BACKGROUND:Stand-alone oblique lateral interbody fusion has a high rate of complications of fusion segment sink.Oblique lateral interbody fusion with posterior fixation can provide stable support,but intraoperative position changes and double incisions weaken the advantages of this technique.Oblique lateral interbody fusion combined with lateral plate fixation can achieve one-stage decompression in the same incision,while the lateral internal fixation provides stable support. OBJECTIVE:To analyze the short-term efficacy of oblique lateral interbody fusion combined with lateral plate fixation in the treatment of single-level lumbar degenerative disease. METHODS:The clinical data of 34 patients with single-level lumbar degenerative disease treated with oblique lateral interbody fusion combined with lateral plate fixation were collected from May 2020 to October 2022.Among them,14 were males and 20 were females aged from 41 to 72 years at the mean age of(58.6±9.9)years.There were 11 cases of lumbar spondylolisthesis(Ⅰ°),7 cases of lumbar disc herniation with segmental instability,and 16 cases of lumbar spinal stenosis.Operation time,blood loss,and complications were recorded.Visual analog scale scores of lumbago,radiative pain of both lower limbs,and Oswestry disability index scores were evaluated before surgery,3 months after surgery,and the last follow-up.Dural sac cross-sectional area,intervertebral height,and intervertebral fusion were measured and observed. RESULTS AND CONCLUSION:(1)The 34 patients were followed up for 14-36 months,with an average of(21.3±5.2)months.(2)The operation time ranged from 50 to 92 minutes,with an average of(68.5±11.1)minutes.Intraoperative blood loss was 50-170 mL,with an average of(71.6±25.3)mL.(3)Compared with the preoperative results,the visual analog scale scores and Oswestry disability index scores were significantly decreased at 3 months after surgery and at the last follow-up(P<0.001),and the maximum Oswestry disability index scores were improved by nearly 50％.(4)Bone fusion was achieved in all patients during half-year follow-up.The overall complication rate was 21％(7/34),including 1 case of plate displacement,3 cases of cage subsidence,1 case of psoas weakness,and 2 cases of anterior thigh pain.(5)It is concluded that oblique lateral interbody fusion combined with lateral plate fixation for the treatment of lumbar degenerative diseases has the characteristics of less blood loss,short operation time,rapid postoperative recovery,and significant short-term clinical efficacy with the stable support to a certain extent.The long-term curative effect needs further follow-up observation.

Chronic visceral pain is a persistent and debilitating condition arising from dysfunction or sensitization of the visceral organs and their associated nervous pathways. Increasing evidence suggests that imbalances in central nervous system function play an essential role in the progression of visceral pain, but the exact mechanisms underlying the neural circuitry and molecular targets remain largely unexplored. In the present study, the ventral tegmental area (VTA) was shown to mediate visceral pain in mice. Visceral pain stimulation increased c-Fos expression and Ca²⁺ activity of glutamatergic VTA neurons, and optogenetic modulation of glutamatergic VTA neurons altered visceral pain. In particular, the upregulation of NMDA receptor 2A (NR2A) subunits within the VTA resulted in visceral pain in mice. Administration of a selective NR2A inhibitor decreased the number of visceral pain-induced c-Fos positive neurons and attenuated visceral pain. Pharmacology combined with chemogenetics further demonstrated that glutamatergic VTA neurons regulated visceral pain behaviors based on NR2A. In summary, our findings demonstrated that the upregulation of NR2A in glutamatergic VTA neurons plays a critical role in visceral pain. These insights provide a foundation for further comprehension of the neural circuits and molecular targets involved in chronic visceral pain and may pave the way for targeted therapies in chronic visceral pain.
Animals ; Male ; Visceral Pain/metabolism* ; Up-Regulation/physiology* ; Ventral Tegmental Area/metabolism* ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors* ; Neurons/drug effects* ; Mice, Inbred C57BL ; Mice ; Proto-Oncogene Proteins c-fos/metabolism* ; Chronic Pain/metabolism* ; Glutamic Acid/metabolism*

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

Research on the participation of exosomes in pathogenesis and prognosis of multiple myeloma(MM)has made encouraging progress.However,the specific mechanism has not yet been clarified.Recently,domestic and foreign researchers have pressed forward on deeper study on exosomes.This article mainly summarizes the role of exosomes in the pathophysiological processes,such as bone marrow microenvironment changes,immunosuppression,myeloma bone disease generation and myeloma drug resistance,so as to provide new reference for further clinical research of exosomes as potential biomarkers for MM.

Objective To explore the association between R611H(G/A,rs734312)variation of WFS1 gene and early-onset type 2 diabetes mellitus(T2DM).Methods A total of 181 Chinese patients with early-onset T2DM(T2DM group)and 196 non-diabetic controls(NC group)were enrolled in this study.The rs734312 variation was detected by PCR-direct sequencing.Genotypic and allelic frequencies of rs734312 and clinical variables were compared and analyzed between the two groups.Results Compared with the NC group,the frequencies of AA genotype and A allele in R611H(G→A)variation were significantly elevated in the early-onset T2DM group,AA vs GA+GG(OR 1.720,95%CI 1.100～2.680,P<0.05).A vs G(OR 1.500,95%CI 1.020～2.220,P<0.05).The remarkable differences of frequencies of genotype and allele in rs734312(G/A)were observed between Asians(China,Japan and Korea)and Caucasians(Denmark,Britain,Spain,France and Russia,P<0.01 for each).Compared with AA genotype,fasting and 2 hours postprandial insulin(FIns and 2 hIns)as well as HOMA-β were significantly rise in GG+GA genotype carriers of early-onset T2DM group(P<0.05).Conclusions The a allele of rs734312 in WFS1 may be a risk factor for early-onset T2DM in Chinese population,and the variation might be a potential genetic marker for predicting the islet β-cell dysfunction in early-onset T2DM in Chinese population.

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

ObjectiveTo establish a UHPLC-MS/MS quantitative method for the determination of glucuronic acid， tartaric acid， glycolic acid， malic acid， lactic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid in cosmetics. MethodsSamples were prepared by ultrasonic extraction， cleansed by precipitating reagent and followed by high-speed centrifugation of the extraction solution. The supernatant was filtered by 0.22 μm Millipore filter. The continued filtrate was taken for analysis. A reversed phase column， Poroshell 120 EC-C₁₈ （2.7 μm， 4.6 mm×1 000 mm） was used with 0.1% formic acid buffer and acetonitrile as the mobile phase under the condition of gradient elution. The analytes were detected with electrospray ionization source in negative ion mode （ESI^-） and multiple reactions monitoring （MRM）， and quantified by external standard curve. ResultsThe method showed a good linearity of glucuronic acid， tartaric acid， malic acid， DL-2-hydroxybutyric acid sodium， benzilic acid， hydroxycaprylic acid and N-acetylneuraminic acid within the concentration range of 50.0‒2 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of glycolic acid， lactic acid， citric acid and mandelic acid within the concentration range of 100.0‒5 000.0 μg·L^-1 （r>0.995）. The method showed a good linearity of lactobionic acid and gluconic acid within the concentration range of 50.0‒5 000.0 μg·L^-1 （r>0.995）. The recoveries were in the range of 92.3%‒114.1%； the relative standard deviations （RSD） were in the range of 0.9%‒6.0% （n=3）. The detection limits of glucuronic acid， tartaric acid， malic acid， citric acid， DL-2-hydroxybutyric acid sodium， mandelic acid， benzilic acid， hydroxycaprylic acid， lactobionic acid， gluconic acid and N-acetylneuraminic acid were 0.003% while the detection limits of glycolic acid， lactic acid and mandelic acid were 0.006%. In 10 batches of commercially available cosmetics， eight batches showed positive result. ConclusionThe UHPLC-MS/MS method is efficient， sensitive and accurate and is applicable to the determination of 13 α-hydroxy acidic components in cosmetics.

Objective To explore the effects of Qingshen Granules(QSG)on adenine-induced renal fibrosis in mice and in uric acid(UA)-stimulated NRK-49F cells and its mechanism for regulating exosomes,miR-330-3p and CREBBP.Methods A mouse model of adenine-induced renal fibrosis were treated daily with QSG at 8.0 g·kg-1·d-1 via gavage for 12 weeks.An adeno-associated virus vector was injected into the tail vein,and renal tissues of the mice were collected for analyzing exosomal marker proteins CD9,Hsp70,and TSG101 and expressions of Col-Ⅲ,α-SMA,FN,and E-cad using Western blotting and immunofluorescence and for observing pathological changes using HE and Masson staining.In the cell experiment,NRK-49F cells were stimulated with uric acid(400 μmol/L)followed by treatment with QSG-medicated serum from SD rats,and the changes in expressions of the exosomal markers and Col-Ⅲ,α-SMA,FN,and E-cad were analyzed.Dual luciferase reporter assay was employed to examine the targeting relationship between miR-330-3p and CREBBP,whose expressions were detected by RT-qPCR and Western blotting in treated NRK-49F cells.Results The mouse models of adenine-induced renal fibrosis showed significantly increased levels of CD9,Hsp70,and TSG101,which were decreased by treatment with QSG.The expressions of Col-Ⅲ,α-SMA,and FN increased and E-cad decreased in the mouse models but these changes were reversed by QSG treatment.QSG treatment obviously alleviated renal fibrosis in the mouse models.Intravenous injection of adeno-associated viral vector obviously inhibited miR-330-3p,increased CREBBP levels,and reduced fibrosis in the mouse models.Dual luciferase assay confirmed CREBBP as a target of miR-330-3p,which was consistent with the results of the cell experiments.Conclusion QSG inhibits renal fibrosis in mice by regulating the exosomes,reducing miR-330-3p levels,and increasing CREBBP expression.

The plateau environment is characterized by low oxygen, low air pressure, low temperature, and strong ultraviolet rays, etc. Chronic obstructive pulmonary disease (COPD) is a preventable and treatable chronic lung disease. High altitude environment increases COPD prevalence, clinical manifestation and mortality. The therapeutic window of theophylline drugs for COPD is narrow, and the high altitude environment has an influence on the pharmacokinetics of the drugs. This review summarizes the differences in the prevalence, mortality, clinical manifestation and clinical symptoms of COPD in the plateau and plain, providing a basis for identifying the risk factors of COPD in the plateau areas. The effects of plateau hypoxic environment on the pharmacokinetics of COPD drugs were also discussed. It can provide a rationale for more effective prevention and treatment of COPD at high altitude.
Humans ; Altitude ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Oxygen ; Hypoxia

This study aimed to evaluate the cost-effectiveness of Chaiyin Granules compared with Oseltamivir Phosphate Capsules in the treatment of influenza(exogenous wind-heat syndrome). Based on a randomized, double-blind, positive drug parallel control clinical trial, this study evaluated the pharmacoeconomics of Chaiyin Granules with cost-effectiveness analysis method. A total of 116 patients with influenza from eight hospitals(grade Ⅱ level A above) in 6 cities were selected in this study, including 78 cases in the experimental group with Chaiyin Granules and Oseltamivir Phosphate Capsules placebo, and 38 cases in the control group with Oseltamivir Phosphate Capsules and Chaiyin Granules placebo. The total cost of this study included direct medical cost, direct non-medical cost, and indirect cost. The remission time of clinical symptoms, cure time/cure rate, antipyretic onset time/complete antipyretic time, viral nucleic acid negative rate, and traditional Chinese medicine(TCM) syndrome curative effect were selected as the effect indicators for cost-effectiveness analysis. Four-quadrant diagram was used to estimate the incremental cost-effectiveness ratio. The results showed that Chaiyin Granules were not inferior to Oseltamivir Phosphate Capsules in the remission time of clinical symptoms of influenza(3.1 d vs 2.9 d, P=0.360, non-inferiority margin was 0.5 d). Compared with Oseltamivir Phosphate Capsules, Chaiyin Granules would delay the remission time of clinic symptoms of influenza for 1 d, but could save 213.9 yuan. 1 d delay in cure time could save 149.3 yuan; 1% reduction in the cure rate could save 8.2 yuan; 1 d delay in antipyretic onset time could save 295.4 yuan; 1 d delay in complete antipyretic time could save 114.3 yuan; 1% reduction in the 5-day cure rate of TCM syndrome could save 19.2 yuan. Different from other indicators, there was no statistically significant difference between two groups in the effect of negative conversion rate of viral nucleic acid, but the cost was lower and the effect was superior, and the pharmacoeconomics was not different from that of Oseltamivir Phosphate Capsules in the field of influenza treatment.
Humans ; Antipyretics/therapeutic use* ; Antiviral Agents/therapeutic use* ; Cost-Effectiveness Analysis ; Influenza, Human/drug therapy* ; Nucleic Acids/therapeutic use* ; Oseltamivir/therapeutic use* ; Phosphates/therapeutic use* ; Treatment Outcome ; Double-Blind Method