Aim To investigate whether notoginsenoside Rl (PNS-R1) alleviates allergic rhinitis (AR) through AMP-activated protein kinase (AMPK)/mitochondrial fission critical protein (DRP1) -mediated mitochondrial fission. Methods Different doses of PNSRl were used to treat ovalbumin (OVA) -induced AR model mice,and the inhibitory effect of PNS-R1 on AR was investigated by observing allergic symptoms such as nasal rubbing and sneezing, as well as HE staining of nasal tissues. Serum IgE levels and nasal lavage fluid (NLF) inflammatory cytokine levels were detected by enzyme-linked immunosorbent assay (ELISA) and apoptosis-related proteins were detected by Western blot. In vitro human nasal epithelial cells (HNEpC) were stimulated with IL-13 to observe apoptosis, mitochondrial membrane potential, cellular ROS and mitochondrial ROS production, as well as the expression levels of AMPK/DRP1, expression levels of the TXNIP/NLRP3 inflammasomes and the translocation of DRP1. Results PNS-R1 attenuated allergic symptoms in AR mice, HE staining reduced inflammatory cells and reduced the levels of OVA-specific IgE in serum, and the levels of IL-4, IL-6, and IL-8 in NLF. PNS-R1 attenuated the apoptosis and ROS production of nasal epithelial cells in AR. In vitro PNS-R1 could up-regulate mitochondrial membrane potential after IL-13 stimulation, reduce ROS and mtROS production, the proportion of apoptotic positive cells, and reduce cleaved caspase-3, Bax, and up-regulate Bcl-2 expression, down-regulate DRP1 phosphorylation (Ser 616) and DRP1 translocation at the mitochondrial membrane in an AMPK-dependent manner, reducing TXNIP/NLRP3 expression. Conclusions PNS-R1 can protect mitochondrial integrity by inhibiting the AMPK/DRP1 signaling axis and its subsequent TXNIP/NLRP3 signaling axis,thereby alleviating rhinitis in AR mice.

Objective: To establish reference values for carotid intima-media thickness (CIMT) of adult dwellers in Shenzhen City. Methods: The study was conducted based on the Shenzhen heart failure epidemiological survey from 2021 to 2022. In this survey, residents aged 18 years and above in Shenzhen were selected by using a multi-stage stratified random sampling method. General information, cardiovascular disease (CVD) related behavior and carotid ultrasound examination and etc. were collected from the participants. People with CVD factors, a history of atherosclerotic cardiovascular disease, carotid plaque or having no carotid ultrasound examination results were excluded. The parameter regression model based on fractional polynomial was used to establish the reference values of CIMT by age and sex. Results: A total of 2 163 healthy individuals were enrolled in the final analysis, including 576 males (26.6%) and 1 587 females (73.4%). The fractional polynomial regression of the CIMT mean and standard deviation was obtained. For men, the regression was mean_CIMT=0.324 7+0.006 9×age and SD_CIMT=0.076 9+0.001 2×age. For women, the regression was mean_CIMT=0.354 9+0.005 4×age and SD_CIMT=0.041 6+0.002 0×age. Conclusion: The age and sex reference values for CIMT of adult people in Shenzhen established in this study could provide the latest reference standards for early screening of subclinical CVD.
Male ; Humans ; Adult ; Female ; Carotid Intima-Media Thickness ; Cardiovascular Diseases ; Reference Values ; Carotid Arteries/diagnostic imaging* ; Ultrasonography, Carotid Arteries ; Risk Factors ; Carotid Artery Diseases

OBJECTIVE: To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes in patients with multiple myeloma (MM). METHODS: Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RT-qPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve. RESULTS: The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group (P<0.001), while the expression level of miR-146a between the two groups was not significantly different (P>0.05). The expression level of miR-21 was strongly negatively correlated with serum β₂-microglobulin concentration (r=-0.830), and weakly negatively correlated with serum creatinine, corrected serum calcium, and cystatin C (r=-0.488, -0.282, -0.627). The expression levels of Let-7b and miR-18a were also weakly negatively correlated with the corrected serum calcium, β₂-microglobulin, and cystatin C concentration (r=-0.305, -0.362, -0.461; -0.317, -0.542, -0.434). However, there was no significant correlation between the expression level of miR-146a and routine laboratory parameters in MM patients. The overall survival rate of MM patients with low expression level of miR-21, miR-18a, and Let-7b significantly decreased compared with high expression level group (P<0.05), however, the expression level of miR-146a was not related to the overall survival rate. CONCLUSION Aberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM, which are associated with a worse overall survival rate.
Calcium/metabolism* ; Creatinine/metabolism* ; Cystatin C/metabolism* ; Exosomes/metabolism* ; Humans ; MicroRNAs/metabolism* ; Multiple Myeloma/metabolism*

As the body ages， the immune system will undergo a series of changes， which are termed "immunosenescence" and are embodied in immune cells. Previous studies have shown that the immune cells involved in the regulation of immunosenescence include intrinsic immune cells and adaptive immune cells. Intrinsic immune cells are neutrophils， monocytes/macrophages， myeloid-derived suppressor cells， dendritic cells， natural killer cells， etc.， and the underlying mechanisms involve the regulation of cell number， phagocytosis， chemotaxis， adhesion， the function of toll-like receptor （TLR）， antigen presentation， macrophage polarization， cytotoxicity， migration， etc. The adaptive immune cells include T-lymphocytes and B-lymphocytes， and the underlying mechanisms involve the regulation of cell development， proliferation， differentiation， cell number， telomerase activity， self-reactive antibodies， etc. Immunosenescence is the manifestation of aging in the human body and is also an important target for delaying aging by Chinese medicine and western medicine. In recent years， scholars have found some classical prescriptions and their active components （such as Dushentang and total saponins in Panax ginseng leaves， and Shengmaiyin and anwulignan and total saponins in P. ginseng stems and leaves） can regulate immunosenescence by targeting the immune cells and interfering with their molecular regulatory mechanisms. In addition， the mechanisms of the classical prescriptions in regulating immunosenescence are closely related to autophagy. The representative prescription embodying the therapeutic principles of resolving blood stasis and promoting regeneration， Dahuang Zhechongwan， can delay D-galactose-induced renal aging in mice， and its underlying mechanisms are related to the regulation of the number and activity of thymic immune cells and improvement of the protein expression of autophagy-related markers and inflammatory cytokines in the kidney. Therefore， exploring the effects of the classical prescriptions and their active components by targeting the mechanisms of immunosenescence will become a new direction for investigating and developing anti-aging drugs.

Objective: To compare the effects of 3 treatment strategies (emergent surgery, self-expanding metallic stents, self-expanding metallic stents plus neoadjuvant chemotherapy) on postoperative anal function and quality of life in patients with complete obstructive left hemicolon cancer. Methods: A retrospective cohort study was conducted. Clinical data of patients with complete obstructive left hemicolon cancer admitted to General Surgery Department of Beijing Chaoyang Hospital between January 2017 and October 2019 were retrospectively collected. Patient inclusion criteria: (1) complete obstructive left hemicolon cancer was confirmed through clinical manifestation and abdominal computed tomography; (2) adenocarcinoma was confirmed by postoperative pathology; (3) emergent radical resection of primary tumor was performed with temporary stoma, or radical resection of primary tumor and primary anastomosis was performed without stoma, 7 to 14 days after completion of insertion of self-expanding metallic stents. Patients who did not receive stoma reversion after emergent operation were excluded. According to different therapies, patients were divided into three groups: emergent surgery (ES) group, self-expanding metallic stents (SEMS) group and self-expanding metallic stents plus neoadjuvant chemotherapy (SEMS+NAC) group. Wexner score for incotinence (higher score indicates the worse anal function), Vaizey score (>10 indicates fecal incontinence) and low anterior resection syndrome (LARS) scale (higher score indicates the worse anal function) were applied to evaluate anal function of patients among groups at postoperative 1-, 6- and 12-month. EORTC QLQ-C30 questionnaire was used to assess the quality of life. Risk factors of decreased anal function were identified by logistic regression analysis. Results: A total of 72 patients were enrolled, including 27 (37.5%) patients in ES group, 23 (31.9%) in SEMS group and 22 (30.6%) in SEME+NAC group. The baseline characteristics including age, gender, tumor location, comorbidities, total blood loss, operation time and postoperative complications, were comparable among groups, except that the proportion of laparoscopic surgery was significantly lower in ES group (4/27, 14.9%) than that in SEMS (15/23, 65.2%) and SEMS+NAC group (16/22, 72.7%) with significant difference (P<0.001). The follow-up ended up to October 2020, and the overall follow-up rate was 79.2% (57/72). No significant differences existed in the Wexner score of patients among groups at postoperative 1-, 6- and 12-month (all P>0.05). The Vaizey scores at postoperative 1-month in ES, SEMS and SEMS+NAC group were 7 (0-17), 3 (0-7) and 4 (0-8) respectively with significant difference (H=18.415, P=0.001), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). Vaizey scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The LARS scores at postoperative 1-month in ES, SEMS and SEMS+NAC groups were 20 (0-37), 15 (0-24) and 16 (0-28) respectively with significant difference (H=3.660, P=0.036), and the scores in SEMS and SEMS+NAC groups were significantly lower than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC groups (P>0.05). LARS scores at postoperative 6- and 12-month among 3 groups were not significantly different (both P>0.05). The QLQ-C30 score revealed that the social function of patients in SEMS group and SEMS+NAC group was significantly better than that in ES group (both P<0.05), while no significant difference existed between SEMS and SEMS+NAC group (P>0.05). The logistic regression analysis revealed that only ES was an independent risk factor of decreased anal function (OR=2.264, 95% CI: 1.098-4.667, P=0.027). Conclusion: Compared to ES, SEMS may improve quality of life and short-term anal function of patients with complete obstructive left hemicolon cancer.
Humans ; Intestinal Obstruction ; Postoperative Complications ; Quality of Life ; Rectal Neoplasms ; Retrospective Studies ; Syndrome ; Treatment Outcome

Adult ; Brain ; diagnostic imaging ; physiopathology ; Diffusion Tensor Imaging ; Female ; Hallucinations ; diagnostic imaging ; physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; White Matter ; diagnostic imaging ; physiopathology ; Young Adult

Objective To investigate the sequential changes of the number of neutrophils and myofibroblasts during diabetic wound healing, and discuss its application value in wound age estimation. Methods Diabetic DB mice and mice of the same age in the normal control group were selected, a wound healing model was established, wound samples were taken at different time points, while the number of neutrophils and myofibroblasts during diabetic wound healing were determined by immunohistochemical staining technique. Results The number of infiltrated neutrophils in the wounds of control and diabetic groups reached the peak respectively at 12 h and 5 d after injury. Compared with the control group, the number of neutrophils in the diabetic group decreased significantly from 6 h to 1 d after injury, but increased markedly from 5 d to 14 d. From 5 d to 10 d after injury, the average number of neutrophils at high magnification in wounds of the diabetic group was over 30, while that of neutrophils in wounds of the control group was less than 20. Myofibroblasts appeared in wounds from 3 d to 14 d after injury in the control group and from 5 d to 14 d after injury in the diabetic group. The difference in the number of myofibroblasts in wounds between control group and diabetic group from 3 to 7 d after injury had statistical significance. Conclusion In comparison with normal wound healing, the number of neutrophils and myofibroblasts during diabetic wound healing shows different sequential changes. The results of this study can provide reference for wound age estimation of patients with severe diabetes.
Animals ; Diabetes Mellitus, Experimental/pathology* ; Mice ; Myofibroblasts ; Neutrophils ; Wound Healing/physiology*

BACKGROUNDRepetitive transcranial magnetic stimulation (rTMS) and event-related potentials (ERPs) are a noninvasive technique that widely used in neurophysiological field. Although rTMS has shown clinical utility for a number of neurological conditions, Recently,there was little understanding of the the efficacy of rTMS on Schizophrenia(SZ) and the change of ERP between before and after rTMS treatment. The objective of this study was to investigate the characteristics of N400, mismatch negativity (MMN), and P300 before and after treatment with rTMS in SZ.

METHODSOne hundred and twenty-seven SZ patients hospitalized in Shanghai Mental Health Center from March 2015 to July 2017, divided into two groups (85 patients were recruited as rTMS group and 42 were recruited as sham rTMS [ShrTMS] group) and 76 normal controls (NCs) who were the staff and refresher staff in our hospital were recruited at the same time. A Chinese-made rTMS and a Runjie WJ-1 ERPs instrument were used in the present experiment. N400 was elicited by congruent and noncongruent Chinese idioms. After rTMS treatment, N400, P300, and MMN characteristics were compared with those before treatment and NC group.

RESULTSCompared with NC, the SZ patients exhibited delays in N400, P300, and MMN latency and decreased N400, P300, and MMN amplitudes in their frontal area (P < 0.05). After 25 rTMS treatments, N400 amplitudes in the frontal area (elicited by idioms with same phonic and different shape and meaning and with different phonic, shape, and meaning) were increased in the SZ patients (P < 0.05). However, there was no significant change in N400 before and after treatment with ShrTMS in SZ patients (P > 0.05). Amplitudes for MMN and target P300 also increased in SZ patients after rTMS treatment (P < 0.05).

CONCLUSIONSBased on our preliminary findings, we believe that the combined usage of N400, MMN, and P300 could be a valuable index and an electrophysiological reference in evaluating the effects of rTMS treatment in SZ patients.

BackgroundRisperidone and paliperidone have been the mainstay treatment for schizophrenia and their potential role in neuroprotection could be associated with brain-derived neurotrophic factor (BDNF) and N400 (an event-related brain potential component). So far, different effects on both BDNF and N400 were reported in relation to various antipsychotic treatments. However, few studies have been conducted on the mechanism of risperidone and paliperidone on BDNF and N400. This study aimed to compare the effects of risperidone and paliperidone on BDNF and the N400 component of the event-related brain potential in patients with first-episode schizophrenia.

MethodsNinety-eight patients with first-episode schizophrenia were randomly divided into the risperidone and paliperidone groups and treated with risperidone and paliperidone, respectively, for 12 weeks. Serum BDNF level, the latency, and amplitude of the N400 event-related potential before and after the treatment and Positive and Negative Syndrome Scale (PANSS) scores were compared between the two groups.

ResultsA total of 94 patients were included in the final analysis (47 patients in each group). After the treatment, the serum BDNF levels in both groups increased (all P < 0.01), while no significant difference in serum BDNF level was found between the groups before and after the treatment (all P > 0.05). After the treatment, N400 amplitudes were increased (from 4.73 ± 2.86 μv and 4.51 ± 4.63 μv to 5.35 ± 4.18 μv and 5.52 ± 3.08 μv, respectively) under congruent condition in both risperidone and paliperidone groups (all P < 0.01). Under incongruent conditions, the N400 latencies were shortened in the paliperidone group (from 424.13 ± 110.42 ms to 4.7.41 ± 154.59 ms, P < 0.05), and the N400 amplitudes were increased in the risperidone group (from 5.80 ± 3.50 μv to 7.17 ± 5.51 μv, P < 0.01). After treatment, the total PANSS score in both groups decreased significantly (all P < 0.01), but the difference between the groups was not significant (P > 0.05). A negative correlation between the reduction rate of the PANSS score and the increase in serum BDNF level after the treatment was found in the paliperidone group but not in the risperidone group.

ConclusionsBoth risperidone and paliperidone could increase the serum BDNF levels in patients with first-episode schizophrenia and improve their cognitive function (N400 latency and amplitude), but their antipsychotic mechanisms might differ.

Antipsychotic Agents ; pharmacology ; Brain-Derived Neurotrophic Factor ; drug effects ; China ; Electroencephalography ; Evoked Potentials ; drug effects ; Female ; Humans ; Male ; Paliperidone Palmitate ; pharmacology ; Risperidone ; pharmacology ; Schizophrenia ; drug therapy

OBJECTIVETo evaluate biological effects of OCT4A gene on K562 cells and explore the molecular mechanism of K562 cell apoptosis.

METHODSTwo recombinant lentiviral vectors were constructed, which could stablely up- regulate and down- regulate OCT4A protein. Recombinant lentivirus was generated by co-transfection of three-plasmids and transfec-ted into K562 cells. The experiments were divided into 5 groups: normal, pLVX-OCT4A-ZsGreen1, pLVX vector control, PLB-OCT4A shRNA and non-specific shRNA groups. Western blot was applied to detect the expression of OCT4A protein, the cell counting kit-8 was applied to evaluate the effect of OCT4A on proliferation of K562 cells. The apoptosis and differentiation of K562 cells were detected by flow cytometry with AnnexinV/7-AAD double staining. The mRNA expressions of caspase-3,BIM,BCL-xL,BAX in K562 cells were determined by real time PCR.

RESULTSThe OCT4A fragment was amplified by reverse transcription polymerase chain reaction(RT-PCR), the 2 lentiviral vectors were successfully constructed. In comparson with those in the control group, the expression of OCT4A protein of pLVX-OCT4A-ZsGreen1 group was significantly increased, but decreased in PLB-OCT4A shRNA group. CCK-8 assay showed that the higher the content of OCT4A protein, the faster the cell proliferation. The apoptosis rate was (3.48±0.52)% of pLVX-OCT4A-ZsGreen1 group, which was lower than that of control group, while the apoptosis rate PLB-OCT4A shRNA group was (7.25±0.57)%, which was higher than that of control group (P<0.05), however, the K562 cells differentiation was not influenced(P>0.05). Compared with control group, the gene expression of Caspase-3,BIM and BAX was down-regulated(P>0.05), but a significant up-regulation of BCL-xL gene expression was observed(P<0.05).

CONCLUSIONTwo lentiviral vectors have been successfully constructed, which can stably up- and down- regulate the expression of OCT4A in K562 cells respectively. OCT4A can promote the K562 cell proliferation and inhibit the apoptosis, the mechanism may be related with up-regulation of BCL-xl expression.

Apoptosis ; Cell Proliferation ; Genetic Vectors ; Humans ; K562 Cells ; Lentivirus ; Octamer Transcription Factor-3 ; genetics ; Transfection