ObjectiveTo investigate the triglyceride-glucose (TyG) index and the level of serum homocysteine (Hcy) in association with the incidence of stroke in type 2 diabetes mellitus (T2DM) patients. MethodsBased on the chronic disease risk factor surveillance cohort in Pudong New Area, Shanghai, excluding those with stroke in baseline survey, T2DM patients who joined the cohort from January 2016 to October 2020 were selected as the research subjects. During the follow-up period, a total of 318 new-onset ischemic stroke patients were selected as the case group, and a total of 318 individuals matched by gender without stroke were selected as the control group. The Cox proportional hazards regression model was used to adjust for confounding factors and explore the serum TyG index and the Hcy biochemical indicator in association with the risk of stroke. ResultsThe Cox proportional hazards regression results showed that after adjusting for confounding factors, the risk of stroke in T2DM patients with 10 μmol·L⁻¹-¹ and Hcy>15 μmol·L⁻¹ was 1.532 times (95%CI: 1.017‒2.309 times, P=0.041) and 1.738 times (95%CI: 1.119‒2.699 times, P=0.014) higher respectively, compared to T2DM patients with Hcy≤10 μmol·L⁻¹. T2DM patients with TyG>9.074 had 1.396 times higher risk of stroke (95%CI: 1.091‒1.787, P=0.008) compared to those with TyG≤9.074. The study found that urea and α1-antitrypsin (α1-AT) were independent risk factors for the incidence of stroke in T2DM patients. For every unit increase in urea andα1-AT, the risk of stroke in T2DM patients increased by 233.6% (HR=3.336, 95%CI: 1.588‒7.009, P=0.001) and 11.3% (HR=1.113, 95%CI: 1.028‒1.205, P=0.008), respectively. Cumulative risk curves showed that Hcy>10 μmol·L⁻¹ and TyG>9.074 accelerated the time to stroke occurrence in T2DM patients. ConclusionElevated levels of Hcy>10 μmol·L⁻¹ and a higher TyG index are risk factors for stroke in T2DM patients. Effective interventions for Hcy and TyG should be conducted for diabetic patients to reduce the incidence of stroke.

Purpose: Invasive ductal carcinoma (IDC) accounts for 90% of triple-negative breast cancer (TNBC). IDC is mainly derived from the breast ductal epithelium which is innervated by the 4th to 6th thoracic sympathetic nerves. However, little is known about the contribution of the interactions between sympathetic nerves and breast cancer cells to the malignant progression of TNBC. Methods: The expression levels of the β2 -adrenergic receptor (β2 -AR, encoded by ADRB2 gene), nerve growth factor (NGF), and tropomyosin receptor kinase A (TrkA) were determined using immunohistochemistry (IHC). NGF expression levels in the serum were compared by enzyme-linked immunosorbent assay (ELISA). Cell proliferation was assessed using the Cell Counting Kit-8 assay. The β2 -AR, NGF, p-ERK, and p-CERB expression levels were determined using western blotting. TNBC cells and neuronal cells of the dorsal root ganglion (DRG) in 2-day-old Sprague Dawley rats were co-cultured. Using norepinephrine (NE), NGF, and β2 -AR, NGF/TrkA blocker pretreatments, the axon growth of each group of DRG neuron cells was detected by immunofluorescence analysis. Results: The sympathetic adrenergic neurotransmitter NE activated the ERK signaling pathway in TNBC cells. NE/β2 -AR signaling promotes NGF secretion. NGF further facilitates the malignant progression of TNBC by increasing sympathetic neurogenesis. In the coculture assay, the sympathetic adrenergic NE/β2 -AR signal pathway also enhanced NGF secretion. NGF binds TrkA in DRG neurons and promotes axonal growth. Conclusion These results suggest that NE/β2 -AR pathway promotes cell proliferation and NGF production in triple-negative breast cancer.

Objective To explore the potential impact pathways of self-management behavior based on COM-B model,in maintenance hemodialysis(MHD)patients,and provide reference for the intervention of self-manage-ment behavior.Methods Judgment sampling was used to select 350 MHD patients undergoing dialysis at the hospital in a certain district of Guangzhou,and a questionnaire survey was conducted among them.Smart PLS software was used to construct a partial least squares structural equation model and perform path analysis.Results Self-manage-ment behavior score of MHD patients was(57.06±13.28).Univariate analysis showed that age,education back-ground,employment status,occupational classification,per capita monthly income of families,and the number of comorbidities could directly affect self-management behavior of MHD patients(P<0.05).PLS-SEM model showed that self-efficacy(β = 0.246),family care level(β = 0.124)and social support(β = 0.140)positively impacted patients' self-management behavior,while disease perception negatively affected self-management behavior(β =-0.097).Self-efficacy can mediate the impact of disease perception and social support on self-management behavior of MHD patients(P<0.05).Conclusions Self-management behavior of MHD patients is currently at a low level.Therefore,when devising intervention plans for these patients,it is crucial to consider the combined effects of disease knowledge education,disease perception reconstruction,opportunity provision,and motivation.The primary focus should be on enhancing patients' self-efficacy,which will ultimately elevate their overall level of self-management.

Hepatic ischemia/reperfusion injury (HIRI) is a serious complication that occurs following shock and/or liver surgery. Gut microbiota and their metabolites are key upstream modulators of development of liver injury. Herein, we investigated the potential contribution of gut microbes to HIRI. Ischemia/reperfusion surgery was performed to establish a murine model of HIRI. 16S rRNA gene sequencing and metabolomics were used for microbial analysis. Transcriptomics and proteomics analysis were employed to study the host cell responses. Our results establish HIRI was significantly increased when surgery occurred in the evening (ZT12, 20:00) when compared with the morning (ZT0, 08:00); however, antibiotic pretreatment reduced this diurnal variation. The abundance of a microbial metabolite 3,4-dihydroxyphenylpropionic acid was significantly higher in ZT0 when compared with ZT12 in the gut and this compound significantly protected mice against HIRI. Furthermore, 3,4-dihydroxyphenylpropionic acid suppressed the macrophage pro-inflammatory response in vivo and in vitro. This metabolite inhibits histone deacetylase activity by reducing its phosphorylation. Histone deacetylase inhibition suppressed macrophage pro-inflammatory activation and diminished the diurnal variation of HIRI. Our findings revealed a novel protective microbial metabolite against HIRI in mice. The potential underlying mechanism was at least in part, via 3,4-dihydroxyphenylpropionic acid-dependent immune regulation and histone deacetylase (HDAC) inhibition in macrophages.

Objective To improve laboratory research of generic drugs in Chinese pharmaceutical enterprises, avoid the defects in the research process, and explore the feasibility of six sigma management (DMAIC) as improvement model in the process of generic drugs laboratory research. Methods The effectiveness of DMAIC implementation was evaluated through the literature search and case study of a generic API’s process with the DMAIC model. Results The DMAIC model was successfully applied in this case. The model made laboratory research more reasonable, helped R&D personnel to pinpoint key quality attributes and process parameters, etc., ensured the authenticity and completeness of experimental data, and provided valuable data for subsequent industrial production as well as meeting registration requirements. Conclusion DMAIC model can solve the problems, such as poor overall arrangement, poor connection with production, and irregular management. It embodied the idea of Quality by Design (QbD) and can be used as good reference for domestic laboratory research of generic drugs.

Objective To investigate the effectiveness of ultrasound in evaluating the degree of xerostomia in the patients with nasopharyngeal carcinoma ( NPC) receiving intensity?modulated radiotherapy (IMRT). Methods A total of 30 NPC patients who were admitted to our hospital from May 2013 to December 2014 were enrolled in this study. The degree of xerostomia in these NPC patients was scored according to the Radiation Therapy Oncology Group scoring criteria. Color Doppler ultrasound was used to measure the peak systolic blood flow velocity of the parotid gland and submandibular gland and the changes in vascular diameter of the parotid gland in the NPC patients before, during, and after IMRT. The correlation between each parameter and the degree of xerostomia was determined by analysis of variance. Results In the 28 NPC patients included in the statistical analysis, the degree of xerostomia during IMRT was significantly higher than that before IMRT ( P=0024 ) , and the degree of xerostomia at 3 months after IMRT was significantly lower than that during IMRT ( P=0035) . The peak systolic blood flow velocity of the parotid gland and submandibular gland and the proportion of patients with decreases in vascular diameter of the parotid gland during IMRT were significantly higher than those before IMRT ( P=0001 and 0003;P=0001);the above parameters at 3 months after IMRT were significantly lower than those during IMRT ( P=0008 and 0012;P=0001) . During IMRT and after IMRT, the degree of xerostomia was significantly correlated with the peak systolic blood flow velocity of the parotid gland ( r=0563, P=0026;r=0409, P=0031) . Conclusions Ultrasound can be used as a noninvasive detection for the hemodynamic changes in the parotid gland, and it has a certain clinical reference value for evaluating the degree of xerostomia in NPC patients during and after IMRT.

OBJECTIVE:To systematically review the efficacy of Duhuo jisheng decoction combined with chemical medicines in the treatment of ankylosing spondylitis (AS),and to provide reference for clinical treatment. METHODS:Retrieved from CBM,CJFD,VIP,Wanfang Database,PubMed and EMBase,randomized controlled trials(RCT)about Duhuo jisheng decoction combined with chemical medicines(test group)versus chemical medicines alone(control group)in the treatment of AS were col-lected,Meta-analysis was performed by using Rev Man 5.3 software after data extraction and quality evaluation. RESULTS:Total-ly 6 RCTs were included,involving 382 patients. Results of Meta-analysis showed,the total effective rate [RR=1.35,95%CI(1.20, 1.52),P<0.001],improvement rate of TCM symptoms [RR=1.31,95%CI(1.09,1.57),P=0.004)in test group were significantly higher than control group,and CRP level was lower than contxol group[MD=-6.18,95%CI(-8.49,-3.87),P<0.001],the dif-ference was statistically significant. CONCLUSIONS:Duhuo jisheng decoction combined with chemical medicines shows better effi-cacy than chemical medicines alone,it can improve the TCM symptoms and decrease the CRP level.

Objective To determine the effect of Nuclear factor-erythroid 2-related factor 2 ( Nrf2 ) on acute hephrotoxicity induced by CCl4 in male rat.Methods 20 male Wistar rats were randomly divided into control group and CCl4 group, 10 rats in each group, another 10 male Wistar rats were transgenic rats microinjection through the carrier, obtained the Nrf2-tk gene integration and specific transgenic rats, as the CCl4 +Nrf2 integration group.The groups was given 1%polysorbate 80 for 4 days,Then the CCl4 and CCl4 +Nrf2 integration group were intraperitoneally injected with a single dose of CCl47.5 mg· kg-1 and were killed 24 h after CCl4 injection.The serum chemical parameters including asparate aminotransferase ( AST) ,alanine aminotransferase ( ALT) and lactate dehydrogenase ( LDH) were measured.Also malonaldehyde ( MDA) ,glutathione ( GSH) ,oxidized glutathione ( GSSG) levels in the liver as well as glutathione ( GSH)/oxidized glutathione ( GSSG ) ratios were detected. Histopathologic changes in the liver were examined. Results F1generation TK transgenic rats in liver and testis and other tissues and organs were not detected the transcription of Nrf2-tk, indicating that Nrf2-tk expression in tissues is specific good.Nrf2 significantly reduced serum AST, ALT and LDH levels in a dose-dependent manner.The results of MDA levels and GSH/GSSG ratios in liver and kidney showed that Nrf2 reduced CCl4-induced hepatic lipid peroxidation,and ameliorated glutathione depletion.The histopathologic results showed that Nrf2 restrained liver and kidney damage induced by CCl4 .Conclusion Nrf2 can effectively protect male rat from acute hepatotoxicity and nephrotoxicity induced by CCl4 .

OBJECTIVETo investigate the curative effect of penile elongation with four differentoperative approaches.

METHODSThrough four different operative approaches (the coronary sulcus ringincision, Y or Z shaped incision or Z shaped incision combined with coronary sulcus ring incision), thepenile skin and fascia were degloved until the penile root. Then the superficial and deep dorsal penilesuspensory ligament were cut off. After electric coagulation of the residue ends, the two-side tissue at thefront of the pubic symphysis was sutured. Then the penile skin and fascia were repositioned and the incisionat the inner and outer plate was closed.

RESULTSThe increased penile static length was (2.9 ± 0.2) cmwith abdominal wall Y incision (12 cases); (3.1 ± 0.3) cm with transabdominal modified Z incision (260 cases); (3.9 ± 0.7) cm with coronary sulcus ring incision (363 cases); (3.4 ± 0.8) cm with combined incision (39 cases). The lengthening effect was significantly different between the coronary ring incision and abdominal wall Y/Z incision (P < 0.05). The postoperative follow-up period was 6 months to 5.5 years without serious complications. Only 3 cases of subcutaneous hematoma occurred with treatment of debridement and drainage. 4 cases with ischemic necrosis at distal penile skin, were treated with debridement, dressing and physiotherapy, leaving no scar.

CONCLUSIONSPenile lengthening surgery are safe and effective through different approaches. The coronal ring incision has the best therapeutic effect.

Bandages ; Debridement ; Drainage ; Electrocoagulation ; Fasciotomy ; Follow-Up Studies ; Humans ; Ligaments ; surgery ; Male ; Necrosis ; surgery ; Organ Size ; Penis ; anatomy & histology ; pathology ; surgery ; Postoperative Period ; Reconstructive Surgical Procedures ; methods ; Skin ; Time Factors

Objective The renin-angiotensin system ( RAS) is involved in myocardial anoxic injury .This study aimed to in-vestigate the expressions of AT 1-R, AT2-R, and angiotensin-converting enzyme ( ACE ) in bone marrow mesenchymal stem cells (MSCs) under hypoxia. Methods Rat MSCs were isolated, cultured, and identified with CD29 and CD11b/c antibodies.The is-chemic injury model was established by exposing the MSCs to hypoxia and serum deprivation ( Hypoxia/SD) for 24 hours, while the control cells were cultured in L-DMEM with 10%FBS.The vitality and apoptosis of the cells were detected by trypan blue staining , CCK8 assay, and Annexin V-FITC staining.The mRNA and protein expressions of AT 1-R, AT2-R, and ACE were determined by real-time quantitative PCR and Western blot , respectively. Results The positive rate of CD29 was >97%and that of CD11b/c was <1% in the MSCs.Compared with the control group, Hypoxia/SD significantly increased the rate of cell apoptosis ([6.73 ±0.78]%vs [19.93 ±4.92]%, P<0.01), decreased the rate of cell viability ([78.49 ±4.94]%vs [37.33 ±2.91]%, P<0.01), and up-regulated the mRNA and protein expressions of AT 1-R, AT2-R, and ACE. Conclusion Hypoxia/SD activates the RAS in MSCs and improves the protective function of the cells against myocardial anoxic injury .