ObjectiveTo investigate the mechanism of Acanthopanacis Senticosi Radix et Rhizoma seu Caulis extract （ASH） in treating Parkinson's disease （PD） in mice by Data-Independent Acquisition （DIA） proteomics. MethodsThe α-Synuclein （α-Syn） transgenic PD mice were selected as suitable models for PD， and they were randomly assigned into PD， ASH （61.25 mg·kg^-1）， and Madopar （97.5 mg·kg^-1） groups. Male C57BL/6 mice of the same age were selected as the control group， with eight mice in each group. Mice were administrated with corresponding drugs by gavage once a day for 20 days. The pole climbing time and the number of autonomic activities were recorded to evaluate the exercise ability of mice. Hematoxylin-eosin staining was employed to observe neuronal changes in the substantia nigra of PD mice. Immunohistochemistry （IHC） was employed to measure the tyrosine hydroxylase （TH） activity in the substantia nigra and assess the areal density of α-Syn in the striatum. DIA proteomics was used to compare protein expression in the substantia nigra between groups. IHC was utilized to validate key differentially expressed proteins， including Lactotransferrin， Notch2， Ndrg2， and TMEM 166. The cell counting kit-8 （CCK-8） method was used to investigate the effect of ASH on the viability of PD cells with overexpression of α-Syn. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were employed to determine the protein and mRNA levels of Lactotransferrin， Notch2， Ndrg2， and TMEM 166 in PD cells. ResultsCompared with the control group， the model group showed prolonged pole climbing time， diminished coordination ability， reduced autonomic activities （P<0.01）， and reduced swelling neurons. Compared with the model group， ASH and Madopar reduced the climbing time， increased autonomic activities （P<0.01）， and ameliorated neuronal damage. Compared with the control group， the model group showed a decrease in TH activity in the substantia nigra and an increase in α-Syn accumulation in the striatum （P<0.01）. Compared with the model group， the ASH group showed an increase in TH activity and a reduction in α-Syn accumulation （P<0.05）. DIA proteomics revealed a total of 464 differentially expressed proteins in the model group compared with the control group， with 323 proteins being up-regulated and 141 down-regulated. A total of 262 differentially expressed proteins were screened in the ASH group compared with the model group， including 85 proteins being up-regulated and 177 down-regulated. Kyoto encylopedia of genes and genomes （KEGG） pathway analysis indicated that ASH primarily regulated the Notch signaling pathway. The model group showed up-regulation in protein levels of Notch2， Ndrg2， and TMEM 166 and down-regulation in the protein level of Lactotransferrin compared with the control group （P<0.01）. Compared with the model group， ASH down-regulated the protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.05） while up-regulating the protein level of Lactotransferrin （P<0.01）. The IHC results corroborated the proteomics findings. The cell experiment results showed that compared with the control group， the modeling up-regulated the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while down-regulating the mRNA and protein levels of Lactotransferrin （P<0.01）. Compared with the model group， ASH reduced the mRNA and protein levels of Notch2， Ndrg2， and TMEM 166 （P<0.01）， while increasing the mRNA and protein levels of Lactotransferrin （P<0.05， P<0.01）. ConclusionASH may Synergistically inhibit the Notch signaling pathway and mitigate neuronal damage by down-regulating the expression of Notch2 and Ndrg2. Additionally， by up-regulating the expression of Lactotransferrin and down-regulating the expression of TMEM166， ASH can address brain iron accumulation， intervene in ferroptosis， inhibit mitophagy， and mitigate reactive oxygen species damage， thereby protecting nerve cells and contributing to the treatment of PD.

Pyroptosis is the programmed death of cells accompanied by an inflammatory response and is widely involved in the development of a variety of diseases, such as infectious diseases, cardiovascular diseases, and neurodegeneration. It has been shown that cellular scorching is involved in the pathogenesis of pulmonary arterial hypertension ( PAH) in cardiovascular diseases. Patients with PAH have perivascular inflammatory infiltrates in lungs, pulmonary vasculopathy exists in an extremely inflam-matory microenvironment, and pro-inflammatory factors in cellular scorching drive pulmonary vascular remodelling in PAH patients. This article reviews the role of cellular scorch in the pathogenesis of PAH and the related research on drugs for the treatment of PAH, with the aim of providing new ideas for clinical treatment of PAH.

There seems to be a contradiction among the symptoms of"non-thirst"and"thirst after oral use of the decoction"stated in original text 41 of Shang Han Lun(Treatise on Febrile Diseases)and the symptom of"probable thirst"stated in original text 40.In this article,the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction were expounded through the analysis of the basic theories of traditional Chinese medicine about body fluid metabolism and the pathogenic mechanism of thirst,and by synthesizing the relevant articles recorded in Jin Gui Yao Lve(Synopsis of the Golden Chamber)and the understanding of the syndrome of Xiao Qinglong Decoction by later generations of practitioners.After that,the following views are put forward:non-thirst symptom is the primary sympton of the syndrome of Xiao Qinglong Decoction,which results from the disease;thirst after oral use of the decoction is due to drug-induced thirst,which can be classified into the category of physiological thirst;probable thirst symptom is related with fluid consumption by febrile disease,indicating that the disease involves yangming.The analysis of the symptoms of thirst or non-thirst in the syndrome of Xiao Qinglong Decoction is helpful for evaluation of therapeutic efficacy,and can also be used as the indications of modified medications and differential diagnosis of the disease.The exploration will provide references for the clinical use of Xiao Qinglong Decoction and will be beneficial to improving the clinical efficacy of Xiao Qinglong Decoction.

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

ObjectiveThis study aimed to develop a novel method for encapsulating oocytes in sodium alginate hydrogel using microfluidics, then to vitrify these encapsulated oocytes in a single-step process with low concentrations of cryoprotectants. MethodsWe utilized a flow-focusing microfluidic chip to generate sodium alginate hydrogel microspheres. The influence of various parameters, including throat structure, cross-linking method, sodium alginate concentrations, and flow rate ratios on the stability diameter, and coefficient of variation of microspheres were examined. To further investigate the cold-resistance of these microspheres, we used cryomicroscopy to observe changes in volume and morphology of microspheres during cooling and warming processes. We used microfluidic chip to encapsulate oocytes in sodium alginate hydrogel microspheres, the empty rate of microspheres and loss rate of oocytes were determined. After releasing from microspheres and parthenogenetic activation with cytochalasin B and strontium chloride, the survival, cleavage and blastocyst rates were evaluated during in vitro maturation. Finally, oocytes encapsulated in sodium alginate microspheres were vitrified with low concentrations of cryoprotectants. We compared the survival and development capability of the oocytes with the Cryotop method. ResultsWhen the throat of the microfluidic chip measures 300 μm in length and 120 μm in width, microspheres can be uniformly formed at the throat of the chip. Sodium alginate generates microspheres with a wide size distribution when cross-linking outside the chip, while internal cross-linking within the chip results in more uniform microspheres. The stability of microsphere formation is significantly improved with the use of a three-channel internal cross-linking chip. At a flow rate of 2 μl/min and with 1% sodium alginate, the microfluidic chip can consistently and uniformly produce microspheres. Under flow rate ratios of 10, 15, and 20, the average microsphere diameters are 262.71 μm, 193.63 μm, and 156.63 μm, respectively. The sodium alginate hydrogel microspheres maintained their volume and structural integrity during the cooling and warming processes. Using a three-channel internal cross-linking microfluidic chip to encapsulate oocytes, at a flow rate ratio of 10, the empty rate is 32.28%, and the cell loss rate is 11.09%. After encapsulation and subsequent release, the oocyte survival rate (96.99%), cleavage rate (88.71%), and blastocyst formation rate (26.29%) showed no significant differences compared to the fresh group. After the microspheres were vitrified using a low concentration of cryoprotectant (10% DMSO+10% ehylene glycol (EG)+0.5 mol/L trehalose), the survival rate, cleavage rate, and blastocyst rate were 92.48%, 70.80%, and 20.42%, respectively. No significant difference was observed when compared to the Cryotop method using a higher concentration of cryoprotectant solution (15% DMSO+15% EG+0.5 mol/L trehalose). ConclusionWe designed and fabricated a microfluidic system with three-channel internal cross-linking chips used for oocyte vitrification preservation. The microfluidic system can generate oocytes-loaded sodium alginate hydrogel microspheres with uniform size, low empty rate, and good cold-resistance. The method successfully reduced the concentration of cryoprotectants in a single-step vitrification process, the developmental capability of oocytes during in vitro maturation were comparable with Cryotop method. Unlike the Cryotop method, the oocytes encapsulated in hydrogel does not come into contact with liquid nitrogen, eliminating the risk of cross-contamination. This study provides a novel approach to oocyte vitrification.

RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.

Objective To observe the effect of remifentanil-based fast-track anesthesia on the quality of anesthesia recovery in children with congenital heart disease underwent transcatheter closure.Methods Children with congenital heart disease who underwent transcatheter closure were divided into treatment group and control group according to the anesthesia plan.The anesthesia plan of the control group was as follows:anesthesia induction(intramuscular injection of ketamine at 4 mg·kg-1,intravenous injection of propofol at 2.5 mg·kg-1,fentanyl at 10 μg·kg-1and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(fentanyl at0.4μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).The anesthesia plan of the treatment group was as follows:anesthesia induction(intramuscular injection of ketamine at 5 mg·kg-,intravenous injection of midazolam at 0.1 mg·kg-1,sufentanil at 1.0 μg·kg-1 and cisatracurium at 0.1 mg·kg-1)and anesthesia maintenance(remifentanil at 0.5 μg·kg-1·min-1 and propofol at 8 μg·kg-1·min-1).Anesthesia recovery,facial expression,leg posture,activity,crying and comfortability(FLACC)of 5 pain scores,Ramsay score,hemodynamics,myocardial injury indexes,and adverse drug reactions were compared between the two groups.Results There were 64 cases in treatment group and 56 cases in control group.The spontaneous respiration recovery time,call time and extubation time of the treatment group were(4.87±1.22),(10.16±2.58)and(12.55±3.19)min,shorter than those in control group,which were(5.49±1.35),(13.34±3.27)and(15.67±3.62)min(all P＜0.05).At 1 h and 2 h after operation,Ramsay scores of treatment group were 2.58±0.35 and 3.69±0.42,were lower than 3.02±0.47 and 4.24±0.39 in control group(all P＜0.05).At 1 h and 2 h after operation,the FLACC scores of the treatment group were 3.03±0.81 and 3.75±0.84,lower than 3.78±0.62 and 4.36±0.51 in control group(all P＜0.05).Mean arterial pressure(MAP)of treatment group at the insertion of laryngeal mask,the insertion of occluder and the end of the operation were(102.45±10.26),(94.18±8.37)and(91.46±10.15)mmHg,lower than those in control group,which were(107.84±10.11),(100.57±9.84)and(97.33±8.53)mmHg(all P＜0.05).On day 1 and day 3 after operation,serum creatine kinase isoenzyme(CK-MB)levels in the treatment group were(10.03±2.58)and(8.65±2.16)U·L-1,lower than those in control group,which were(12.44±3.07)and(10.16±2.35)U·L-1(all P＜0.05).On day 1 and day 3 after operation,serum cardiac troponin Ⅰ(cTn Ⅰ)levels in treatment group[(0.07±0.02)and(0.04±0.01)μg·L-1]were lower than those in control group[(0.09±0.03)and(0.06±0.02)μg·L-1](all P＜0.05).The incidence of adverse anesthesia reactions in treatment group was 6.25％(4 cases/64 cases),lower than 17.86％(10 cases/56 cases)in control group(P＜0.05).Conclusion Remifentanil-based fast-track anesthesia can improve the quality of anesthesia recovery in children with congenital heart disease undergoing transcatheter closure,with good sedative and analgesic effects,stable hemodynamics during operation,and low incidence of adverse drug reactions.

Adequate inflammation can effectively eliminate harmful substances and prevent disease as a self-protective measure to prevent further damage to the body,while abnormally activated inflammation is detrimental to the body.Nucleotide binding and oligomerization domain-like receptor protein 3(NLRP3)inflammasome that participates in inflammatory responses are closely related to many physiological and pathological processes and play an important role in the occurrence and development of pulmonary diseases.This article mainly reviewed the activation mechanism and hypothesis of NLRP3 inflammasome,as well as the research on treating respiratory diseases by interfering with NLRP3 inflammasome.

Objective China is among the 30 countries with a high burden of tuberculosis(TB)worldwide,and TB remains a public health concern.Kashgar Prefecture in the southern Xinjiang Autonomous Region is considered as one of the highest TB burden regions in China.However,molecular epidemiological studies of Kashgar are lacking. Methods A population-based retrospective study was conducted using whole-genome sequencing(WGS)to determine the characteristics of drug resistance and the transmission patterns. Results A total of 1,668 isolates collected in 2020 were classified into lineages 2(46.0%),3(27.5%),and 4(26.5%).The drug resistance rates revealed by WGS showed that the top three drugs in terms of the resistance rate were isoniazid(7.4%,124/1,668),streptomycin(6.0%,100/1,668),and rifampicin(3.3%,55/1,668).The rate of rifampicin resistance was 1.8%(23/1,290)in the new cases and 9.4%(32/340)in the previously treated cases.Known resistance mutations were detected more frequently in lineage 2 strains than in lineage 3 or 4 strains,respectively:18.6%vs.8.7 or 9%,P<0.001.The estimated proportion of recent transmissions was 25.9%(432/1,668).Multivariate logistic analyses indicated that sex,age,occupation,lineage,and drug resistance were the risk factors for recent transmission.Despite the low rate of drug resistance,drug-resistant strains had a higher risk of recent transmission than the susceptible strains(adjusted odds ratio,1.414;95%CI,1.023-1.954;P = 0.036).Among all patients with drug-resistant tuberculosis(DR-TB),78.4%(171/218)were attributed to the transmission of DR-TB strains. Conclusion Our results suggest that drug-resistant strains are more transmissible than susceptible strains and that transmission is the major driving force of the current DR-TB epidemic in Kashgar.

Purpose::To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.Methods::This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log 2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay. Results::Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.Conclusions::Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.