Objective To investigate the beneficial effect of Kai-Xin-San combined with fluoxetine in improving depression-like behaviors on chronic unpredictable mild stress(CUMS)induced depression model mice.Methods The present study aimed to assess the potential of Kai-Xin-San in combination with fluoxetine to ameliorate depression-like behaviors in a CUMS induced mouse depression model.Behavioral tests,such as the sucrose preference test were employed to evaluate the efficacy of the treatment.Additionally,the levels of suppressed stress factors were measured using the ELISA method.The morphology of hippocampal tissue was evaluated using the HE staining method,Nissl Staining and TUNEL staining methods.Furthermore,western blotting analysis was utilized to determine the expression levels of proteins such as Caspase-3,and Caspase-9.Results The co-administration of Kai-Xin-San and fluoxetine resulted in a significant increase in sucrose preference rate in model mice.This effect was comparable to that of fluoxetine alone at the standard clinical dose.Furthermore,the combination treatment up-regulated the levels of suppressed stress factors,reduced the apoptosis of hippocampus induced by depression and regulated the apoptosis signaling pathway in hippocampus.Conclusion The combination of Kai-Xin-San and fluoxetine has been shown to be an effective treatment for depression-like behavior in animal models,resulting in a reduction in the required clinical dosage of fluoxetine.This effect may be attributed to the up-regulation of neurotransmitter expression,inhibition of stress axis activation,and central nervous inflammation.

Osteoarthritis(OA)is a chronic progressive osteoarthropathy in the elderly.Osteoclast activation plays a crucial role in the occurrence of subchondral bone loss in early OA.However,the specific mechanism of osteoclast differentiation in OA remains unclear.In our study,gene expression profiles related to OA disease progression and osteoclast activation were screened from the Gene Expression Omnibus(GEO)repository.GEO2R and Funrich analysis tools were employed to find differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses demonstrated that chemical carcinogenesis,reactive oxygen species(ROS),and response to oxidative stress were mainly involved in osteoclast differentiation in OA subchondral bone.Furthermore,fourteen DEGs that are associated with oxidative stress were identified.The first ranked differential gene,heme oxygenase 1(HMOX1),was selected for further validation.Related results showed that osteoclast activation in the pathogenesis of OA subchondral bone is accompanied by the downregulation of HMOX1.Carnosol was revealed to inhibit osteoclastogenesis by targeting HMOX1 and upregulating the expression of antioxidant protein in vitro.Meanwhile,carnosol was found to alleviate the severity of OA by inhibiting the activation of subchondral osteoclasts in vivo.Our research indicated that the activation of osteoclasts due to subchondral bone redox dysplasia may serve as a significant pathway for the advancement of OA.Targeting HMOX1 in subchondral osteoclasts may offer novel insights for the treatment of early OA.

Objective:To investigate the effect of preoperative use of diuretics on cardiac surgery-associated acute kidney injury(CSA-AKI)in elderly patients.Methods:In this single-center retrospective study, 1 638 patients aged ≥60 years and undergone cardiac surgery(including coronary artery bypass grafting, valve replacement and valvuloplasty)in the Department of Cardiovascular Surgery, Linyi People's Hospital between January 2015 and December 2022 were recruited.The last preoperative serum creatinine(SCr)level was taken as the baseline value, and AKI was diagnosed according to the Kidney Disease Improving Global Outcomes(KDIGO)criteria.Patients were divided into an AKI group and a non-AKI group according to whether AKI occurred after surgery.The clinical characteristics of the two groups were compared, and the effect of preoperative use of diuretics on CSA-AKI was evaluated by multivariate Logistic regression analysis.Results:Of 1638 patients enrolled in the study, 284 patients(17.3%)developed CSA-AKI.Compared with the non-AKI group, there were higher proportions of patients in the AKI group receiving furosemide(62.7% or 178/284 vs.46.2% or 626/1 354, χ2=25.397, P<0.001), spironolactone(70.1% or 199/284 vs.49.9% or 676/1 354, χ2=38.284, P<0.001), and hydrochlorothiazide(8.1% or 23/284 vs.3.5% or 47/1354, χ2=12.288, P<0.001). The number of diuretics in the AKI group was higher than in the non-AKI group[2(0, 2) vs.1(0, 2), Z=-6.381, P<0.001], and the proportion of patients using ≥2 diuretics was higher in the AKI group than in the non-AKI group(70.1% or 199/284 vs.49.0% or 664/1354, χ2=41.652, P<0.001). Multivariate Logistic regression analysis showed that, after adjusting for hypertension, diabetes mellitus, hypoalbuminemia, NYHA functional class Ⅲ/Ⅳ, cardiopulmonary bypass during surgery, operative duration≥6 h, postoperative blood transfusion>600 ml, postoperative use of >3 vasoactive drugs and other variables, preoperative use of ≥2 diuretics remained an independent risk factor for CSA-AKI in elderly patients( OR=1.580, 95% CI: 1.042-2.396, P=0.031). Conclusions:AKI is a common complication after cardiac surgery in elderly patients.Preoperative use of ≥2 diuretics used may be an independent risk factor for CSA-AKI.

Objective:To compare ultrasound (US) guided versus computed tomography (CT) guided radiofrequency ablation (RFA) in treatment of early hepatocellular carcinoma (HCC).Methods:The data of 133 patients with early HCC treated by RFA in the Department of Hepatobiliary Surgery of Shandong Provincial Hospital from February 1, 2015, to January 31, 2017, was analyzed retrospectively. These patients were divided into two groups: the US-guided group and the CT-guided group. The clinical data was collected and the factors affecting prognosis were analyzed.Results:Compared with the CT-guided group, the operation time of the US-guided group was significantly shorter [(29.0±12.0)min vs. (55.0±19.0)min, P<0.05], but the number of ablation sessions per tumor was significantly less [(1.1±0.3) vs. (2.0±0.6), P<0.05]. There was no significant difference in the complete ablation rates, postoperative complication rates and postoperative length of hospital stay between the two groups ( P>0.05). The CT-guided group was superior to the US-guided group in the local tumor recurrence and progression-free survival rates ( P<0.05). On multivariate analysis, CT-guided RFA was an independent protective factor for local tumor recurrence ( HR=0.266, 95% CI: 0.073-0.967, P<0.05) and progression-free survival ( HR=0.415. 95% CI: 0.213-0.806, P<0.05), while AFP >20 ng/ml ( HR=4.821, 95% CI: 1.714-13.560, P<0.05) was an independent risk factor for progression-free survival. Conclusion:CT-guided percutaneous RFA was superior to US-guided RFA in local treatment of early HCC, probably related to more needle placements and longer ablation time under CT guidance.

AIM: To investigate the clinical application value of trazodone combined with cognitive behavioral therapy on heroin addicts during the period of community detoxification. METHODS: A total of 140 heroin addictive patients treated by community detoxification management were randomly divided into four groups, 35 patients were given trazodone combined with cognitive behavioral therapy (T+P group), 35 patients were given a single trazodone therapy (T group), 35 patients were given a single cognitive behavioral therapy (P group), and 35 patients were only given community detoxification management (S group), the course of the treatment lasted for 12 weeks. At the time-point of baseline and the weekends 4, 8 and 12 after treatment, four groups were scored by Hamilton anxiety rating scale (HAMA), Hamilton depression rating scale (HAMD), Pittsburgh sleep quality index scale (PSQI), psychological craving rating scale (PCS), Chinese perceived stress scale (CPSS), and urine morphine positive rate. The safety was evaluated with Treatment Emergent Side-effect Scale (TESS) and laboratory test. RESULTS: A total of 125 patients completed the 12 weeks of treatment. HAMA, HAMD and PSQI scores of T+P group and T group on weekends 4, 8 and 12 were significantly reduced when compared with baseline, respectively (P< 0.05). HAMA and HAMD scores of P group on weekends 4, 8 and 12 were significantly decreased when compared with baseline, respectively (P< 0.05). PSQI scores of P group on weekends 8 and 12 were significantly decreased when compared with baseline, respectively (P< 0.05). HAMA, HAMD and PSQI scores of S group on weekend 12 were significantly reduced when compared with baseline, respectively (P< 0.05). There were significant differences on the PCS and CPSS scores between T+P group, T group, P group and S group on weekends 4, 8 and 12, respectively (P< 0.05). There also showed statistically significant differences on the urine morphine positive rates between T+P group and S group on weekends 4, 8 and 12, respectively (P< 0.05). There was no significant difference on the TESS score between T+P group and T group (P> 0.05). CONCLUSION: Trazolone combined with cognitive behavior therapy can significantly improve the negative emotions, sleep quality and other related mental symptom of heroin addiction patients in the community detoxification period, and play a positive role in improving the quality of community detoxification management.

Objective: To investigate the clinical effect of the reserve-flow anterolateral thigh perforator flap based on aesthetics concept to repair soft tissue defect around the knee joint. Methods: From June 2016 to April 2017, 10 patients with skin and soft tissue defects around the knee joint were admitted to Mingzhou Hospital of Zhejiang University. The area of the soft tissue defects around the ankle were ranged from 5.0 cm × 3.0 cm to 11.0 cm × 7.5 cm after debridement. The anterolateral thigh perforator flaps were designed on the ipsilateral lateral thigh, according to the results of preoperative perforator detection. The reserve-flow anterolateral thigh perforator flaps based on aesthetic concept were used to repair the wound through the subcutaneous tunnel. The flaps were 5.5 cm × 3.5 cm to 12.0 cm × 8.0 cm in size. The donor sites were directly closed. Results: The flaps of 9 patients completely survived, however, epidermal necrosis occurred to 1 patient, at the distal end of the flap, about 1 cm × 1 cm in size. It completely healed after dressing change for 1 week. The follow up time was from 8 to 15 months (mean 12 months). The flaps were satisfactory in appearance, good in the elasticity, nearly normal in color, and had protective sensation. The two-point discrimination perception ranged from 9 to 13 mm(mean 10 mm). The donor and recipient sites only remained linear scars, with no depression deformity. The lower limb functions were normal. Conclusions The reverse-flow anterolateral thigh flap based on aesthetic concept, is an alternative method to repair the soft tissue defect around the knee joint, and protect the donor site to the maximum extent.

Akt is the downstream target protein of phosphatidylinositol 3-kinase(PI3K),and PI3K/Akt signaling pathway is involved in cell proliferation,differentiation,apoptosis and metabolism.The activities of Akt in the central nervous system is also regulated by the neurotransmitter dopamine(DA),therefore Akt mediates multiple drug addiction process.This article reviews the structural characteristics and activity regulation of Akt,as well as the related research in drug addiction of this signal molecule.

Objective To study the role of serum Hcy level change in predicting the effects of pemetrexed (PEM ) chemotherapy for treating the patients with advanced lung adenocarcinoma .Methods Fifty‐seven cases of lung adenocarcinoma treated by the PEM chemotherapy were retrospectively analyzed .The fasting venous blood was collected for detecting serum Hcy level before chemotherapy and at the end of 2‐week chemotherapy .The clinical characteristics ,Hcy level before and after chemotherapy and the relation between the Hcy level with clinical effect were statistically analyzed .Results In the therapeutic effects evaluated by the im‐aging examination during treatment process ,there were no case of complete remission (CR) ,19 cases of partial remission (PR) ,22 cases of stable diseases(SD) and 16 cases of progressed diseases(PD) ,the objective response rate(ORR) was 33 .3% and disease control rate (DCR) was 71 .9% .Different clinical factors had no significant influence on the efficacy of PEM chemotherapy (P>0 .05) .In comparing the influence of Hcy level and Hcy level change on the effect of PEM chemotherapy ,the results showed that serum Hcy level before treatment had no obvious influence on curative effect ,DCR in the patients with normal serum Hcy level after treatment was significant higher than that with abnormal Hcy level ,ORR and DCR in the patients with decreased Hcy level after chemotherapy were significantly higher than those with increased Hcy level (P<0 .05) .Conclusion Monitoring the serum Hcy lev‐el change during the PEM chemotherapeutic process in the patients with advanced lung adenocarcinoma may be used in the predic‐tion of the chemotherapeutic effect .

OBJECTIVE To investigate the effect of injection of β2-adrenergic receptor agonist clenbuterol into the infralimbic cortex(IL) on drug-seeking behavior triggered by conditioned cues. METHODS Adult male SD rats were trained to self-administer heroin under a FR1 schedule for consecutive 14 d,followed by 2-h extinction training. Cue-induced heroin seeking was measured for 2 h. Clenbuterol was microinjected bilaterally into the IL(8 ng/side)of rats 15 min prior to reinstatement test. Meanwhile,locomotor activity was detected 15 min after clenbuterol or artifial cerebrospinal fluid(mod?el group) was microinjected bilaterally into IL. Western blotting was used to detect the expression of phosphorylated cyclic AMP response element-binding protein(p-CREB)in the prelimbic cortex(PL), IL,nucleus accumbens core (NACc) and shell (NACsh) of rats immediately after reinstatement test. RESULTS After heroin administration training for 14 consecutive days,these animals exhibited reliable heroin self-administration,indicated by the increase in active nose poke responses and infusions. The rats that had received infusion of clenbuterol into the IL had significantly lower active pokes (8 ± 3)than those in model group(45±10)in cue-induced reinstatement(P<0.01),but there was no significant differ?ence between clenbuterol group and vehicle group in the locomotor activity. The expression of p-CREB in either IL or NACsh was significantly decreased in clenbuterol group compared with model group(P<0.01,P<0.05),but significantly increased in NACc(P<0.01). CONCLUSION Microinjection of clenb?uterol into the IL can attenuate the cue-induced reinstatement of heroin-seeking behavior in rats. The underlying mechanism might be related to the regulation of p-CREB expression in the NACc and NACsh.