Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

This study investigated the effect of multi-glycosides of Tripterygium wilfordii(GTW) on renal injury in diabetic kidney disease(DKD) rats through Nod-like receptor protein 3(NLRP3)/cysteine-aspartic acid protease-1(caspase-1)/gsdermin D(GSDMD) pyroptosis pathway and the mechanism. To be specific, a total of 40 male SD rats were randomized into the normal group(n=8) and modeling group(n=34). In the modeling group, a high-sugar and high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ) were used to induce DKD in rats. After successful modeling, they were randomly classified into model group, valsartan(Diovan) group, and GTW group. Normal group and model group were given normal saline, and the valsartan group and GTW group received(ig) valsartan and GTW, respectively, for 6 weeks. Blood urea nitrogen(BUN), serum creatinine(Scr), alanine ami-notransferase(ALT), albumin(ALB), and 24 hours urinary total protein(24 h-UTP) were determined by biochemical tests. The pathological changes of renal tissue were observed based on hematoxylin and eosin(HE) staining. Serum levels of interleukin-1β(IL-1β) and interleukin-18(IL-18) were detected by enzyme-linked immunosorbent assay(ELISA). Western blot was used to detect the expression of pyroptosis pathway-related proteins in renal tissue, and RT-PCR to determine the expression of pyroptosis pathway-related genes in renal tissue. Compared with the normal group, the model group showed high levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), low level of ALB(P<0.01), severe pathological damage to kidney, and high protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01). Compared with the model group, valsartan group and GTW group had low levels of BUN, Scr, ALT, and 24 h-UTP and serum levels of IL-1β and IL-18(P<0.01), high level of ALB(P<0.01), alleviation of the pathological damage to the kidney, and low protein and mRNA levels of NLRP3, caspase-1, and GSDMD in renal tissue(P<0.01 or P<0.05). GTW may inhibit pyroptosis by decreasing the expression of NLRP3/caspase-1/GSDMD in renal tissue, thereby relieving the inflammatory response of DKD rats and the pathological injury of kidney.
Rats ; Male ; Animals ; Diabetic Nephropathies/genetics* ; Interleukin-18/metabolism* ; Glycosides/pharmacology* ; Tripterygium ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Rats, Sprague-Dawley ; Caspase 1/metabolism* ; Pyroptosis ; Uridine Triphosphate/pharmacology* ; Kidney ; Valsartan/pharmacology* ; RNA, Messenger/metabolism* ; Diabetes Mellitus

Objective:To identify clinical features,possible risk factors and treatment related to rituximab-associated interstitial pneumonia(RTX-IP). Methods:The clinicopathological characteristics,immune phenotype and treatment of six patients with diffuse large B-cell lymphoma(DLBCL)develped after receiving R-CDOP treatment were retrospectively analyzed. Results:Six patients had agranulocytosis or granulocytopenia within 1 week before RTX-IP diagnosis,and the median interval time was 3 courses of treatment.All six patients had double-expressor lymphoma(DEL)or triple-expressor lymphoma(TEL).Of the six patients,four had germinal-center B-cell-like lymphoma(GCB),and two had non-GCB.The expression of Ki-67 was＞70％,except for one patient with transformed lymphoma(TL).After treatment with methylprednisolone for about 1 week,all patients'chest CT showed inflammatory absorption.However,one patient developed pneumocystis carinii pneumonia during the process of hormone reduction,and recovered after 27 days of comprehensive treatment with hormones and anti-pneumocystosis therapy.All patients received CDOP regimen(a total of 8 courses)for the treatment of the primary disease,and the process was smooth. Conclusion:R-CDOP regimen may lead to a high incidence of RTX-IP in DLBCL patients(30.0％).The DLBCL patients with DEL or TEL,GCB subtype,TL and high Ki-67 expression were more liable to develop RTX-IP,and the recovery of agranulocytosis may be related to the pathogenesis of RTX-IP.High-resolution CT scan can provide valuable evidence for early diagnosis of RTX-IP.Metagenomic next-generation sequencing(mNGS)helps to distinguish IP from pathogen infections.High dose of glucocorticoids is effective treatment strategy.At the same time,it is necessary to strengthen the prevention and treatment of infection in the process of glucocorticoids application.

Alzheimer Disease/genetics* ; Animals ; Apolipoprotein E4/metabolism* ; Gene-Environment Interaction ; Hippocampus/metabolism* ; Male ; Noise/adverse effects* ; Rats

Objective:To study the effect of Wenjing Huayu Zhitong therapy （Xiangyan Zhitong prescription， XZP） on the mitogen activated protein kinase （MAPK）/extracelluar regulated protein kinase （ERK） signaling pathway of primary dysmenorrhea （PD） rats， and explore the pathogenesis of PD and the mechanism of action of Wenjing Huayu Zhitong therapy. Method:Forty-eight female SPF-grade Wistar rats were randomly divided into blank group，model group， western medicine group， low-dose XZP group， medium-dose XZP group， and high-dose XZP group， with 8 rats in each group. In addition to the blank group， dysmenorrhea rat model with cold coagulation and blood stasis syndrome was established by cold stimulation combined with estradiol benzoate and oxytocin. The rats in the blank group，model group，western medicine group， low-dose XZP group， medium-dose XZP group， and high-dose XZP group were given distilled water， distilled water，0.06 g·kg^-1 ibuprofen， 6.55 g·kg^-1 XZP， 13.09 g·kg^-1 XZP， and 26.18 g·kg^-1 XZP， respectively， by gavage for 6 days. The writhing latency and writhing frequency of rats were recorded within 30 min after oxytocin injection.Western blot was used to detect the protein expression of B-Raf， mitogen activates extracellular regulated kinases1/2 （MEK1/2）， extracellular regulated kinases1/2 （ERK1/2）， p-MEK1/2， p-ERK1/2， c-Jun， and cyclooxygenase-2 （COX-2） in rat uterus. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to detect the mRNA expression of B-Raf， MEK1， MEK2， ERK1， ERK2， c-Jun， and cyclooxygenase-2 （COX-2） in rat uterus. Result:Compared with the model group，the treatment groups showed insignificantly prolonged writhing latency and significantly reduced writhing frequency （P<0.01）. On the 6^th day of modeling， there was no significant difference in the quantitative scores of symptoms and signs among the treatment groups. On the 12^th day of modeling， the scores changed little in the western medicine group and the low-dose XZP group and decreased significantly in the medium- and high-dose XZP groups （P<0.01） compared with those in the model group. Compared with those in the blank group， the protein and mRNA levels of p-MEK1/2， p-ERK， B-Raf， c-Jun， and COX-2 in the model group were significantly up-regulated （P<0.01）. Compared with those in the model group， the protein and mRNA levels of p-MEK1/2， p-ERK1/2， B-Raf， c-Jun， and COX-2 in the western medicine group， medium-dose XZP group， and high-dose XZP group were significantly down-regulated （P<0.05，P<0.01）. Conclusion:The mechanism of Wenjing Huayu Zhitong therapy in treating PD with cold coagulation and blood stasis syndrome may be related to the down-regulation of MAPK/ERK signaling pathway.

OBJECTIVE: To provide a comprehensive and contemporary overview of the long-term safety outcomes after aortic valve replacements (AVR) with conventional biological heart valve (stented or stentless). METHODS: English databases (Medline, Embase, Web of Science, CENTRAL, and ClinicalTrial.gov) and Chinese databases (CNKI, VIP, WanFang, and SinoMed) were searched systemically from January 1, 2000 to January 26, 2019. Eligible randomized controlled trials, non-randomized clinical trials, cohort studies (retrospective or prospective), and unselected case series were included. Strict screening of the obtained literature was conducted to extract relevant data by two reviewers. Other inclusion criteria were studied reporting on outcomes of AVR with biological valves (stented or stentless), with or without coronary artery bypass grafting (CABG) or valve repair procedure, with mean follow-up length equal to or longer than 5 years. We excluded studies that reported only a specific patient group (e.g., patients with renal failure, or pregnancy), without the report of biological valve type, or with study population size less than 100. The meta-analysis was performed using Stata 14.0 software. RESULTS: In this study, 53 papers (in total 57 study groups) involving 47 803 patients were included. (1) The all-cause mortality was 6.33/100 patient-years (95%CI: 5.85-6.84). Subgroup analysis showed that the mortality rates of porcine and bovine valve prostheses were 5.69/100 patient-years (95%CI: 5.05-6.41) and 7.29/100 patient-years (95%CI: 6.53-8.13), respectively. The all-cause mortality rates for stented and stentless valve were 6.69/100 patient-years (95%CI: 6.12-7.30) and 5.21/100 patient-years (95%CI: 4.43-6.14), respectively. (2) The incidence rate of thromboembolism was 1.16/100 patient-years (95%CI: 0.96-1.40), the incidence rate of permanent pacemaker (PPM) implantation was 1.08/100 patient-years (95%CI: 0.75-1.54), the incidence rate of stroke was 0.74/100 patient-years (95%CI: 0.51-1.06), the incidence rate of structural valve dysfunction (SVD) was 0.73/100 patient-years (95%CI: 0.59-0.91), the incidence rate of major bleeding was 0.52/100 patient-years (95%CI: 0.41-0.65), the incidence rate of endocarditis was 0.38/100 patient-years (95%CI: 0.33-0.44), and the incidence rate of non-structural valve dysfunction (NSVD) was 0.20/100 patient-years (95%CI: 0.13-0.31). The total reoperation rate for biological aortic valve was 0.77/100 patient-years (95%CI: 0.65-0.91), and the SVD related reoperation rate was 0.46/100 patient-years (95%CI: 0.36-0.58). CONCLUSION The all-cause mortality for conventional biological AVR was 6.33/100 patient-years. Thromboembolism, PPM implantation, reoperation, stroke, and SVD were major long term complications.
Animals ; Aortic Valve ; Cattle ; Heart Valve Prosthesis Implantation ; Humans ; Prospective Studies ; Prosthesis Design ; Reoperation ; Retrospective Studies ; Swine ; Treatment Outcome

OBJECTIVE: To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit. METHODS: Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively. RESULTS: The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups (>0.05); the total score of MMSE after treatment was higher than that before treatment (both <0.05); compared before treatment, the short-term memory score was increased in the treatment group (<0.05), and the increasing range was superior to that in the control group (<0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both <0.05), and the reduction in the treatment group was less than that in the control group (<0.05); the differences of short-term memory score before and after treatment was significant between the two groups (<0.05). No adverse reaction occurred in the two groups. CONCLUSION The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.
Acupuncture Points ; Acupuncture Therapy ; Alzheimer Disease ; psychology ; therapy ; Case-Control Studies ; Electroacupuncture ; Humans ; Mental Status and Dementia Tests

OBJECTIVETo investigate the effects of bortezomib(BTZ) and thalidomide(TM) on peripheral blood memory T-cells (T) and regulatory T cells(Tregs) in patients with multiple myeloma(MM).

METHODSEighty-six MM patients received 2 courses of chemotherapy were divided into effective (partial response at least) group (63 cases) and ineffective (no partial response) group (17 cases) according to therapeutic efficacy; these 80 patients were divided into BTZ group (38 cases) and TM group (42 cases) yet according to therapeutic regimens, 20 newly diagnosed MM patients were used as baseline group, 30 healthy volunteers were used as healthy control group. The T subsets and Treg in peripheral blood of each groups were detected by flow cytometry.

RESULTSThe CD4 central memory T cells (CD4 T) percentage of CD4 T, the CD18 T percentage of CD18T and ratio of CD8 T and CD8 effector memory T cells (T) (CD8 T/T) in baseline group were all significantly lower than those in healthy control group (P<0.05). After treatment with BTZ regimen or TM regimen, the CD8T percentage of CD8 T in effective group significantly increased to level of healthy control group (P<0.05); the Treg cell level in effective and in effective groups was not significantly different from that in baseline group(P>0.05), but the Treg percentage of CD4 cells ineffective group was significantly higher than that in baseline group and ineffective group (P<0.05). According to ROC curve, the critical value of CD8T/T for predicting chemotherapeutic response was 0.27 with sensitivity of 57.1% and specificity of 94.1%.

CONCLUSIONWhen MM patients are in an immuno-exhanstive status, the treatment with BTZ or TM both can reverse the immuno-inhibitory status of MM patients, moreover, does not affect the Treg cell count; the Treg percentage in BTZ and TM effective groups both are significantly higher than that in baseline group and ineffective group. The ratio of CD8T/T contributes to evaluating the chemotherapeutic efficacy.

Traditional Chinese medicine (TCM) is an important part of the treatment of primary liver cancer (PLC) in China; however, the current instructions for the integrative use of traditional Chinese and Western medicine for PLC are mostly based on expert opinion. There is no evidence-based guideline for clinical practice in this field. Therefore, the Shanghai Association of Chinese Integrative Medicine has established a multidisciplinary working group to develop this guideline, which focuses on the most important questions about the use of TCM during PLC treatment. This guideline was developed following the methodological process recommended by the World Health Organization Handbook for Guideline Development. Two rounds of questionnaire survey were performed to identify clinical questions; published evidence was searched; the Grading of Recommendations Assessment, Development and Evaluation approach was used to evaluate the body of evidence; and recommendations were formulated by combining the quality of evidence, patient preferences and values, and other risk factors. The guideline was written based on the Reporting Items for Practice Guidelines in Healthcare tool. This guideline contains 10 recommendations related to 8 questions, including recommendations for early treatment by TCM after surgery, TCM combined with transcatheter arterial chemoembolization for advanced PLC, TCM drugs for external use, and acupuncture and moxibustion therapy.
Acupuncture Therapy ; Amphibian Venoms ; therapeutic use ; China ; Combined Modality Therapy ; standards ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Integrative Medicine ; standards ; Liver Neoplasms ; drug therapy ; pathology ; therapy ; Medicine, Chinese Traditional ; standards ; Neoplasm Staging ; Practice Guidelines as Topic

Nanopore / nanochannel sensing technique drawing more attention in analytical chemistry due to its unique advantages and the fabricated electrochemical sensors and electrochemical responsive gates have been widely used for more target detection, including single molecule protein and DNA sequencing. Nanopore /nanochannel that used for fabricating electrochemical detection system is mainly divided into biological nanopore and solid state nanopore, and among them, solid state nanopore / nanochannel has a wide range of application due to its inherent properties, such as easy for modification, good mechanical property and stability. Resistive pulse sensing and current-voltage curves (ion current rectification) are two main methods of nanopore / nanochannel sensing technique used for target analysis, so in this review, we introduced the fundamentals and applications of nanopore sensing technique based on the above two methods. In addition, we concluded the application and development of single state nanopore / nanochannel in recent years, and also gave a brief look at the future challenges and prospects in the development of this field.