ObjectiveTo explore the effects of Jingui Shenqiwan （JSW） and Liuwei Dihuangwan （LDW） on the reproductive ability and brain function of normal mice and compare the actions of the two medications. MethodsSeven groups of female and male mice were divided at a ratio of 2∶1. Except for the control group， the other six groups were as follows： a group of both males and females receiving JSW （3.0 g·kg^-1）， a group of both males and females receiving LDW （4.5 g·kg^-1）， a group of males receiving water and females receiving JSW， a group of males receiving water while females receiving LDW， a group of females receiving water while males receiving JSW， and a group of females receiving water while males receiving LDW. Each group was administered the drug for 14 days and then caged together at a 2∶1 （female∶male） ratio to detect the number of pregnant mice and calculate the pregnancy rate. Pregnant mice continued receiving the drug until they naturally gave birth， which was followed by the observation of newborn mice， calculation of their average number， and the measurement of the offspring's preference for sugar water and neonatal recognition index. At the end of the experiment， the weights of the thymus and spleen were measured to calculate the organ coefficients， and mRNA or protein expression was analyzed in the brain and testes or ovaries. A 1% sucrose solution was used to examine the euphoria of their brain reward systems， while novel object recognition test （NOR） was applied to assess their memory capabilities. mRNA expression was detected using real-time quantitative polymerase chain reaction （Real-time PCR） assay， and protein expression was analyzed with Western blot. ResultsCompared with the control group， oral administration of JSW to both male and female mice for 14 days significantly increased the pregnancy rate of female mice on day 2 after being caged together （P<0.05）， while LDW showed a trend but no statistical significance. Additionally， compared with the control group， JSW could upregulate the gene expression of gonadotropin-releasing hormone （GnRH） in the thalamus， as well as reproductive stem cell factor （SCF） and tyrosine kinase receptor （c-Kit） in the testes and reproductive stem cell marker mouse vasa homologue （MVH） in the ovaries， upregulate the expression of proteins influencing neuronal functional activity， such as brain-derived neurotrophic factor （BDNF）， in hippocampal neurons （P<0.05）， and enhance sucrose preference in male mice （P<0.05）. Compared with the control group， JSW significantly increased sucrose preference and novel object recognition index in offspring mice （P<0.05）， which was related to the upregulation of hippocampal dopamine D1 receptor （D1R） and N-methyl-D-aspartate receptor （Nmdar） gene expression. Compared with the control group， both JSW and LDW could upregulate the protein expression of glucocorticoid receptor （GR）， BDNF， and tyrosine kinase receptor B （TrkB） in the hippocampus of offspring mice （P<0.05）. ConclusionJSW significantly enhances the reproductive ability of normal mice， which is not only related to the release of gonadotropin but also associated with its regulation of brain function. Additionally， JSW has a certain regulatory effect on the brain function of the offspring mice.

OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: To compare the effects of different chest compression rates (60-140 times/min) on hemodynamic parameters, return of spontaneous circulation (ROSC), resuscitation success, and survival in a porcine model of cardiac arrest (CA) followed by cardiopulmonary resuscitation (CPR). METHODS: Forty healthy male domestic pigs were randomly divided into five groups based on chest compression rate: 60, 80, 100, 120, and 140 times/min (n = 8). All animals underwent standard anesthesia and tracheal intubation. A catheter was inserted via the left femoral artery into the thoracic aorta to monitor aortic pressure (AOP), and another via the right external jugular vein into the right atrium to monitor right atrial pressure (RAP). In each group, animals were implanted with a stimulating electrode via the right external jugular vein to the endocardium, and ventricular fibrillation (VF) was induced by delivering alternating current stimulation, resulting in CA. After a 1-minute, manual chest compressions were performed at the assigned rate with a compression depth of 5 cm. The first defibrillation was delivered after 2 minutes of CPR. No epinephrine or other pharmacologic agents were administered during the entire resuscitation process. From 1 minute before VF induction to 10 minutes after ROSC, dynamic monitoring of AOP, coronary perfusion pressure (CPP), and partial pressure of end-tidal carbon dioxide (P_ETCO₂). Cortical ultrastructure was examined 24 hours post-ROSC using transmission electron microscopy. RESULTS: With increasing compression rates, both the total number of defibrillations and cumulative defibrillation energy significantly decreased, reaching their lowest levels in the 120 times/min group. The number of defibrillations decreased from (4.88±0.83) times in the 60 times/min group to (2.25±0.71) times in the 120 compressions/min group, and energy from (975.00±166.90)J to (450.00±141.42)J. However, both parameters increased again in the 140 times/min group [(4.75±1.04)times, (950.00±207.02)J], the differences among the groups were statistically significant (both P < 0.01). As compression frequency increased, P_ETCO₂, pre-defibrillation AOP and CPP significantly improved, peaking in the 120 times/min group [compared with the 60 times/min group, P_ETCO₂ (mmHg, 1 mmHg≈0.133 kPa): 18.69±1.98 vs. 8.67±1.30, AOP (mmHg): 95.13±7.06 vs. 71.00±6.41, CPP (mmHg): 14.88±6.92 vs. 8.57±3.42]. However, in the 140 times/min group, these values declined significantly again [P_ETCO₂, AOP, and CPP were (10.59±1.40), (72.38±11.49), and (10.36±4.57) mmHg, respectively], the differences among the groups were statistically significant (all P < 0.01). The number of animals achieving ROSC, successful resuscitation, and 24-hour survival increased with higher compression rates, reaching a peak in the 120 times/min group (compared with the 60 times/min group, ROSC: 7 vs. 2, successful resuscitation: 7 vs. 2, 24-hour survival: 7 vs.1), then decreased again in the 140 times/min group (the animals that ROSC, successfully recovered and survived for 24 hours were 3, 3, and 2, respectively). Transmission electron microscopy revealed that in the 60, 80, and 140 times/min groups, nuclear membranes in cerebral tissue were irregular and incomplete, nucleoli were indistinct, and mitochondria were swollen with reduced cristae and abnormal morphology. In contrast, the 100 times/min and 120 times/min groups exhibited significantly attenuated ultrastructural damage. CONCLUSIONS Among the tested chest compression rates of 60-140 times/min, a chest compressions frequency of 120 times/min is the most favorable hemodynamic profile and outcomes during CPR in a porcine CA model. However, due to the wide spacing between groups, further investigation is needed to determine the optimal compression rate range more precisely.
Animals ; Cardiopulmonary Resuscitation/methods* ; Swine ; Male ; Heart Arrest/therapy* ; Heart Massage/methods* ; Hemodynamics

Objective To explore the relationship between serum chitosinase 3-like protein 1(CHI3L1)and Syndecan-1(SDC1)levels and bone metabolism in elderly patients with type 2 diabetes mellitus and their predictive efficacy on osteoporosis.Methods A total of 412 elderly patients with type 2 diabetes admitted to this hospital from May 2019 to May 2023 were included in this study,and were divided into normal bone mass group(n=151),reduced bone mass group(n=138)and osteoporosis group(n=123)according to the iffer-ences in bone mineral density.Serum CHI3L1 and SDC1 levels were detected by enzyme-linked immunosor-bent assay,and serum levels of type 1 collagen cross-linked carboxyl terminal peptide(CTX),25-hydroxyvita-min D[25-(OH)D],osteocalcin(OC),and type 1 procollagen N-terminal propeptide(P1NP)were deter-mined by automatic chemiluminescence immunoassay.Pearson correlation analysis was used to investigate the relationship between serum CHI3L1,SDC1 and bone metabolism in elderly patients with type 2 diabetes.Re-ceiver operating characteristic(ROC)curve was drawn to evaluate the predictive value of serum CHI3L1 and SDC1 on osteoporosis in elderly patients with type 2 diabetes.Multivariate Logistic regression analysis was used to investigate the influencing factors of osteoporosis in elderly patients with type 2 diabetes.Results There were significant differences in diabetes course,fasting blood glucose,HbA1c and HDL-C a-mong normal bone mass group,decreased bone mass group and osteoporosis group(P＜0.05).The levels of serum CHI3L1,25-(OH)D,P1NP and osteocalcin in osteoporosis group were lower than those in osteopenia group,and those in osteopenia group were lower than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum SDC1 and CTX levels in osteoporosis group were higher than those in osteopenia group,and those in osteopenia group were higher than those in normal bone mass group,the differences were statistically significant(P＜0.05).Serum CHI3L1 was positively correlated with 25-(OH)D,P1NP and OC(P＜0.05),and negatively correlated with CTX(P＜0.05).Serum SDC1 was negatively correlated with 25-(OH)D,P1NP,OC(P＜0.05),and positively correlated with CTX(P＜0.05).The area under the curve(AUC)of serum CHI3L1,SDC1 and their combination predicted osteoporosis in elderly pa-tients with type 2 diabetes were 0.851,0.772 and 0.904,respectively.Multivariate Logistic regression analysis showed that long duration of diabetes,increased HbA1c,high expression of OC,CHI3L1＞4.16 ng/mL,SDC1≥50.94 ng/mL were all influential factors for osteoporosis in elderly patients with type 2 diabetes(P＜0.05).Conclusion Low expression of CHI3L1 and high expression of SDC1 in serum are associated with ab-normal bone metabolism in elderly patients with type 2 diabetes.These two indexes are expected to be used as biological markers to predict osteoporosis in elderly patients with type 2 diabetes.

Objective:To develop a camelid single-domain antibody (SdAb) recognizing linear B-cell epitopes in glutamate dehydrogenase of Clostridium difficile(CD-GDH), and to apply it in Western blot and ELISA. Methods:Purified recombinant CD-GDH was used as bait to screen phage-displayed camelid SdAb library and obtain positive clones. Then those clones were confirmed by Western blot, and their variable domain of heavy chain of heavy chain antibody(VHH) nucleotide sequence were determined. The VHH sequence was synthesized after codon optimization and cloned into the expression vector pET28a. The SdAb was then expressed and purified, and its ability to detect CD-GDH protein in multiple assays was further explored.Results:Six positive clones were obtained, among which clone GA4 was chosen for recombinant expression in Escherichia coli and further purification. The purified GA4 binded well with CD-GDH with a Kd value of 3 nmol/L. In Western blot and ELISA, GA4 was proven to be able to selectively detect both recombinant and endogenous CD-GDH. Conclusions:A camelid SdAb targeting a linear B-cell epitope in CD-GDH is successfully developed, which provides a very useful tool for detecting CD-GDH.

ObjectiveTo explore the effect of Shenge Bushen Capsules （SBC） on sexual development in normal 3-week-old mice. MethodsThe experiment consisted of two parts. In the first part， mice were divided into four groups： The control group and the low， medium， and high-dose SBC groups （234.7， 469.4， 938.7 mg·kg^-1， respectively）. In the second part， mice were divided into four groups： Control group， Pseudostellariae Radix polysaccharide （PRP） group， total flavonoids group， and SBC group， all receiving a dose of 469.4 mg·kg^-1. After 7 days of administration， the vaginal opening of female mice and the descent of testes and scrotum in male mice， as well as the ovarian and testicular organ indices， were observed. After 4 weeks of administration， female and male mice were housed together for 2 days， and the pregnancy rate of females was monitored. After delivery， the pregnant female mice continued receiving the treatment for 4 weeks， and the sexual development of their offspring， including vaginal opening， testicular descent， and organ indices of ovaries and testes， was observed. Serum sex hormones were measured by enzyme-linked immunosorbent assay （ELISA）， and the expression of gonadotropin-releasing hormone （GnRH） and growth hormone （GH） proteins in the hypothalamus was assessed by Western blot. ResultsCompared with the control group， there was no significant effect on the vaginal opening of female mice or the descent of testes in male mice after 7 days of SBC administration. After 4 weeks of administration， the pregnancy rate in the low-dose group was significantly reduced （P<0.05）， but no significant effects were observed in the other groups. The three doses of SBC did not significantly affect the ovarian or testicular organ indices， and there was no significant upregulation in the expression of GnRH or GH in the hypothalamus. The primary component of SBC， Pseudostellariae Radix polysaccharide， significantly reduced the vaginal opening in female mice after 7 days of administration （P<0.05）. After 4 weeks， the serum estradiol levels of non-pregnant female mice were decreased （P<0.05）， but there was no significant effect on the expression of GnRH or GH proteins in the hypothalamus of either male or female mice. Additionally， there were no significant effects on precocious puberty indicators， such as vaginal opening and testicular descent， in the offspring mice. ConclusionSBC does not significantly promote precocious puberty in young mice， and it does not have any noticeable effects on the pregnancy rate of adult mice or the sexual development of their offspring.

Objective　To analyze the clinical characteristics and prognostic factors for clinical cure in chronic hepatitis B virus (HBV) infected patients with pegylated interferon-α-2b (PEG-IFN-α-2b) based therapy. Methods　This is a retrospective study. Chronic HBV infected patients receiving PEG-IFN-α-2b therapy were enrolled in Yuncheng Central Hospital affiliated to Shanxi Medical University between August 2020 and November 2023. Treatment-naïve patients received PEG-IFN-α-2b monotherapy, while nucleoside (acid) analogs (NAs)-experienced patients received PEG-IFN-α-2b add-on therapy. The study endpoint was hepatitis B surface antigen (HBsAg) negative in accompany with HBV DNA below the detection limit (course of treatment < 48 weeks) or treatment for 48 weeks. The general characteristics, virological variables, blood routine test, and liver function of patients were collected at baseline and study endpoint. Student’s t test or Mann-Whitney U test was used for comparison. The prognostic factors of clinical cure were examined using univariate and multivariate stepwise logistic regression models. Results　A total of 61 chronic HBV infected patients were enrolled, including 39 males and 22 females. The age were (39.13±7.53) years. Twenty-one cases were treatment-naïve, while 40 patients were NAs-experienced. Nineteen cases were positive for HBV DNA at baseline. The baseline HBsAg levels were 211.30(50.93, 2 110.00) IU/mL. Thirty-four patients achieved clinical cure at the study endpoint with 25.50 weeks of median course of PEG-IFN-α-2b treatment. Twenty-seven patients did not achieve clinical cure at the study endpoint, and the course of treatment was 48 weeks. Clinical cure group had significant lower baseline HBsAg level when compared with non-clinical cure group [78.66(19.54, 204.60) IU/mL vs 2 078.00(442.20, 4 237.00) IU/mL, P<0.001]. At the study endpoint, the white blood cell, platelet, red blood cell, hemoglobin levels were lower than those in baseline (P<0.05), while alanine aminotransferase and asparatate aminotransferase levels were higher than those in baseline (P<0.05). There were no remarkable differences in blood routine tests or liver function between clinical cure and non-clinical cure group at either baseline or study endpoint (P>0.05). Baseline low HBsAg level was a predictor for clinical cure in patients receiving PEG-IFN-α-2b therapy (OR=0.998, 95%CI: 0.998-0.999). No severe adverse events were happened during therapy. Conclusion　PEG-IFN-α-2b-based therapy was well-tolerant, and could achieve high rate of clinical cure in chronic HBV-infected patients who had low baseline HBsAg level.

AIM:To investigate the expression of AU-rich element RNA-binding factor 1(AUF1),an RNA-binding protein,in hepatocellular carcinoma(HCC),and to explore its potential role in HCC progression through regula-tion of metabolism-related genes.METHODS:A tissue microarray containing 99 HCC samples and 95 adjacent nontu-morous liver tissues was used to assess AUF1 expression.The associations between AUF1 expression and HCC clinical pa-rameters were analysed using the GEPIA and UALCAN databases.The AUF1 gene was knocked down in human hepato-blastoma HepG2 cells by siRNA,and transcriptomic and TMT quantitative proteomic analyses were performed to identify alterations in metabolism-related genes.RESULTS:The AUF1 expression was significantly elevated in HCC tissues and correlated with a poor prognosis.Knockdown of AUF1 in HepG2 cells resulted in reduced cell viability and increased apop-tosis.Integrative analyses of transcriptomic and proteomic data revealed that AUF1 knockdown in HepG2 cells led to up-regulation of carboxylesterase 3(CES3),fibrinogen gamma chain(FGG)and 4-hydroxy-2-oxoglutarate aldolase 1(HOGA1),and down-regulation of lamin B receptor(LBR),riboflavin kinase(RFK),sterol O-acyltransferase 1(SOAT1)and TWIST neighbor(TWISTNB).Clinical data from GEPIA and UALCAN databases suggested that the expression of these metabolism-related genes in HCC patients exhibited an opposite trend.CONCLUSION:Our findings suggest that AUF1 is highly expressed in HCC,and may contribute to tumor progression and poor prognosis by modulating the expres-sion of a series of metabolism-related genes.