OBJECTIVE: To explore the expression regulation of lipid metabolism gene ABHD5 in testes. METHODS: Differential gene analysis was performed by integrating databases of TCGA and GTEx to identify the target gene ABHD5. The expression trends of ABHD5 gene in testicular carcinoma tissue were analyzed. Human testis single-cell atlases were obtained from the Human Protein Atlas and Male Health Atlas databases to determine the expression distribution of ABHD5 across different testicular cell types. Additionally, the GTEx database was utilized to visualize the expression pattern of ABHD5 in the testis, thereby enhancing the understanding of its transcriptional profile. The relationship between ABHD5 expression and age was assessed through integrated database analysis. Western blotting and immunofluorescence were performed to detect differential expressions of ABHD5 in testicular tissues of young and aged mice respectively. RESULTS: The TCGA database indicated that the expression of ABHD5 in human testicular carcinoma tissue was significantly lower than that in normal testicular tissue which showed a negative correlation with patient survival. ABHD5 was highly expressed in germ cells of the testis reveaked from Human Protein Atlas and Male Health Atlas databases. The stability of ABHD5 protein was crucial for testicular tissue, and its expression decreased with age. Furthermore, Western blot and immunofluorescence staining demonstrated that ABHD5 expression in the testicular tissue of aged mice was significantly lower than that in young mice. CONCLUSION ABHD5 plays an important role in testicular tissue, and may be inseparable from testicular tumors and reproductive aging. However, its mechanism of action remains to be further studied.
Male ; Animals ; Mice ; Testis/metabolism* ; Humans ; Lipid Metabolism/genetics* ; 1-Acylglycerol-3-Phosphate O-Acyltransferase/metabolism* ; Testicular Neoplasms/metabolism*

Objective To compare the effectiveness of TiRobot assisted F screw technique and inverted triangle parallel nail internal fixation in the treatment of unstable femoral neck fractures.Methods A retrospective analysis was conducted on 72 patients with unstable femoral neck fractures who were treated with percutaneous cannulated screw fixation assisted with TiRobot Orthopaedic robot from December 2019 to April 2021.Among them,37 patients were treated with F screw internal fixa-tion,including 16 males and 21 females,aged47 to 64years old with an average of(53.87±5.28)years old;According to Pauwels classification,there were 1 case of type Ⅰ,19 cases of type Ⅱ,17 cases of type Ⅲ;8 cases of combined medical diseases;17 cases of falling,8 cases of traffic accident and 12 cases of falling from height;The time from injury to operation was 29 to 49 hours with average of(35.00±7.34)hours.Another 35 cases used internal fixation with an inverted triangle parallel nail,including 13 males and 22 females with an average age of 46 to 63 years old(52.36±5.05)years old;According to the Pauwels injury classifi-cation:there were 2 cases of type Ⅰ,21 cases of type Ⅱ,12 cases of type Ⅲ;6 cases of medical diseases,15 cases of falling in-jury,9 cases of traffic accident,11 cases of falling injury;The time from injury to operation was 30 to 45 hours with an average of(33.00±6.83)h.The intraoperative blood loss,operation time,intraoperative fluoroscopy times,follow-up time,fracture healing time,postoperative complications were observed and compared between the two groups.The hip joint function was e-valuated by Harris score at 6 months and 12 months after operation.Results There was no significant difference in operation time,intraoperative blood loss,intraoperative fluoroscopy times and other intraoperative data between two groups(P＞0.05).Both groups were followed up regularly,and the follow-up time was 12 to 16 months.The fracture healing time and Harris score of the F screw internal fixation group were better than those of the inverted triangle parallel nail internal fixation group(P＜0.05).There was 1 case of femoral neck shortening in the F screw internal fixation group,1 case of nonunion,1 case of nail withdrawal,and 1 case of lower extremity deep vein thrombosis in the inverted triangle internal fixation group.The incidence of complications in the F screw internal fixation group was lower than that in the inverted triangle parallel nail internal fixation group(P＜0.05).Conclusion Percutaneous cannulated F screw technique using Tirobot navigation positioning system is a safe and effective treatment for patients with unstable femoral neck fractures.It can significantly shorten the fracture healing time,reduce the incidence of postoperative complications,significantly improve hip joint function,and improve the quality of life.

"Solid-liquid excipients" co-production is one of the typical processing methods of excipients used from ancient times to the present day, and is widely applied in various processing schools and regional specialty varieties. This method significantly reduces the toxicity of traditional Chinese medicine(TCM), moderates medicinal properties, and enhances clinical efficacy. However, modern scientific research has given it limited attention, and many co-production methods of "solid-liquid excipients" have not been applied in production and practice. This paper reviewed the historical development of "solid-liquid excipients" co-production, outlined modern processing standards and methods in different processing schools, and further elaborated on the purposes and effects of this co-production method. This study is expected to provide references and evidence for further in-depth research, inheritance, innovation, and practical application.
Chemistry, Pharmaceutical/history* ; Drug Compounding/methods* ; Drugs, Chinese Herbal/chemistry* ; Excipients/chemistry* ; History, 20th Century ; History, 21st Century ; History, Ancient ; Medicine, Chinese Traditional/history*

This study aims to investigate the protective effect and potential mechanism of Jingfang Granules(JF) on the mouse model of chronic fatigue syndrome(CFS). Mice were randomized into normal, model, and low-, medium-, and high-dose(0.9, 1.8, and 3.6 g·kg~(-1)·d~(-1), respectively) JF groups according to the body weight. In addition to the normal group, other groups of mice received exhaustive swimming training and tail suspension training every day for the modeling of CFS. The mice in each administration group were administrated with JF at the corresponding dose by gavage, and those in the other groups were administrated with an equal amount of purified water. The exhaustive swimming and tail suspension tests were conducted in each group. The UV-glutamate dehydrogenase method was used to determine the serum level of urea nitrogen(UREA), and the lactate dehydrogenase(LDH) assay kit was used to determine the LDH level. Enzyme-linked immunosorbent assay was employed to measure the levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) in the serum, muscle tissue, and brain tissue of mice in each group. Western blot was employed to determine the expression levels of Toll-like receptor 4(TLR4), myeloid differentiation factor 88(MyD88), nuclear factor-kappa B(NF-κB) and their phosphorylated proteins in the muscle tissue of mice. The 16S rDNA sequencing and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) were adopted to detect the changes of intestinal flora and intestinal metabolites in mice. Compared with the model group, JF significantly prolonged the swimming exhaustion time and shortened the tail suspension time of the model mice, lowered the levels of LDH and UREA in the serum as well as the levels of IL-6 and TNF-α in the serum, muscle tissue, and brain tissue of CFS mice. In addition, JF down-regulated the expression of TLR4, MyD88, and p-NF-κB/NF-κB in the muscle tissue of CFS mice compared with the model group. The results of 16S rDNA sequencing demonstrated that JF ameliorated the intestinal flora disorder of CFS mice. The results of UPLC-MS/MS revealed that JF significantly affected the histidine metabolism pathway in the intestinal tract of CFS mice. Spearman analysis displayed that histamine, a metabolite involved in histidine metabolism, was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. The metabolite imidazole-4-acetaldehyde was negatively correlated with the abundance of Clostridia＿UCG-014, Dubosiella, and RF39 and positively correlated with the abundance of Coriobacteriaceae＿UCG-002. In conclusion, JF can increase the swimming exhaustion time, reduce the immobility time of tail suspension, lower serum LDH and UREA levels, and alleviate inflammation response. It may exert the therapeutic effect by improving intestinal flora homeostasis and inhibiting histidine metabolism by down-regulating the expression of proteins in the TLR4/MyD88/NF-κB signaling pathway, thereby relieving the symptoms of CFS in mice.
Animals ; Mice ; Gastrointestinal Microbiome/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Metabolomics ; Fatigue Syndrome, Chronic/genetics* ; NF-kappa B/genetics* ; Humans ; Interleukin-6/genetics* ; Myeloid Differentiation Factor 88/genetics* ; Toll-Like Receptor 4/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Disease Models, Animal

The cerebellum is heavily connected with other brain regions, sub-serving not only motor but also nonmotor functions. Genetic mutations leading to cerebellar dysfunction are associated with mental diseases, but cerebellar outputs have not been systematically studied in this context. Here, we present three dimensional distributions of 50,168 target neurons of cerebellar nuclei (CN) from wild-type mice and Nlgn3R451C mutant mice, a mouse model for autism. Our results derived from 36 target nuclei show that the projections from CN to thalamus, midbrain and brainstem are differentially affected by Nlgn3R451C mutation. Importantly, Nlgn3R451C mutation altered the innervation power of CN→zona incerta (ZI) pathway, and chemogenetic inhibition of a neuronal subpopulation in the ZI that receives inputs from the CN rescues social defects in Nlgn3R451C mice. Our study highlights potential role of cerebellar outputs in the pathogenesis of autism and provides potential new therapeutic strategy for this disease.
Animals ; Mice ; Disease Models, Animal ; Cerebellar Nuclei ; Autistic Disorder/pathology* ; Neurons/metabolism* ; Mutation ; Nerve Tissue Proteins/metabolism* ; Male ; Membrane Proteins ; Cell Adhesion Molecules, Neuronal

Hepatotoxicity induced by bioactive constituents in traditional Chinese medicines or herbs,such as bavachin(BV)in Fructus Psoraleae,has a prolonged latency to overt drug-induced liver injury in the clinic.Several studies have described BV-induced liver damage and underlying toxicity mechanisms,but little attention has been paid to the deciphering of organisms or cellular responses to BV at no-observed-adverse-effect level,and the underlying molecular mechanisms and specific indicators are also lacking during the asymptomatic phase,making it much harder for early recognition of hepatotoxicity.Here,we treated mice with BV for 7 days and did not detect any abnormalities in biochemical tests,but found subtle steatosis in BV-treated hepatocytes.We then profiled the gene expression of hepatocytes and non-parenchymal cells at single-cell resolution and discovered three types of hepatocyte subsets in the BV-treated liver.Among these,the hepa3 subtype suffered from a vast alteration in lipid metabolism,which was characterized by enhanced expression of apolipoproteins,carboxylesterases,and stearoyl-CoA desaturase 1(Scd1).In particular,increased Scd1 promoted monounsaturated fatty acids(MUFAs)syn-thesis and was considered to be related to BV-induced steatosis and polyunsaturated fatty acids(PUFAs)generation,which participates in the initiation of ferroptosis.Additionally,we demonstrated that mul-tiple intrinsic transcription factors,including Srebf1 and Hnf4a,and extrinsic signals from niche cells may regulate the above-mentioned molecular events in BV-treated hepatocytes.Collectively,our study deciphered the features of hepatocytes in response to BV insult,decoded the underlying molecular mechanisms,and suggested that Scd1 could be a hub molecule for the prediction of hepatotoxicity at an early stage.

Pheretima,also called"earthworms",is a well-known animal-derived traditional Chinese medicine that is extensively used in over 50 Chinese patent medicines(CPMs)in Chinese Pharmacopoeia(2020 edi-tion).However,its zoological origin is unclear,both in the herbal market and CPMs.In this study,a strategy for integrating in-house annotated protein databases constructed from close evolutionary relationship-sourced RNA sequencing data from public archival resources and various sequencing al-gorithms(restricted search,open search,and de novo)was developed to characterize the phenotype of natural peptides of three major commercial species of Pheretima,including Pheretima aspergillum(PA),Pheretima vulgaris(PV),and Metaphire magna(MM).We identified 10,477 natural peptides in the PA,7,451 in PV,and 5,896 in MM samples.Five specific signature peptides were screened and then validated using synthetic peptides;these demonstrated robust specificity for the authentication of PA,PV,and MM.Finally,all marker peptides were successfully applied to identify the zoological origins of Brain Heart capsules and Xiaohuoluo pills,revealing the inconsistent Pheretima species used in these CPMs.In conclusion,our integrated strategy could be used for the in-depth characterization of natural peptides of other animal-derived traditional Chinese medicines,especially non-model species with poorly annotated protein databases.

Objective: To explore the current situation of fetal heart defects in Yunnan Province and surrounding high altitude areas and the social factors affecting pregnancy outcome. Methods: This is a retrospective study. Pregnant woman who underwent fetal echocardiography and diagnosed as fetal cardiac defects in Yunnan Fuwai Cardiovascular Hospital from June 2017 to January 2021 were included. According to the clinical prognostic risk scoring system and grading criteria of fetal cardiac birth defects, the cases were divided into grade Ⅰ to Ⅳ. The disease distribution and proportion of each prognostic grade, pregnancy outcomes were analyzed and compared. The cases were divided into continued pregnancy group and terminated pregnancy group according to pregnancy outcome. The social factors that may affect the selection of pregnancy outcomes were analyzed by multivariate logistic regression analysis. Results: A total of 4 929 fetal echocardiography examination data were collected, and 4 464 cases (90.57%) were from Yunnan Province and surrounding high altitude areas. 2 166 cases of heart defects were finally analyzed, including 998 cases of congenital heart disease (CHD), 93 cases of cardiac tumors, cardiomyopathy and arrhythmia, 1 075 cases of foramen ovale, ductus arteriosus abnormalities and normal variations. The pregnant women were (29.2±5.0) years old with (25.6±3.8) gestational weeks. The number of cases with prognostic grade from Ⅰ to Ⅳ was 1 037 (47.88%), 620 (28.62%), 314 (14.50%), and 44 (2.03%), respectively. And 151 cases (6.97%) were not classified. The cases of normal variation and thin aortic arch development accounted for 42.66% (924/2 166), 5.22% (113/2 166), respectively. The top 3 diseases of grade Ⅱ were ventricular septal defect, coarctation of aorta and mild-moderate pulmonary stenosis, respectively, and their distribution was 11.63% (252/2 166), 3.92% (85/2 166) and 2.35% (51/2 166) respectively in all cases of heart defects, and 25.25% (252/998), 8.52% (85/998) and 5.11% (51/998) respectively in cases of CHD. Among the cases rated as grade Ⅲ and Ⅳ, most of them were complicated congenital heart disease, and the disease types are scattered. The more common cases in grade Ⅲ were complete transposition of great arteries (accounting for 2.40% (52/2 166) of all cases with heart defects, 5.21% (52/998) of all cases with CHD) and pulmonary artery occlusion (type Ⅰ to Ⅲ) with ventricular septal defect (accounting for 2.17% (47/2 166) of all cases with heart defects, and 4.71% (47/998) of all cases with CHD). In grade Ⅳ, single ventricle (0.74% (16/2 166) of all cases with heart defects, 1.60% (16/998) of all cases with CHD) and left ventricular dysplasia syndrome (0.65% (14/2 166) of all cases with heart defects, 1.40% (14/998) of all cases with CHD) are more common. A total of 1 084 cases were successfully followed up, and 675 cases were born, 392 cases were terminated, spontaneous abortion occurred in 17 cases. The proportion of terminated pregnancy cases was significantly increased from grade Ⅰ to Ⅳ, accounting for 5.24% (21/401), 27.78% (70/252), 89.54% (214/239) and 95.56% (43/45), respectively. Among the terminated pregnancy cases, those with grade Ⅲ accounted for the highest proportion (54.59% (214/392)). The distribution of terminated pregnancy cases was mainly complex congenital malformations or diseases with very poor prognosis (pregnancy outcome grade Ⅲ and Ⅳ), and proportion of terminated pregnancy with pregnancy outcome grade Ⅰ and Ⅱ cases (normal variation or good prognosis) accounted for 5.36% (21/392) and 17.86% (70/392), respectively. The results of multivariate logistic regression analysis showed that pregnant women with low education (high school and below: OR=2.73, 95%CI 1.26-5.93, P<0.001; illiteracy: OR=3.27, 95%CI 1.29-7.10, P<0.001) and low family income (Annual income<100 000 yuan: OR=2.47, 95%CI 1.69-5.12, P<0.001) were more likely to choose termination of pregnancy in case of fetal heart defect. Conclusion: In Yunnan province and the surrounding high altitude areas, the disease distribution of fetal heart defect is mainly simple or low-risk disease, but the complex malformation, especially the disease with poor pregnancy outcome, accounts for a relative high proportion. Pregnancy termination also occurs in some cases with good pregnancy outcome. The education level and family income of pregnant women may affect their choice of pregnancy outcome in case of fetal heart defect.
Pregnancy ; Female ; Humans ; Young Adult ; Adult ; Retrospective Studies ; Altitude ; China/epidemiology* ; Heart Defects, Congenital/diagnostic imaging* ; Heart Septal Defects, Ventricular ; Echocardiography ; Fetal Heart/diagnostic imaging*

Background: The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values. Methods: In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. Results: The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P<0.05). TSH, total thyroxine (TT4), and ATPO levels were significantly correlated with age (P<0.05). The serum levels of TSH, ATG, and ATPO in men were significantly lower than in women; in contrast, the serum TT3 level was significantly higher in men than in women (P<0.05). Serum TSH, TT3, TT4, and ATG levels differed across age groups (P<0.05), but no such variation was observed for ATG levels (P>0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values. Conclusion The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer’s manual. Validated sex-specific values are required for diagnosing thyroid diseases.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve