Objective: To investigate the association between brain and muscle Arnt like protein 1( BMAL 1) gene and ambulatory blood pressure (ABP) parameters in college students, and to explore the influence of the interaction between the gene and weight status on the ABP levels, so as to provide reference for early prevention of chronic cardiovascular diseases related to hypertension. Methods: During September 2022 to June 2024, a total of 510 college students were recruited from a university in Changsha, China for on site questionnaire investigation, physical examination, ABP monitoring and genotyping testing. Multiple linear regression method was used to explore the association between the BMAL 1 gene and ABP indicators. An interaction term was included in the general linear model of multiple linear regression to analyze the interactive effects of BMAL 1 gene polymorphisms and weight status on ABP levels. Results: The prevalence of abnormal 24 hour blood pressure, abnormal daytime blood pressure, and abnormal nighttime blood pressure were 3.3%, 3.1%, and 3.9%, respectively. Multiple linear regression analysis showed that the BMAL 1/rs7950226 polymorphism was positively correlated with the 24 hour diastolic blood pressure(DBP) and the daytime DBP level after adjusting for gender, age, and body mass index( β =0.87,0.99, both P <0.05). Also, interaction between BMAL 1/ rs 11022775 and weight status on the nighttime DBP level ( P interaction =0.03) was found. The CC genotype carriers had significantly higher nighttime DBP level ( β =3.52, P <0.05) among overweight/obesity college students, but no differences in nocturnal DBP levels were observed between CC genotype carriers and TT+CT genotype carriers among college students with normal body weight( P > 0.05). Conclusions The rs 7950226 polymorphism is associated with 24 hours DBP and daytime DBP levels. Significant interaction between rs 11022775 with weight status on the nighttime DBP level is found among college students.

This study aimed to evaluate the efficacy and safety of combining albumin-bound paclitaxel (abpaclitaxel) and anlotinib for ovarian cancer. In this study, 44 patients diagnosed with platinum-resistant ovarian cancer were enrolled. Patients received ab-paclitaxel along with anlotinib until disease progression or intolerable toxicity. Efficacy was assessed according to RECIST 1.1 criteria or Rustin's criteria. The primary endpoint was the investigator-evaluated objective response rate (ORR). 44 patients were enrolled between January 2021 and March 2023 with a median age of 49 years. Twenty-nine had measurable lesions and 15 had non-measurable lesions. Overall, the investigator-evaluated ORR was 56.8% (25/44; 95% CI 0.411-0.713) in intention-to-treat population and 58.1% (25/43; 95% CI 0.422-0.726) in per-protocol population. The median progression-free survival was 9.8 months, and the median duration of response was 7.4 months. For safety, grade 3/4 adverse events (AEs) included leukopenia, gum pain, hypertension, and hand-foot syndrome. The response rates were 55.0% (11/20) in patients with previous use of antiangiogenic reagents and who had previous use of PARP inhibitors. The combination of ab-paclitaxel and anlotinib showed promising anti-tumor activity and a manageable safety profile in platinum-resistant ovarian cancer. Patients with previous use of antiangiogenic drugs or PARP inhibitors still benefited from this protocol.
Humans ; Female ; Middle Aged ; Indoles/therapeutic use* ; Quinolines/therapeutic use* ; Carcinoma, Ovarian Epithelial/drug therapy* ; Adult ; Ovarian Neoplasms/drug therapy* ; Prospective Studies ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Aged ; Drug Resistance, Neoplasm ; Albumin-Bound Paclitaxel/therapeutic use* ; Neoplasm Recurrence, Local/drug therapy* ; Progression-Free Survival ; Paclitaxel/administration & dosage* ; Treatment Outcome

BACKGROUND:Treadmill training is one of the effective ways to promote the recovery of motor function after spinal cord injury.Treadmill training can promote neurogenesis,but the effect of different intensities of treadmill training on the activation of endogenous stem cells is still unclear. OBJECTIVE:To analyze the activation effect of different intensities of treadmill training on endogenous neural stem cells in the spinal cord of mice after spinal cord injury. METHODS:Fifty female C57BL/6J mice were divided into control group,spinal cord injury group,low-,moderate-,and high-intensity exercise groups with 10 mice in each group by random number table method.T10 segment spinal cord injury model was constructed by the clamp method in spinal cord injury group,low-,moderate-,and high-intensity exercise groups.On day 7 after spinal cord injury,mice in the low-,moderate-,and high-intensity exercise groups were respectively trained on the treadmill with corresponding intensity,3 times/d,10 min/times,6 times a week for 28 consecutive days.At 3,7,14,21,and 28 days after treadmill training,the hind limb motor function was evaluated by BMS score.At 28 days after treadmill training,the spinal cord tissue of the injured area was obtained,and the expression of epidermal growth factor receptor,glial fibrillary acidic protein,and 5-Ethynyl-2'-deoxyuridine(EdU),a proliferative marker,was detected.Hematoxylin-eosin staining was used to observe the morphology of spinal cord. RESULTS AND CONCLUSION:(1)The BMS score of mice in the spinal cord injury group was lower than that in the control group(P<0.05).With the extension of treadmill training time,the BMS scores of mice with spinal cord injury gradually increased,and the BMS scores of mice in moderate-intensity exercise group on days 14 and 21 after treadmill training were higher than those in spinal cord injury group and low-and high-intensity exercise groups(P<0.05).The BMS score of mice in moderate-and high-intensity exercise group was higher than that in spinal cord injury group and low-intensity exercise group at 28 days after treadmill training(P<0.05).(2)Compared with the control group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of epidermal growth factor receptor and EdU positive cells was increased in low-,moderate-,and high-intensity exercise groups(P<0.05),and the highest was found in moderate-intensity exercise group.Compared with control group,the proportion of glial fibrillary acidic protein positive cells was increased in spinal cord injury group(P<0.05).Compared with spinal cord injury group,the proportion of glial fibrillary acidic protein positive cells was lower in low-,moderate-,and high-intensity exercise groups(P<0.05),and the moderate-intensity exercise group was the lowest.(3)Hematoxylin-eosin staining showed that a large cavity was formed in the injured area of mice with spinal cord injury,and the cavity in the injured area of mice with spinal cord injury decreased after different intensities of treadmill training,and the decrease was most obvious in the moderate-intensity exercise group.(4)These results indicate that low-,moderate-,and high-intensity treadmill training can promote the recovery of motor function of mice with spinal cord injury by activating endogenous neural stem cells,and the effect of moderate-intensity exercise training is the most obvious.

BACKGROUND:We have successfully isolated and cultured neonatal mouse cerebrospinal fluid-contacting neurons in vitro,but there is no study that reports an effective method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons.There is no study on whether the self-renewal ability of cerebrospinal fluid-contacting neurons changes with age.OBJECTIVE:To establish a method for isolating and culturing high-purity adult mouse cerebrospinal fluid-contacting neurons in vitro,and to characterize the self-renewal ability of adult mouse cerebrospinal fluid-contacting neurons and neonatal mouse cerebrospinal fluid-contacting neurons in vitro.METHODS:Primary cells containing cerebrospinal fluid-contacting neurons were isolated from the cervical medulla of adult mouse (3 months of age) in adherent culture and transfected with lentivirus fused with multimodal imaging genes.High-purity adult mouse cerebrospinal fluid-contacting neurons were obtained by puromycin screening in suspension culture in complete medium.The expression of neural stem cell markers Nestin and SOX2 was detected by immunofluorescence in adult mouse cerebrospinal fluid-contacting neurons,and the ability of adult mouse cerebrospinal fluid-contacting neurons to form spheres and pass on in vitro was observed.An equal number (5×103/mL) of passage 3 adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons were divided into two groups under the same conditions and inoculated into ultra-low adhesion plates containing complete medium in suspension culture at 5％ CO2,37℃ thermostat,respectively.The self-renewal capacity of adult mouse and neonatal mouse cerebrospinal fluid-contacting neurons was characterized by in vitro spheroid formation,CCK8 assay,qPCR,and western blot assay.RESULTS AND CONCLUSION:(1) High-purity cerebrospinal fluid-contacting neurons were successfully isolated from adult mouse,which expressed Nestin and SOX2 in vitro,and were able to form neurospheres and pass on continuously.(2) The in vitro self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse,and the neurospheres formed by day 4 of cell culture in neonatal mouse were about 150 μm in diameter,whereas the neurospheres formed by adult mouse tactile neurons were only 40 μm in diameter (P<0.0001).(3) CCK8 proliferation assay showed that the proliferative activity of adult mouse cerebrospinal fluid-contacting neurons was significantly weaker than that of neonatal mouse at all time points after culture (P<0.0001).(4) qPCR and western blot assay revealed that the mRNA (P<0.0001) and protein expression levels (P<0.01) of Nestin and SOX2 in cerebrospinal fluid-contacting neurons of adult mouse were significantly decreased compared with those of neonatal mouse.(5) The above results indicated that the self-renewal ability of cerebrospinal fluid-contacting neurons in adult mouse was significantly weaker than that of neonatal mouse in vitro.

Objective:To describes the probability and rate of native liver survival (NLS) in biliary atresia (BA) patients after Kasai portoenterostomy (KPE)over various time periods and analyzes the perioperative factors associated with liver transplantation or death.Methods:A retrospective case-summary.BA patients administrated at the Department of Fetal and Neonatal Surgery in Hunan Children′s Hospital between January 2015 and December 2021.Probability and rate of NLS were calculated by life table.Cox proportional hazards regression model and Logistic model was applied to explore the perioperative factors related to post-Kasai liver transplantation/death.Results:The median age at Kasai surgery was 62 days.The rate of jaundice clearance (JC) was 64.5% within 3 months after Kasai, and 58.3% of the patients had cholangitis.The probability of NLS reached its lowest point in the first 1 year after Kasai (76.2%) and ranged from 93.2% to 98.0% in years 2-8 after Kasai.The rates of NLS in 2 years, 5 years and 8 years were 71.1%, 62.8% and 56.0%, respectively.Cytomegalovirus (CMV) infection before or on the day of Kasai without antiviral treatment can increase the risk of liver transplantation or death[ HR(95% CI): 1.628 (1.081-2.452), P=0.020].Preoperative gamma-glutamyl transferase increased the risk of liver transplantation/death within 1 year after Kasai[ OR(95% CI): 1.001 (1.000-1.001), P=0.021], and early cholangitis was a risk factor for liver transplantation/death within 5 years after Kasai[ OR(95% CI): 1.934 (1.004-3.726), P=0.048].JC within 3 months post-KPE was a protective factor of NLS. Conclusions:The first year after Kasai was the highest risk period for liver transplantation/death, which should be the focus of follow-up management.JC within 3 months after surgery is the protective factor for overall NLS, 1-year NLS and 5-year NLS.

Objective:To observe the therapeutic effect of moxibustion on rats with acute diarrhea; To explore its potential mechanism in protecting the intestinal mucosal barrier.Methods:Totally 40 SD rats were divided into four groups: normal group, model group, moxibustion group, and montmorillonite powder group according to random number table method, with 10 rats in each group. Except for the normal group, the remaining groups were established as acute diarrhea models using senna leaf decoction administered via gavage combined with cold stimulation. The moxibustion group received suspended moxibustion on bilateral "Tianshu"(Point ST25) and "Shangjuxu"(Point ST37) acupoints, while the montmorillonite powder group was administered 0.81 g/kg of montmorillonite powder via gavage. The normal and model groups received an equal volume of normal saline via gavage, once daily for 7 consecutive days. The diarrhea status of the rats was observed, and the loose stool rate and diarrhea index were calculated. HE staining was used to observe pathological damage to the colonic mucosa. ELISA was employed to measure serum diamine oxidase (DAO) and D-lactate levels. Immunohistochemical staining was used to detect the expressions of colonic tight junction proteins (Occludin) and cytoplasmic tight junction protein 1 (ZO-1). Chemiluminescence was used to measure adenosine triphosphate (ATP) and reactive oxygen species (ROS) levels in the colon. Transmission electron microscopy was used to observe changes in mitochondrial morphology in colonic mucosal cells. Western blot was used to detect the protein expressions of adenosine nucleotide translocator 2 (ANT2), cyclophilin D, and voltage-dependent anion channel 2 (VDAC2) in the colon.Results:Compared with the model group, the moxibustion and montmorillonite powder groups showed decreased loose stool rate, diarrhea index, and serum DAO and D-lactate levels ( P<0.05); the length of colonic mucosal villi increased ( P<0.05), while crypt depth decreased ( P<0.05); the protein expressions of colonic mucosal Occludin and ZO-1 increased ( P<0.05), ATP content increased ( P<0.05), ROS content decreased ( P<0.05), and the protein expressions of colonic mucosal ANT2, cyclophilin D, and VDAC2 decreased ( P<0.05). Conclusion:Moxibustion can improve acute diarrhea in rats and protect the intestinal barrier, and its mechanism may be related to the inhibition of the mitochondrial ANT2/mPTP pathway.

Objective To investigate the therapeutic effects and mechanism of quercetin in the treatment of periodontitis.Methods The rat periodontitis model was induced using ligation combined with lipopolysaccharide(LPS)injection method.Fifty successfully modeled periodontitis rats were randomly divided into 5 groups:the model group,the quercetin group(100 mg/kg quercetin by oral gavage),the quercetin+fibroblast growth factor receptor 1(FGFR1)overexpression plasmid(AV-FGFR1)group[100 mg/kg quercetin by oral gavage+10 nmol AV-FGFR1 via tail vein injection],the AV-FGFR1 group(10 nmol FGFR1 overexpression plasmids via tail vein injection),and the AV-NC group(10 nmol empty plasmids via tail vein injection),with 10 rats in each group.The normal group(10 rats)received the same volume of saline by oral gavage.After treatment completion,alveolar bone loss was observed by Micro-CT,periodontal tissue damage was observed by hematoxylin-eosin(HE)staining,serum levels of tumor necrosis factor(TNF)-α,interleukin(IL)-1β,and IL-18 were measured by enzyme-linked immunosorbent assay(ELISA),the proportion of FGFR1-positive cells in periodontal tissues was detected by immunohistochemistry,and protein expression levels of the FGFR1/Toll-like receptor 4(TLR4)/NLRP3 inflammasome pathway were analyzed by Western Blot.Results Compared with the normal group,the model group and AV-FGFR1 group showed significantly decreased bone mineral density(BMD)and bone volume/tissue volume(BV/TV),while serum TNF-α,IL-1β,IL-18 levels,the proportion levels of FGFR1-positive cells,and protein expression levels of FGFR1,TLR4,NF-κB p65,NLRP3,apoptosis-associated speck-like protein(ASC),and cleaved cysteinyl aspartate specific proteinase caspase-1(C-caspase-1)were increased,with statistical significance(P＜0.05).The AV-FGFR1 group exhibited more obvious decrease or increase effects.Administration of quercetin significantly improved these indexes in the model group.However,the therapeutic effects of quercetin were weakened after FGFR1 overexpression.Conclusion Quercetin can repair alveolar bone loss,ameliorate histopathological damage,and alleviate inflammatory injury in periodontitis rats,which may be mediated through inhibition of the FGFR1/TLR4/NLRP3 inflammasome pathway.

Objective To evaluate the clinical efficacy and safety of topical Zhikang Capsules(composed of Rhei Radix et Rhizoma,Coptidis Rhizoma,Notoginseng Radix et Rhizoma,Angelicae Dahuricae Radix,Asini Corii Colla,calcined Os Draconis,Bletillae Rhizoma,Myrrha,Endoconcha Sepiae,Rubia Radix et Rhizomae,Resina Draconis,etc.)in treating patients with risk of bleeding after operation for high perianal abscess.Methods The observation was conducted in 120 patients who took long-term oral use of Aspirin Enteric-Coated Tablets due to suffering from chronic stable angina and underwent operation for high perianal abscess in The Second Affiliated Hospital of Kunming Medical University from January 2024 to December 2024.The patients were divided into a control group and a treatment group using a randomized number table,with 60 cases in each group.The control group received postoperative topical Batracimab,while the treatment group received topical Zhikang Capsules.Both groups underwent a 7-day treatment course.Changes in the wound bleeding scores on postoperative days 2,4,and 6 in the two groups were observed.The scores of anal pain,perianal congestion and swelling,and wound exudate on postoperative day 5 were compared between the two groups.After treatment,the safety of both regimens was evaluated.Results(1)Scores of wound bleeding in both groups were decreased significantly on postoperative day 4 compared to postoperative day 2(P＜0.05 or P＜0.01),and were further decreased on postoperative day 6 compared to postoperative day 4(P＜0.01).However,no significant differences were observed between the two groups on postoperative days 2,4,or 6(P＞0.05).(2)The treatment group exhibited significantly lower scores of anal pain,perianal congestion and swelling,and wound exudate than the control group on postoperative day 5(P＜0.05 or P＜0.01).(3)The mean time for would healing in the treatment group was(16.821±1.793)days,significantly shorter than that in the control group(18.114±2.632)days,and the difference was significant(P＜0.05).(4)No significant adverse reactions occurred in either group during treatment,indicating a high safety profile.Conclusion Topical Zhikang Capsules demonstrate definite therapeutic efficacy and safety for patients complicated with risk of bleeding after operation for high perianal abscess,and exert stronger effects than Batracimab on alleviating anal pain,perianal swelling and wound exudate,and on accelerating wound healing.

Purpose To quantitatively compare the diffusion parameters of mono-and biexponential diffusion-weighted imaging models,and to obtain optimal sets of b-values in diffusion-weighted MRI for obtaining monoexponential apparent diffusion coefficient(ADC)close to perfusion-insensitive intravoxel incoherent motion(IVIM)model ADC(ADCIVIM)in identifying of pulmonary solid benign and malignant lesions.Materials and Methods IVIM was performed in 40 patients with solid nodule and masse in Xi'an Gaoxin Hospital from July 2021 to August 2022 using a 3.0T MR imager.Two experienced diagnostic radiologists subjectively evaluated the IVIM images.A single index model was used to calculate ADC values(ADC0-1 000,ADC20-1 000,ADC50-1 000,ADC80-1 000,ADC150-1 000,ADC300-1 000,ADC500-1 000,ADC300,500,1 000,ADC300,800,1 000,ADC300,500,ADC300,800 and ADC300,1 000).The reference standard ADCIVIM value were calculated using a double-exponential model.The physician's measurements between two physicians were measured.The malignant and benign groups were compared and receiver operator characteristic curve for all parameters were analyzed.Results The measurement consistency of ADC values under b value sets and ADCIVIM was very good,and the intraclass correlation coefficient was more significant than 0.75.The differences between ADCIVIM and ADC values in each b group were statistically significant(t=-6.016--2.500,all P<0.05).The area under the curve(AUC)of ADCIVIM was the largest(0.906),with an optimal threshold of 1.271×10-3 mm2/s,a sensitivity of 80.0%and a specificity of 93.0%.The diagnostic efficacy close to ADCIVIM were ADC300,800(AUC=0.891),ADC50-1 000(AUC=0.827)and ADC300,800,1 000(AUC=0.795),respectively.The optimal threshold of ADC300,800 was 1.140×10-3 mm2/s,the sensitivity and specificity were 80.0%and 93.7%,respectively.Conclusion Combining b-values 300 s/mm2 and 800 s/mm2 is recommended as routine scanning parameters for identifying the insensitive monoexponential ADC between benign and malignant solid pulmonary lesions.

Objective To investigate the relationship between the early neutrophil-to-lymphocyte ratio(NLR)in peripheral blood,poor prognosis and early neurological deterioration(END)in patients with acute ischemic stroke(AIS)following intravenous thrombolysis treatment.Methods The retrospective study included 221 AIS patients who underwent intravenous thrombolysis therapy.Demographic information,medical history,clinical and imaging data were collected.Peripheral venous blood samples were drawn before treatment for routine blood tests,and NLR was calculated.The primary endpoint was poor prognosis or death at 3 months after onset,and the secondary endpoint was symptomatic intracranial hemorrhage(SICH)or END within 24 hours after thrombolysis.Logistic regression was used to analyze factors associated with the primary and secondary endpoint events.Receiver operating characteristic(ROC)curve analysis was performed to evaluate the predictive value of NLR for clinical outcomes.Results Logistic regression analysis revealed that female,hypertension,higher baseline NLR(OR=1.968,95%CI:1.516-2.555,P＜0.001)and NIHSS scores were independent risk factors for 3-month poor outcomes in AIS patients.Female,a history of stroke or transient ischemic attack(TIA),higher random blood glucose,elevated baseline NLR(OR=1.317,95%CI:1.028-1.688,P=0.030)and NIHSS scores were independent risk factors for 3-month mortality.Hypertension,elevated homocysteine,higher baseline NLR(OR=1.420,95%CI:1.180-1.709,P＜0.001)and NIHSS scores were independent risk factors for END.There was no significant difference in NLR level between the SICH group(n=5)and the non-SICH group(n=216).ROC curve analysis showed that baseline NLR had high predictive value for 3-month poor outcomes,3-month mortality and END in AIS patients,with AUCs of 0.748(95%CI:0.679-0.817),0.738(95%CI:0.622-0.853)and 0.730(95%CI:0.656-0.804),respectively.There was no predictive value for SICH.Patients in the high NLR group(NLR≥2.63,n=89)had significantly higher baseline NIHSS scores,random blood glucose levels and rates of hypertension,coronary artery disease,END,3-month poor outcomes and 3-month mortality compared to those in the low NLR group(NLR＜2.63,n=132).Conclusion Elevated baseline NLR is associated with the occurrence of END and 3-month poor outcomes in AIS patients following intravenous thrombolysis therapy,suggesting its potential as a biomarker for predicting clinical outcomes in AIS patients.