This study was to study the effect of cyclosporine A (CsA) on the expression of nitric oxide synthase (NOS) in liver cells in T cell dependent liver injury induced by concanavalin A (ConA) in mice. The results showed that there was no NOS expression in the normal murine hepatocytes. Affer ConA challenge, the expression of NOS in hepatocytes increased markedly.Moreover, the hepatocytes closer to the central vein showed stronger expression.After pretreatment of CsA, activation of T lymphocytes was inhibited and NOS expression in the hepatocytes was almost completely inhibited too.The above results suggest that an upregulation of NOS expression might be a protective response to insufficient supply of blood and oxygen as a result of ConA induced liver injury, and inhibition of the NOS expression by CsA might be associated with inactivation of T lymphocyte.

BACKGROUND:Adipose-derived stem cels are regarded as the potential seed cels for tissue engineering. Colagenase digestion is used to isolate adipose-derived stem cels from fat pads currently. However, there are some problems, such as cumbersome operation and high cost.
OBJECTIVE: To study the basic biological characteristics of adipose-derived stem cels by tissue explants culture and to explore the differentiation potential into osteoblasts, adipocytes and endothelial progenitor cels in vitro.
METHODS:Adipose-derived stem cels were isolated by tissue explants technique from the bilateral groin fat pads of rats under aseptic conditions, and cultured in vitro. Cel counting kit-8 was used to detect the proliferative activity, and flow cytometry was employed to analyze the expression of cel surface markers. Passage 4 adipose-derived stem cels were cultured in osteogenic medium, adipogenic medium and endothelial progenitor cel medium for 2-3 weeks, and then the cels were identified.
RESULTS AND CONCLUSION:Adipose-derived stem cels that were isolated by tissue explants culture were easily cultured, and after subculture, cels were mainly spindle-shaped and grew in clone-like manner with swirling arrangement. Cels that experienced repeated subcultures stil kept stronger proliferative ability and the cel growth curve was shaped as a parabola. Immunochemical staining analysis revealed that adipose-derived stem cels were positive for CD44, CD90 and CD29, but negative for CD31, CD45. After adipogenic/osteogenic induction, the cels were respectively positive for oil red O staining and alizarin red staining. Induced endothelial progenitor cels were identified with CD34 and the ability to uptake Dil-ac-LDL and FITC-UEA. These findings indicate using the using tissue explants culture, high-purity adipose-derived stem cels easy to proliferate can be harvested, highly express stem cels-related antigens, and have the ability to differentiate into osteoblasts, adipocytes and endothelial progenitor cels, which meet the needs of seed cels in tissue engineering research.

OBJECTIVETo compare the impacts of percutaneous coronary intervention (PCI) and medical therapy on mortality in patients with stable coronary artery disease.

METHODSWe searched PubMed,Embase, Cochrane central register of controlled trials, Wanfang data and CNKI to find relevant randomized controlled trials on PCI versus medical therapy for treating patients with stable coronary artery disease, which were reported before December 2013. Publications were selected according to inclusion and exclusion standard. Meta-analyses was performed with the software of STATA 12.0.

RESULTSFive randomized controlled trials and 5 567 patients were enrolled for this analysis. Compared with medical therapy, PCI could not significantly decrease the long-term all-cause mortality (RR = 0.96, 95%CI 0.80-1.15), the cardiac death rate (RR = 1.02, 95%CI 0.77-1.36), the myocardial infarction rate (RR = 1.05, 95%CI 0.89-1.23), the acute coronary syndrome (RR = 0.70, 95%CI 0.27-1.82), the rate of freedom from angina (RR = 1.09, 95%CI 0.98-1.21), and the rate of stroke (RR = 1.27, 95%CI 0.75-2.15).However, the revascularization rate was significantly lower for patients in PCI group (RR = 0.60, 95%CI 0.42-0.86).

CONCLUSIONSLong-term mortality is similar for patients with stable coronary artery disease underwent PCI or medical therapy.

Angina Pectoris ; Coronary Artery Disease ; mortality ; therapy ; Coronary Disease ; Humans ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Randomized Controlled Trials as Topic ; Stroke

OBJECTIVETo evaluate the long-term outcomes of coronary artery disease patients with left main stem and/or multi-vessel disease receiving percutaneous coronary intervention (PCI) or coronary artery bypass graft(CABG).

METHODSPubMed, EMBase, Cochrane central register of controlled trials were searched to identify randomized controlled trials concerning the long-term outcomes of PCI and CABG in coronary artery disease patients with left main stem and/or multi-vessel disease before May 2013.Keywords included "angioplasty", "coronary", "coronary artery bypass surgery" and "stent". The data were analyzed by STATA 12.0.

RESULTSSix randomized controlled trials (5 071 patients) were enrolled for analyses.Five years all-cause mortality (RR = 1.13, 95% CI: 0.88-1.44, P = 0.35), incidence of myocardial infarction (RR = 1.20, 95% CI: 0.69-2.07, P = 0.53), and angina (RR = 1.17, 95% CI: 0.88-1.57, P = 0.28) were similar between PCI and CABG groups. Major adverse cardiac and cerebrovascular event (RR = 1.85, 95% CI: 1.38-2.48, P < 0.01) and repeat revascularization (RR = 3.48, 95% CI: 2.20-5.53, P < 0.01) were significantly higher in PCI compared to CABG.

CONCLUSIONSThe present analysis suggests that 5 years all-cause mortality is similar between PCI and CABG strategies.However, PCI is associated with higher major adverse cardiac and cerebrovascular event and repeat revascularization rate compared to CABG in patients with unprotected left main stem and/or multi-vessel disease.

Coronary Artery Bypass ; Coronary Artery Disease ; mortality ; surgery ; Humans ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention ; Randomized Controlled Trials as Topic ; Stents ; Treatment Outcome

Objective:To explore the association between different feeding patterns, emotional states, and salivary oxytocin (OT) levels during breastfeeding.Methods:From January to December 2019, 153 pairs of 3-month-old infants and their mothers were recruited from 4 maternal and child health hospitals in Chongqing, Liuzhou, Dalian and Hangzhou in China.Saliva samples were collected from the mothers at the first 5 minutes of feeding, 5 minutes during feeding, and 10 minutes after feeding.Edinburgh postnatal depression scale (EPDS) was used to evaluate maternal depression.Infants were divided into exclusive breastfeeding group and artificial feeding group according to feeding patterns.ELISA of salivary oxytocin was performed by ELISA kits, and the OT levels measured at the 3 time points were converted using linear interpolation.Area under the curve with respect to ground(OTAUCG) was used to represent the total concentration of salivary OT during the mother's breastfeeding.SPSS 25.0 software was used for statistical analysis.Multiple linear regression analysis and two factors analysis of variance were used to explore the association between different feeding methods, emotional state and salivary oxytocin during breastfeeding.Results:The results of the two factors analysis of variance showed that the interaction between feeding pattern and mother's emotion was not significant ( F=2.440, P=0.120), the main effect of mother's emotion was not significant ( F=0.380, P=0.539), and the main effect of feeding style was significant ( F=3.350, P=0.021). The level of OTAUCG under pure breastfeeding ((151 561.47±75 738.11) pg/mL) was higher than that under artificial feeding ((122 269.03±65 029.88) pg/mL), and the difference was statistically significant ( P=0.02). There was no statistically significant difference in OTAUCG levels between mothers with normal emotions ((146 106.37±75 106.76) pg/mL) and mothers with depressed emotions ((129 079.56±67 565.87) pg/mL) ( P=0.221). Multiple stepwise regression analysis showed that artificial feeding had a negative predictive effect on maternal salivary OT levels compared to exclusive breastfeeding( β=-0.211, t=-2.513, P=0.013). Conclusion:Feeding pattern is a factor that affects the mother's salivary OT level, and breastfeeding can improve the mother's OT level.

OBJECTIVE: To explore the correlation of the electric excitability treated with electroacupuncture (EA) at different acupoints and the prognosis of Bell's palsy, using the Logistic regression analysis. METHODS: A total of 93 patients of Bell's palsy were collected in the retrospective analysis. Acupuncture was applied to Cuanzu (BL 2), Yangbai (GB 14), Yingxiang (LI 20), Dicang (ST 4), Xiaguan (ST 7) and Qianzheng (Extra point) on the affected side. The electric stimulation was added at the three pairs of points, named Cuanzu (BL 2) and Yangbai (GB 14) (A group), Yingxiang (LI 20) and Dicang (ST 4) (B group) and Qianzheng (Extra point) and Xiaguan (ST 7) (C group), continue wave, 1 Hz at current frequency, for 30 min in one treatment. EA was given once every two days. The endpoint outcome evaluation was conducted when the facial nerve function was recovered completely after treatment or in 16 weeks after onset. On the 8th day of onset, the prognosis-related indexes were collected, such as the electric excitability grade in the A, B and C groups, gender, age, the facial nerve lesion segment and type 2 diabetes mellitus (T2DM). The Logistic regression analysis was conducted on these indexes and the prognosis. RESULTS: The single factor Logistic regression analysis showed that the gender, age and the electric excitability of the C group were negatively correlated with the prognosis statistically (>0.05). T2DM, the facial nerve lesion segment and the electric excitability of the A and B groups were positively correlated with the prognosis statistically (<0.05). The multivariate Logistic regression analysis indicated that the electric excitability in the A and B groups was the independent predictor of Bell's palsy prognosis (<0.05). values were 8.410 (1.176-60.113) and 12.589 (1.355-116.922) respectively. CONCLUSION The electric excitability of EA at the pairs of Cuanzu (BL 2) and Yangbai (GB 14), and of Yingxiang (LI 20) and Dicang (ST 4) is one of the indexes for the prognosis evaluation of Bell's palsy. It contributes to the early identification of the severity of facial nerve lesion, the regulation of the therapeutic regimen and the improvement of the clinical effects.
Acupuncture Points ; Bell Palsy ; therapy ; Diabetes Mellitus, Type 2 ; Electroacupuncture ; Facial Paralysis ; Humans ; Prognosis ; Retrospective Studies

Objective To explore the effect of 5-ethynyl-2'-deoxyuridine (EdU) -labeled adipose-derived stem cells (ADSCs) on lung colonization, TNF-α and IL-4 in rats induced by lipopolysaccharide (LPS) with acute lung injury. Methods Thirty male Sprague-Dawley (SD) rats were randomly divided into the normal control group (n=10), LPS model group (n=10), and LPS+ADSCs intervention group (n=10). The ALI model rats were intraperitoneally injected with 8 mg/kg LPS, rats in the normal control group were intraperitoneally injected with 4 mL/kg physiological saline, and rats in the LPS+ADSCs group were intravenously injected with 300 μL ADSCs by tail vein after 30 minutes for the ALI model establishment, and rats in the normal control group and LPS group were intravenously injected with 300μL physiological saline by tail vein. The time of death in rats was observed, lung tissue and blood from left ventricular were collected, and the serum tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-4) were detected by Enzyme-linked immunosorbent assay (ELISA). Lung wet/dry weight (W/D) ratio was detected by thoracotomy, the pathological changes of lung tissue were observed under optical microscope, and the colonization of ADSCs in the lungs were observed under immunofluorescence microscopy. LSD-t method was used to compare between every two groups. Results There was no significant difference in mortality between the LPS group and LPS + ADSCs group (50％ vs. 70％, P> 0.05); EdU-labeled ADSCs were extensively colonized in the lungs by tail vein injection after 24 h; Compared with the normal control group, the lung injury of the LPS group was heavier, the ratio of lung W/D and TNF-α were significantly increased (all P< 0.01), and IL-4 level was significantly decreased (P< 0.01). Compared with the LPS model group, the degree of lung injury in the LPS + ADSCs group was significantly reduced, lung W/D ratio (5.57±0.27 vs. 5.98±0.28) and TNF-α level of blood [(41.51±4.14)ng/L vs. (45.52±3.74)ng/L] were significantly reduced (all P< 0.05), whereas the IL-4 levels were significantly increased [(7.01±1.11)pg/mL vs. (3.27±0.54)pg/mL, P< 0.05]. Conclusions EdU-labeled ADSCs could be colonized in the lungs of LPS-induced ALI rats, reduce the inflammatory response from TNF-α and improve the anti-inflammatory response from IL-4.

Objective:To improve the therapeutic regimen for mantle cell lymphoma,we investigated the efficacy and safety of adding a BTK inhibitor to a regimen including rituximab,bendamustine,cytarabine,and prednisone to treat patients with mantle cell lymphoma(MCL).Methods:Twenty-six patients newly diagnosed with MCL who were admitted to The First Affiliated Hospital of Zhengzhou University from March 2021 to November 2023 were treated with a regimen of rituximab,bendamustine,cytarabine and prednisone combined with a BTK inhibitor,and the efficacy and adverse effects of this regiment were retrospectively analyzed.Results:The median age of the 26 newly dia-gnosed MCL patients was 59(41-72)years.The cohort included 22 males and 4 females,and the median follow-up time was 12(3-28)months.The overall response rate(ORR)was 92.3%and the complete response rate(CRR)was 88.5%.Median progression-free survival(PFS)and median overall survival(OS)endpoints were not achieved,with a 1-year PFS rate of 81.25%and a 1-year OS rate of 92.3%.A bet-ter PFS was achieved in the low mantle cell lymphoma International Prognostic Index(MIPI)score(0-3 points)group than in the high MIPI score(4-11 points)group(P=0.020).PFS was better in the group without B symptoms than in the group with B symptoms(P=0.002).PFS was better in the classical group than in the pleomorphic-blastoid subtype group(P=0.009).The main adverse effects were lymphopenia and thrombocytopenia.No treatment-related serious adverse events were observed during the follow-up period.Conclusions:The regimen of rituximab,bendamustine,cytarabine,and prednisone in combination with BTK inhibitors is safe and effective for the treatment of newly dia-gnosed patients with MCL.

Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.

ObjectiveTo investigate the therapeutic effect of the water extract of Zanthoxylum bungeanum aqueous extract（ZBAE）on rheumatoid arthritis. MethodThe sixty SD rats were divided into normal group， model group ［complete Freund's adjuvant （CFA）， 10 mg·kg^-1］， methotrexate（MTX） group （0.25 mg·kg^-1）， low -， medium -， and high-dose ZBAE groups （90， 180， 360 mg·kg^-1）. The rats in MTX group were given intraperitoneal injection for two weeks， three times a week， and the rats in ZBAE group were administrated for 14 days. The swelling of the ankle joint and body weight were observed， and arthritis scores were also performed. Computed tomography （CT）， hematoxylin-eosin （HE） staining and safranine-O and fast green staining were used to observe the effect of ZBAE on synovial hyperplasia and bone protection. Cell counting kit-8（CCK-8）method was used to detect the proliferation of the RA-FLSs cells treated with ZBAE. According to the results of CCK-8 experiment， the optimal concentration and time of administration were determined， blank group， low -， medium -， and high-dose ZBAE groups （0.08，0.10，0.12 g·L^-1） were set up. The cell cycle distribution and apoptosis rate were analyzed by flow cytometry，the migration ability of RA-FLSs cells was examined by scratch test. Western blot was used to detect the effect of ZBAE on phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， cyclin-dependent kinase 2 （CDK2）， Cyclin A and phosphorylated PI3K， Akt （p-PI3K，p-Akt） protein expression in RA-FLSs cells. ResultCompared with the normal group，joint swelling index and arthritis score were increased in the model group （P<0.05），the bone of the ankle was seriously damaged， and there was obvious synovial hyperplasia. Compared with the model group， the ZBAE group could significantly reduce the joint swelling index （P<0.05）， inhibit synovial hyperplasia and cartilage destruction. In vitro study showed that compared with the blank group， ZBAE could inhibit the migration of RA-FLSs （P<0.05）， promoted cell apoptosis （P<0.05）， and acted on RA-FLSs cells in S phase to inhibit cell proliferation. Moreover， the result of Western blot showed that compared with the blank group， the expression of p-PI3K， p-Akt， CDK2 and Cyclin A proteins were significantly decreased in the high dose group of ZBAE （P<0.05）. ConclusionThese results suggest that ZBAE has a therapeutic effect on rheumatoid arthritis by inhibiting synovial hyperplasia， promoting synovial apoptosis and inhibiting its migration.