OBJECTIVE To investigate the therapeutic effect and mechanism of Qiwei dongqingye powder （QDP） on bronchial asthma in mice. METHODS The mice were divided into blank group （normal saline）， model group （normal saline）， dexamethasone group （2 mg/kg）， and QDP low-， medium-， and high-dose groups （200， 400， 800 mg/kg）， with 14 mice in each group. Except for the blank group， mice in all other groups were given ovalbumin via intraperitoneal injection followed by aerosol inhalation to induce a bronchial asthma model. During the modeling process， mice in each group were administered corresponding drug solutions or normal saline intragastrically/intraperitoneally. After the last medication， the number of cells in the bronchoalveolar lavage fluid （BALF） of the mice was observed and counted； the pathological changes of the bronchus and lung tissue were observed； the levels of malondialdehyde （MDA）， nitric oxide （NO）， total superoxide dismutase （T-SOD）， and glutathione peroxidase （GSH-Px） in the lung tissue of the mice were determined， and the level of interleukin-17 （IL-17） in the BALF and serum was determined. Transcriptomics was employed to predict and validate the mechanism of action of QDP against bronchial asthma. RESULTS Compared with the model group， the total cell count， neutrophil count， lymphocyte count， and macrophage counts in the BALF of the QDP high-dose group were all significantly reduced （ P ＜0.05）； the levels of MDA and NO in the lung tissue， and the levels of IL-17 in the BALF and serum were all decreased significantly （ P ＜0.05）； the levels of T-SOD and GSH-Px were significantly increased （ P ＜0.05）； the arrangement of lung tissue cells tended to normalize， with reduced infiltration of inflammatory cells and decreased exfoliation of bronchial simple columnar epithelial cells. The transcriptomic results revealed that the differentially expressed genes were B-cell receptor signaling pathway， nuclear factor κB （NF-κB） signaling pathway， ferroptosis signaling pathway， and others. Further validation revealed that， compared with the model group， the expression levels of NF-κB p65 and chemokine ligand 20， as well as the phosphorylation level of NF-κB inhibitor protein α， were significantly decreased in the lung tissues of the mice in all QDP groups （ P ＜0.05）. Conversely， the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and heme oxygenase 1 （HO-1） were significantly increased （ P ＜0.05）. CONCLUSIONS QDP can effectively alleviate bronchial asthma by inhibiting the NF-κB signaling pathway， activating the Nrf2/HO-1 signaling pathway， regulating oxidative stress， and reducing inflammatory responses.

A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.

Oral solid dosage forms require processes such as disintegration and dissolution to release the drug before it can be absorbed and utilized by the body. In this manuscript, imaging technology was used to continuously visualize and characterize the in vitro static drug release process of gliclazide modified release tablets from 15 manufacturers, combined with the traditional method of in vitro dissolution testing, to determine the release profile of gliclazide modified release tablets, to evaluate the similarity of the release profiles by using the similarity factor (f₂) method and based on the analysis of the release profiles fitted with a variety of mathematical models. The results indicate that the gliclazide modified release tablets produced by 14 companies are hydrophilic gel matrix tablets. Compared to the reference listed drug, the release profiles of formulations from 11 companies show high similarity (f₂ > 50) to the reference. Among these, formulations with visual characteristics similar to the reference exhibit similar release curves. This study provides an alternative method for the in vitro consistency evaluation of gliclazide modified release tablets, aiming to assess the in vitro release behaviour of generic formulations more accurately and comprehensively.

AIM:To study the relationship between ocular parameters and lens thickness(LT)in myopic patients with different anterior chamber depth(ACD).METHODS:Cross-sectional study. A total of 118 myopic subjects(236 eyes)underwent posterior chamber phakic implantable collamer lens(Phakic-ICL)implantation in the refractive department of our hospital from May 2022 to May 2024 were selected. Ocular parameters examined before surgery included uncorrected visual acuity(UCVA), subjective refraction, best corrected visual acuity(BCVA), contactless intraocular pressure(IOP), ACD, white-to-white(WTW), horizontal sulcus-to-sulcus(STSH), vertical sulcus-to-sulcus(STSV), and LT. ACD without corneal thickness was measured by Pentacam, and subjects were divided into three groups: shallow anterior chamber group(2.8 mm≤ACD≤3.2 mm), middle anterior chamber group(3.2 mm3.4 mm). The differences in WTW, STSH, STSV, and LT among groups were compared, and the correlation between the above parameters under different ACD groups was analyzed, as well as the multiple linear regression analysis was used to research LT with the above ocular parameters.RESULTS:There was no statistically significant difference in LT between the middle ACD group and the deep ACD group(P=1.00), while there were statistically significant differences in LT between shallow and middle ACD groups(P<0.0167); there were statistical significant differences in WTW, STSH and STSV among different ACD groups(F=226.36, 15.58, 11.92, all P<0.01), but the differences were varied after pairwise comparison. There was a weak negative correlation between LT and ACD only in the shallow ACD group and overall data of patients(r=-0.231, P<0.05; r=-0.222, P<0.01). There was no correlation in LT and ocular parameters between the middle ACD group and deep ACD group(all P>0.05); moderate correlations were discovered among WTW, STSH and STSV in different ACD groups and overall data(all P<0.01); in the overall data of patients, ACD had weak to low correlations with WTW, STSH, STSV and LT(all P<0.01). Through multiple linear regression analysis, it was found that only the shallow ACD group and the overall data had statistically significant independent variables that were linearly correlated with LT, and their equations were as follows: LTS=5.492-0.167×WTW+0.267×STSV-0.448×ACD; LTT=3.884-0.303×ACD, the corrected R2 of equations showed low values, revealed 0.141 and 0.056, respectively.CONCLUSION:Among different ACD groups, there was no correlation or linear relationship between LT and WTW, STSH and STSV; in the shallow ACD group and the overall data, LT had a weak negative correlation with ACD, and its corrected R2 was low. Therefore, there is no linear relationship between LT and ocular diameter parameters under different ACD.

Haloacetic acids(HAAs),as a class of disinfection byproducts in drinking water,pose potential threats to human health,so the rapid,accurate and simultaneous detection of HAAs is of great significance for ensuring drinking water safety.Aiming at the challenges in HAAs detection and risk analysis,a novel method for synchronous rapid detection of seven kinds of HAAs in drinking water based on in situ derivatization technology and headspace gas chromatography was developed in this study.Through single-factor optimization experiments,the optimal reaction parameters for in situ derivatization were determined,including the type and dosage of salting-out agent,the acidity of reaction system,the amount of phase transfer catalyst,the dosage of derivatization agent,and the extraction solvent volume.Methodologic validation showed that the seven kinds of HAAs exhibited excellent linear relationships within their respective detection concentration ranges(R2>0.998).The method detection limits(MDLs)ranged from 0.04 to 0.33 μg/L,and the limits of quantification(LOQs)were between 0.14 and 1.34 μg/L.For real water samples,the average spiked recoveries of the seven HAAs ranged from 90.9%to 107.7%,with relative standard deviation(RSDs)between 1.55%and 6.49%,and the HAAs contents in all tested samples were below the limits specified in the Standards for Drinking Water Quality(GB 5749-2022)of China.This method was featured with simple operation,fast analysis speed,high sensitivity,and good accuracy,providing an efficient and reliable technical support for routine monitoring of HAAs contaminants in drinking water and showing promising application value for widespread promotion.

Objective To investigate the therapeutic efficacy of Huangqi Guizhi Wuwu Decoction combined with monosialotetrahexosyl ganglioside(GM1)in the treatment of spinal cord injury(SCI)and to observe its effect on neuritin and neurofilament light chain protein(NFL).Methods A retrospective study was carried out in 100 cases of SCI patients.The patients admitted to Baoji Hospital of Traditional Chinese Medicine and Baoji People's Hospital from February 2022 to May 2024 were divided into a control group and a study group according to the treatment method,with 50 patients in each group.The control group was given GM1 combined with methylprednisolone,and the study group was given Huangqi Guizhi Wuwu Decoction combined with GM1.The course of treatment covered three weeks.Before and after the treatment,the two groups were observed in the changes of traditional Chinese medicine(TCM)syndrome scores,American Spinal Injury Association(ASIA)scores for evaluating the degree of spinal cord injury,Modified Ashworth Spasticity Scale(MASS)and Manual Muscle Testing(MMT)scores for assessing muscle tone and muscle strength,scores of Functional Ambulation Category Scale(FAC)and Lower-Extremity Motor Subscale(LEMS)of ASIA for assessing lower extremity motor function,and serum levels of neuron-specific enolase(NSE),glial fibrillary acidic protein(GFAP),nerve growth factor(NGF),S100B protein(S100B),Neuritin,and NFL.After treatment,the clinical efficacy and the incidence of complications in the two groups were compared.Results(1)After three weeks of treatment,the total effective rate of the study group was 90.00%(45/50)and that of the control group was 74.00%(37/50),and the intergroup comparison(tested by chi-square test)showed that the clinical efficacy of the study group was significantly superior to that of the control group(P<0.05).(2)After treatment,the two groups presented a decrease in the scores of TCM symptoms of limb numbness,limb paralysis,dysuria,irregular defecation,pale complexion,swelling and pain at injured spot,palpitation and spontaneous sweating,and shortness of breath and fatigue when compared with those before treatment(P<0.05),and the decrease of the scores in the study group was significantly superior to that in the control group(P<0.01).(3)After treatment,the evaluation of ASIA scores for the degree of spinal cord injury showed that the motor function,tactile and pain scores in the two group were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(4)After treatment,MASS and MMT scores for assessing muscle tone and muscle strength in the two groups were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(5)After treatment,the FAC score and LEMS scores for assessing lower extremity motor function in the two groups were increased compared with those before treatment(P<0.05),and the increase in the study group was significantly superior to that in the control group(P<0.01).(6)After treatment,the serum levels of NSE,GFAP,NGF,S100B,Neuritin,and NFL in the two groups were decreased compared with those before treatment(P<0.05),and the decrease in the study group was significantly superior to that in the control group(P<0.01).(7)The incidence of complications in the study group was 6.00%(3/50),and that in the control group was 16.00(8/50),the comparison between the two groups showed that the difference was not statistically significant(P>0.05).Conclusion Huangqi Guizhi Wuwu Decoction combined with GM1 exerts remarkable efficacy in treating patients with SCI,and is effective on relieving clinical symptoms,reducing the degree of spinal cord injury,enhancing the motor function of the lower extremitiess,and improving the muscle strength and tone.Its therapeutic mechanism may be related to the improvement of the expression level of serum factors such as Neuritin and NFL.

BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.
Animals ; Robotic Surgical Procedures/methods* ; Laparoscopy/methods*

BACKGROUND: Knee osteoarthritis (OA) is still challenging to prevent or treat. Enhanced endoplasmic reticulum (ER) stress and increased pyroptosis in chondrocytes may be responsible for cartilage degeneration. This study aims to investigate the effect of ER stress on chondrocyte pyroptosis and the upstream regulatory mechanisms, which have rarely been reported. METHODS: The expression of the histone methyltransferase enhancer of zeste homolog 2 (EZH2), microRNA-142-3p (miR-142-3p), and high mobility group box 1 (HMGB1) and the levels of ER stress, pyroptosis, and metabolic markers in normal and OA chondrocytes were investigated by western blotting, quantitative polymerase chain reaction, immunohistochemistry, fluorescence in situ hybridization, fluorescein amidite-tyrosine-valine-alanine-aspartic acid-fluoromethyl ketone (FAM-YVAD-FMK)/Hoechst 33342/propidium iodide (PI) staining, lactate dehydrogenase (LDH) release assays, and cell viability assessments. The effects of EZH2, miR-142-3p, and HMGB1 on ER stress and pyroptosis and the hierarchical regulatory relationship between them were analyzed by chromatin immunoprecipitation, luciferase reporters, gain/loss-of-function assays, and rescue assays in interleukin (IL)-1β-induced OA chondrocytes. The mechanistic contribution of EZH2, miR-142-3p, and HMGB1 to chondrocyte ER stress and pyroptosis and therapeutic prospects were validated radiologically, histologically, and immunohistochemically in surgically induced OA rats. RESULTS: Increased EZH2 and HMGB1, decreased miR-142-3p, enhanced ER stress, and activated pyroptosis in chondrocytes were associated with OA occurrence and progression. EZH2 and HMGB1 exacerbated and miR-142-3p alleviated ER stress and pyroptosis in OA chondrocytes. EZH2 transcriptionally silenced miR-142-3p via H3K27 trimethylation, and miR-142-3p posttranscriptionally silenced HMGB1 by targeting the 3'-UTR of the HMGB1 gene. Moreover, ER stress mediated the effects of EZH2, miR-142-3p, and HMGB1 on chondrocyte pyroptosis. In vivo experiments mechanistically validated the hierarchical regulatory relationship between EZH2, miR-142-3p, and HMGB1 and their effects on chondrocyte ER stress and pyroptosis. CONCLUSIONS A novel EZH2/miR-142-3p/HMGB1 axis mediates chondrocyte pyroptosis and cartilage degeneration by regulating ER stress in OA, contributing novel mechanistic insights into OA pathogenesis and providing potential targets for future therapeutic research.
Enhancer of Zeste Homolog 2 Protein/genetics* ; Osteoarthritis, Knee/pathology* ; Chondrocytes/metabolism* ; Pyroptosis/physiology* ; HMGB1 Protein/genetics* ; MicroRNAs/metabolism* ; Endoplasmic Reticulum Stress/genetics* ; Humans ; Animals ; Rats ; Male ; Rats, Sprague-Dawley ; Middle Aged

Based on the pharmacokinetics theory, this study investigated the pharmacokinetic characteristics of albiflorin, paeoniflorin, wogonoside, and wogonin in normal and febrile rats and summarized absorption and elimination rules of Dayuanyin in them to provide reference for further development and clinical application of Dayuanyin. Blood samples were taken from the fundus venous plexus of normal and model rats after intragastric administration of Dayuanyin at different time points. The concentration of each substance in blood was determined by ultra performance liquid chromatography-triple quadrupole mass spectrometry(UPLC-MS/MS) technique at different time points. DAS 2.0, a piece of pharmacokinetics software, was used to calculate the pharmacokinetic parameters of each component. The results show that the 4 components had good linear relationship in their respective ranges, and the results of methodological investigation met the requirements. The pharmacokinetic parameters of C_(max), T_(max), t_(1/2), AUC_(0-t), AUC_(0-∞), and MRT_(0-t) were calculated by the DAS 2.0 non-compartmental model. Compared with those in the normal group, C_(max) and AUC_(0-t) of the 4 components in the model group were significantly increased. There were significant differences in the pharmacokinetic characteristics between the normal and model groups, suggesting that the absorption and elimination of Dayuanyin may be affected by the changes of internal environment of the body in different physiological states.
Animals ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Rats, Sprague-Dawley ; Fever/metabolism* ; Tandem Mass Spectrometry ; Chromatography, High Pressure Liquid ; Glucosides/pharmacokinetics* ; Monoterpenes

In order to investigate whether the effect of Yuxuebi Tablets on the peripheral and central inflammation resolution of mice with inflammatory pain is related to their regulation of G protein-coupled receptor 37(GPR37), an inflammatory pain model was established by injecting complete Freund's adjuvant(CFA) into the paws of mice, with a sham-operated group receiving a similar volume of normal saline. The mice were assigned randomly to the sham-operated group, model group, ibuprofen group(91 mg·kg~(-1)), and low-, medium-, and high-dose groups of Yuxuebi Tablets(60, 120, and 240 mg·kg~(-1)). The drug was administered orally from days 1 to 19 after modeling. Von Frey method and the hot plate test were used to detect mechanical pain thresholds and heat hyperalgesia. The levels of interleukin-10(IL-10) and transforming growth factor-beta(TGF-β) in the spinal cord were quantified using enzyme-linked immunosorbent assay(ELISA), and the mRNA and protein expression of GPR37 in the spinal cord was measured by real-time quantitative reverse transcription PCR(qRT-PCR) and Western blot. Additionally, immunofluorescence was used to detect the expression of macrosialin antigen(CD68), mannose receptor(MRC1 or CD206), and GPR37 in dorsal root ganglia, as well as the expression of calcium-binding adapter molecule 1(IBA1), CD206, and GPR37 in the dorsal horn of the spinal cord. The results showed that compared with those of the sham-operated group, the mechanical pain thresholds and hot withdrawal latency of the model group significantly declined, and the expression of CD68 in the dorsal root ganglia and the expression of IBA1 in the dorsal horn of the spinal cord significantly increased. The expression of CD206 and GPR37 significantly decreased in the dorsal root ganglion and dorsal horn of the spinal cord, and IL-10 and TGF-β levels in the spinal cord were significantly decreased. Compared with those of the model group, the mechanical pain thresholds and hot withdrawal latency of the high-dose group of Yuxuebi Tablets significantly increased, and the expression of CD68 in the dorsal root ganglion and IBA1 in the dorsal horn of the spinal cord significantly decreased. The expression of CD206 and GPR37 in the dorsal root ganglion and dorsal horn of the spinal cord significantly increased, as well as IL-10 and TGF-β levels in the spinal cord. These findings indicated that Yuxuebi Tablets may reduce macrophage(microglial) infiltration and foster M2 macrophage polarization by enhancing GPR37 expression in the dorsal root ganglia and dorsal horn of the spinal cord of CFA-induced mice, so as to improve IL-10 and TGF-β levels, promote resolution of both peripheral and central inflammation, and play analgesic effects.
Inflammation/genetics* ; Pain/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Mice ; Freund's Adjuvant/pharmacology* ; Ibuprofen ; Pain Threshold/drug effects* ; Hyperalgesia/genetics* ; Ganglia, Spinal ; Interleukin-10/genetics* ; Transforming Growth Factor beta/genetics* ; Reverse Transcriptase Polymerase Chain Reaction ; Tablets ; Receptors, G-Protein-Coupled