Aim To investigate the protective effects of co-administered piperine on reversing the skeletal deterioration induced by fluoxetine.Methods Female ovariectomized rats were orally administered with estra-diol,fluoxetine,piperine and the mixture of piperine and fluoxetine for eight weeks,respectively.X-ray ab-sorption assay was used to determine bone mineral den-sity(BMD).microCT was used to analyze the effects of drug treatments on micro-architecture,three-bending test was performed to examine the biomechanical prop-erties.ELISA kits were employed to quantify the bone turnover markers in serum.Besides,rat primary osteo-blasts were cultured to investigate the osteoblastogene-sis and mineralization in the presence of fluoxetine with or without piperine.Results Compared with ovariec-tomized rats,the administration of estradiol and piper-ine significantly enhanced BMD and biomechanical properties with improved micro-architecture of trabecu-lar bones.Fluoxetine treatment further deteriorated BMD,biomechanical properties and micro-architecture of ovariectomized rats with accelerated bone turnover.Concomitant administration of piperine with fluoxetine significantly suppressed the deteriorating effects on skeleton by fluoxetine.In addition,fluoxetine reduced the differentiation and mineralization of primary osteo-blasts,whereas combined therapy showed promotional effects.Conclusions The administration of fluoxetine induces further bone loss in ovariectomized rats by in-hibiting osteoblastic differentiation and mineralization.The co-administration of piperine with fluoxetine rever-ses its skeletal deterioration.

Objective To explore medium and long term efficacy of oblique lateral interbody fusion(OLIF)in treating lumbar specific infection.Methods From October 2017 to January 2021,24 patients with lumbar specific infection were treated by OLIF combined with vertebral screw internal fixation,including 15 males and 9 females,aged from 27 to 61 years old with an average of(43.0±15.0)years old;the courses of disease ranged from 6 to 24 months with an average of(14.0±7.0)months;7 patients with L2-L3,12 patients with L3-L4 and 5 patients with L4-L5;19 patients with tuberculosis infection and 5 patients with brucella infection.The amount of intraoperative blood loss,operative time and complications were recorded,and erythro-cyte sedimentation rate(ESR),C-reactive protein(CRP),visual analogue scale(VAS),Japanese Orthopaedic Association(JOA)score and American Spinal Injury Association(ASIA)rating were compared before and one month after opertaion.Re-sults All patients were followed up from 9 to 24 months with an average of(13.0±6.0)months.Operative time was(132.5±21.4)min,and intraoperative blood loss was(227.3±43.1)ml.ESR and CRP were decreased from(82.34±18.62)mmol·h-1 and(53.08±21.84)mg·L-1 before operation to(33.52±17.31)mmol·h-1 and(15.48±8.36)mg·L-1 at one month after opera-tion,respectively(P＜0.05).VAS was decreased from(7.52±1.36)before opertaion to(1.74±0.87)at one month after opera-tion(P＜0.05).JOA was increased from(17.86±3.95)before operation to(24.72±3.19)at one month after operation(P＜0.05).Four patients had neurological symptoms before operation,and were classified to grade D according to ASIA classifica-tion,who were recovered to grade E at 1 month after operation.One patient was suffered from psoas major muscle injury after operation,and returned to normal at 3 weeks.One patient was suffered from abdominal distension and difficulty in defecation,and relieved after gastrointestinal decompression and enema.No complications such as abdominal organ injury and poor wound healing occurred in all patients.Conclusion OLIF combined with vertebral screw internal fixation is a new minimally invasive surgical method for the treatment of lumbar specific infection,especially the lesion located on the middle lumbar vertebra.It has advantages of less trauma,short operation time,less blood loss,convenient operation,complete removal of the lesion,safety and effectiveness,and has good medium-and long-term efficacy for lumbar specific infection.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

AIM:This study aims to explore the impact of Escherichia coli(E.coli)high-pathogenicity island(HPI)on pyroptosis and intestinal inflammation.METHODS:Kunming mice and IPEC-J2 cells(porcine small intesti-nal epithelial cells)were treated with HPI-containing E.coli strain(HPI+),HPI-deleting E.coli strain(ΔHPI),or lipo-polysaccharide(LPS).The intestinal lactate dehydrogenase(LDH)activity,superoxide dismutase(SOD)activity,IgA expression and secretory IgA(SIgA)content were assessed in mice.The expression of key regulatory factors in the nucleo-tide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1 signaling pathway-related proteins in mouse intestinal tract and IPEC-J2 cells was analyzed by RT-qPCR,immunohistochemical staining and Western blot.The levels of interleukin-1β(IL-1β)and IL-18 in mouse serum and IPEC-J2 cell culture supernatants were measured by ELISA.The pivotal role of NLRP3 in HPI+infection was confirmed by silencing NLRP3 in IPEC-J2 cells using siRNA.RE-SULTS:The HPI+infection markedly decreased SOD activity,increased IgA+B cell count,and induced the LDH release and SIgA secretion in the mouse intestine compared with ΔHPI infection.The results of ELISA,HE staining and TUNEL staining indicated that E.coli HPI triggered DNA damage,tissue injury and inflammation in mouse intestinal epithelial cells.Western blot revealed an increase in intestinal gasdermin D N-terminal fragment(GSDMD-N)protein level with HPI+infection compared with ΔHPI infection.E.coli HPI significantly up-regulated mRNA and protein expression of NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,GSDMD,IL-1β and IL-18 in mouse intestinal tissues and IPEC-J2 cells,accompanied by the elevated secretion of IL-1β and IL-18.The confo-cal microscopy demonstrated an enhanced assembly of the NLRP3 inflammasome with HPI+infection compared with ΔHPI infection,leading to colocalization of NLRP3 and caspase-1.Furthermore,NLRP3 silencing in IPEC-J2 cells attenuated E.coli HPI-induced cell inflammation,damage,and NLRP3/caspase-1 signaling pathway activation.CONCLUSION:The presence of HPI enhances the virulence of E.coli and exacerbates intestinal inflammation.Moreover,pyroptosis,regu-lated by the NLRP3/caspase-1 signaling pathway,plays a pivotal role in the intestinal injury induced by E.coli HPI.

Objective To study the protective effect of Irisin in doxorubicin(Dox)induced-Cardiomyopathy and its possible mechanism.Methods AC 16 cells were used to construct Dox injury model and divided into control group(AC 16 cells were cultured with complete medium),Irisin group(AC16 cells were treated with 10 ng·L-1 Irisin for 24 h),Dox group(AC 16 cells were treated with 4 μmol·L-1 Dox for 24 h),Dox+Irisin group(AC 16 cells were pretreated with 10 ng·L-1 Irisin for 2 h,and then treated with 4 pmol·L-1 Dox for 24 h).Cell counting kit-8(CCK-8),terminal deoxynucleotidyl transferase-mediated nick end labeling(TUNEL)and lactate dehydrogenase(LDH)were used to detect the proliferation,apoptosis and mortality of AC 16 cells.Western blot was used to detect the expression levels of nuclear factor-κB(NF-κB)signaling pathway and apoptotic factors B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax)and caspase-9 protein.Mito-Tracker Red CMXRos probe was used to detect mitochondrial membrane potential.Results In the contrl group,Irisin group,Dox group,Dox+Irisin group,the rate of apoptosis were(0.97±0.09)％,0,(42.80±6.70)％,(11.74±1.79)％;the expression of Bax protein were 0.85±0.01,0.36±0.02,1.15±0.07,0.37±0.11;the expression of caspase-9 protein were 0.52±0.02,0.59±0.03,1.11±0.02,0.67±0.08;the expression of Bcl-2 protein were 1.01±0.04,1.05±0.25,0.43±0.02 and 0.99±0.30;the probability of mitochondrial damage were(0.02±0.01)％,(0.5±0.15)％,(38.6±2.39)％,(1.58±0.54)％.The difference of the above indexes between the contrl group and the Dox group were statistically significant(all P＜0.05);the difference between Dox group and Dox+Irisin group were statisically significant(all P＜0.05).Conclusion Irisin could reduce the expression level of Bax,caspase-9,p-NF-κB,and p-mTOR caused by Dox,increase the expression level of Bcl-2,ameliorate the myocardial damage caused by Dox,and reduce cardiotoxicity.

Hormonal receptor positive human epidermal receptor 2 negative (HR⁺/HER2^-) is the commonest molecular subtype of breast cancer (BC). Patients with HR⁺/HER2^- BC may manifest clinically a late recurrence whose BC metastasizes 10-15 years post-operatively. We report one case who presented with pulmonary mass in upper lobe of lung and Horner syndrome 16 years after BC surgery. FDG PET/CT suggested pulmonary malignancy but could not differentiate between primary or metastatic cancer when invasive biopsy was quite risky. Novel ¹⁸F-FES PET/CT facilitated the non-invasive functional diagnosis of estrogen-receptor positive (ER+) pulmonary metastasis of BC, and the patient experienced partial response (PR) after CDK4/6 inhibitor and aromatase inhibitor as endocrine therapy. This article reviews the diagnosis and treatment process of this case, to provide guidance for non-invasive global evaluation of ER status among metastatic HR⁺/HER2^- BC patients with ¹⁸F-FES PET/CT.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

To investigate the value of self-developed air-free laparoscopic auxiliary instruments in the clinical application of thyroid diseases.The clinical data of 70 transaxillary and 45 transareolar air-free laparoscopic surgeries for thyroid cancer and 40 conventional open surgeries were retrospectively compared.The transaxillary and transareolar laparoscopic groups had significantly longer operative times than the open group,while the postoperative satisfaction was higher in the endoscopic group than in the open group.This set of instruments has advantage of novel design,scientific structure,safe application.It can be compatible with a variety of thyroid and breast air-free laparoscopic procedures,which can promote the development and popularization of laparoscopic technology.

Objective To investigate the clinical efficacy and safety of Zishen Jianpi Quyu Formula in treating patients with migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.Methods A total of 104 patients with migraine without aura of kidney deficiency and blood stasis type were randomly divided into the control group and the trial group,with 52 cases in each group.The control group was treated with Flunarizine Hydrochloride Capsules,and the trial group was treated with Zishen Jianpi Quyu Formula on the basis of treatment for the control group.One menstrual cycle constituted a course of treatment,and the treatment covered a total of two courses(eight weeks).The changes of traditional Chinese medicine(TCM)syndrome score,migraine attack frequency,duration of migraine headaches,visual analogue scale(VAS)score of migraine headache intensity,Headache Impact Test-6(HIT-6)score and hemorheology indexes in the two groups before and after treatment were observed.Moreover,the efficacy for TCM syndrome and clinical safety in the two groups were evaluated.Results(1)After two courses of treatment,the total effective rate of the trial group was 90.38%(47/52),and that of the control group was 69.23%(36/52),the intergroup comparison(by chi-square test)showed that the efficacy for TCM syndrome in the trial group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores of the patients in both groups were significantly lower than those before treatment(P＜0.05),and the reduction of TCM syndrome score in the trial group was significantly superior to that in the control group(P＜0.05).(3)After treatment,the migraine attack frequency,duration of migraine headaches,VAS scores of migraine headache intensity in the two groups of patients were significantly improved compared with those before treatment(P＜0.05),and the improvement of migraine headache parameters in the trial group was significantly superior to that in the control group(P＜0.05).(4)After treatment,the HIT-6 score in the two groups was decreased significantly compared with those before treatment(P＜0.05),and the decrease of HIT-6 score in the trial group was significantly superior to that in the control group(P＜0.05).(5)After treatment,hemorheology indexes(including plasma viscosity,whole blood high-shear viscosity,whole blood low-shear viscosity,fibrinogen,and hematocrit)in the two groups were improved compared with those before treatment(P＜0.05),and the improvement of each of hemorheology indexes in the trial group was significantly superior to that in the control group(P＜0.05).(6)During treatment,no serious adverse events occurred in the two groups,which was of high safety.Conclusion Zishen Jianpi Quyu Formula exerts remarkable clinical efficacy in treating patients of migraine without aura in the postmenstrual period of kidney deficiency and blood stasis type.The formula is effective on improving the TCM syndromes and migraine attacks of the patients,achieving the efficacy of milder headache,lower attack frequency and shorter duration,more stability hemorheology indexes and higher safety.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.