling.

ObjectiveTo investigate the clinical features and outcomes of recompensation in patients with autoimmune hepatitis （AIH）-related decompensated cirrhosis， to identify independent predictive factors， and to construct a nomogram prediction model for the probability of recompensation. MethodsA retrospective cohort study was conducted among the adult patients with AIH-related decompensated cirrhosis who were admitted to The Fifth Medical Center of PLA General Hospital from January 2015 to August 2023 （n=211）. The primary endpoint was achievement of recompensation， and the secondary endpoint was liver-related death or liver transplantation. According to the outcome of the patients at the end of the follow-up， the patients were divided into the recompensation group （n=16） and the persistent decompensation group（n=150）.The independent-samples t test was used for comparison of normally distributed continuous data with homogeneity of variance， and the Mann-Whitney U rank sum test was used for comparison of non-normally distributed continuous data with heterogeneity of variance； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups； the Kaplan-Meier method was used for survival analysis； the Cox proportional-hazards regression model was used to identify independent predictive factors， and a nomogram model was constructed and validated. ResultsA total of 211 patients were enrolled， with a median age of 55.0 years and a median follow-up time of 44.0 months， and female patients accounted for 87.2%. Among the 211 patients， 61 （with a cumulative proportion of 35.5%） achieved recompensation. Compared with the persistent decompensation group， the recompensation group had significantly higher white blood cell count， platelet count （PLT）， total bilirubin （TBil）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， total bile acid， prothrombin time， international normalized ratio （INR）， SMA positive rate， Model for End-Stage Liver Disease （MELD） score， Child-Pugh score， and rate of use of glucocorticoids （all P0.05）， as well as significantly lower age at baseline， number of complications， and death/liver transplantation rate （all P0.05）. At 3 and 12 months after treatment， the recompensation group had continuous improvements in AST， TBil， INR， IgG， MELD score， and Child-Pugh score， which were significantly lower than the values in the persistent decompensation group （all P0.05）， alongside with continuous increases in PLT and albumin， which were significantly higher than the values in the persistent decompensation group （P0.05）. The multivariate Cox regression analysis showed that baseline ALT （hazard ratio ［HR］=1.067， 95% confidence interval ［CI］： 1.010 — 1.127， P=0.021）， IgG （HR=0.463，95%CI：0.258 — 0.833， P=0.010）， SMA positivity （HR=3.122，95%CI：1.768 — 5.515， P0.001）， and glucocorticoid therapy （HR=20.651，95%CI：8.744 — 48.770， P0.001） were independent predictive factors for recompensation， and the nomogram model based on these predictive factors showed excellent predictive performance （C-index=0.87，95%CI：0.84 — 0.90）. ConclusionAchieving recompensation significantly improves clinical outcomes in patients with AIH-related decompensated cirrhosis. Baseline SMA positivity， a high level of ALT， a low level of IgG， and corticosteroid therapy are independent predictive factors for recompensation. The predictive model constructed based on these factors can provide a basis for decision-making in individualized clinical management.

Objective To investigate the correlation between cognitive impairment of cerebral small vessel disease(CSVD)and white matter hyperintensity grade and cerebral atrophy grade.Methods The data of 213 patients with CSVD were analyzed retro-spectively.The semi-quantitative Fazekas visual score of brain MR was used to evaluate the white matter hyperintensity,and cerebral atrophy was evaluated by the whole cerebral cortex atrophy grade.Mini-mental state examination(MMSE)and Montreal cognitive assessment(Mo CA)were used to evaluate each patient and to classify according to the results.Results There was a statistically sig-nificant difference in age between male and female patients with CSVD(P=0.04,t=4.288).The mean age of males[(66.5±10.3)years]was less than females[(69.5±10.0)years].There was significant difference between patients with different gender and history of hypertension(P=0.02,t=5.424).There were statistical differences between white matter hyperintensity Fazekes grade and MMSE and Mo CA scores(P<0.001,χ2=5.639;P<0.001,χ2=5.843),and there were statistical differences between whole cerebral cortex atrophy grade and MMSE score(P=0.036,χ2=2.895).Conclusion There is a certain correlation between cognitive impairment of CSVD and head MR imaging evaluation grade.