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.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To observe the residual of lumbago and leg pain with contained type(CT)and non-contained type(NCT)lumbar disc herniation(LDH)after transforaminal endoscopic treatment,and to explore the role of hypoxia-inducible factor-1α(HIF-1α)and transient receptor potential vanillate 1(TRPV1)pathway.Methods A total of 68 single-segment LDH patients were selected from July 2021 to October 2022,including 44 males and 24 females;aged 26 to 67 years old with an av-erage of(43.63±11.94)years old;course of disease was 4 to 36(18.91±10.34)months;body mass index was(24.45±4.00)kg·m-2;there were 7 cases of L3.4 segments,32 cases of L4,5 segments,and 29 cases of L5S1 segments.All of them were per-formed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained group(CT group)and non-contained group(NCT group)with 34 cases respectively according to the integrity of outer layer of fibrous an-nulus observed during operation.A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were se-lected as control group,including 12 males and 5 females;aged 21 to 65 years old with an average of(39.41±12.80)years old;body mass index was(24.86±4.11)kg·m-2.The relative mRNA expression quantity of HIF-1α,TRPV1 in nucleus pulposus were measured by quantitative real-time PCR.The contents of neurokinin 1 receptor(NK1R),nerve growth factor(NGF),vascular endothelial growth factor(VEGF)in nucleus pulposus and the serum substance P(SP)and calcitonin gene-related peptide(CGRP)were detected by enzyme linked immunosorbent assay(ELISA).The threshold of lumbar tenderness was de-tected by a pressure pain meter.The degree of lumbago and lumbar function were evaluated by visual analog scale(VAS)and Oswestry disability index(ODI)separately.The residual rate of postoperative lumbago and leg pain was assessed.Results The mRNA relative expression quantity of HIF-1α and TRPV1,and the contents of NK1R,NGF and VEGF in nucleus pulposus,and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT group(P＜0.05),and those in the CT group were higher than the control group(P＜0.05).At day 7 after surgery,the serum SP and CGRP levels,lum-bago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery(P＜0.05),and those in the NCT group were higher than the CT group(P＜0.05),and the threshold of lumbar tenderness in the NCT group was lower than the CT group(P＜0.05).The differences of lumbago and leg pain VAS scores,lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT group(P＜0.05).The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT group(P＜0.05).Conclusion HIF-1α and TRPV1 pathway promoted the excessive production of NGF,VEGF,NK1R in nucleus pulposus and serum neuropeptides SP and CGRP,which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.

Wenzhou has improved its environmental quality because of comprehensive environmental remediation; nevertheless, the semen quality of infertile males remains unclear. This study determined whether better environmental quality improved semen quality in this region. We recorded semen quality data from 22 962 infertile males from January 2014 to November 2019 at the Center for Reproductive Health of The First Affiliated Hospital of Wenzhou Medical University (Wenzhou, China). Patients were predominantly 30-35 years old (33.1%) and workers (82.0%), with high school education or lower (77.6%); more than a half of the patients (52.6%) were Wenzhou household registration; and most patients (77.5%) had abnormal semen quality. Patients who were older than 40 years and workers, and those with Wenzhou household registration, had significantly worse semen quality (all P < 0.05). From 2014 to 2019, progressive sperm motility, total sperm motility, and semen volume showed increasing linear trends in all patients (P = 0.021, 0.030, and 0.005, respectively), yet normal sperm morphology showed a linearly decreasing trend (P = 0.046). Sensitivity analyses for subgroups yielded similar results. In conclusion, the improvement of environmental quality and better function of the accessory glands are associated with progressive sperm motility, total sperm motility, and semen volume. Normal sperm morphology is influenced by occupational exposures and personal lifestyle and does not improve with environmental quality.
Male ; Humans ; Adult ; Semen Analysis ; Semen ; Sperm Count ; Sperm Motility ; Infertility, Male ; Spermatozoa

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Rare and endangered Chinese medicinal materials are the material basis for innovation and development of Chinese medicinal materials and their curative effects are remarkable. However, the resources are in shortage due to various man-made or natural factors such as rising demand, overexploitation and environmental degradation. Therefore, finding alternatives is a feasible and effective solution. This study systematically sorted out the list of rare and endangered Chinese medicinal materials, and combed relevant policies and regulations. According to existing research, the substitution model of rare and endangered Chinese medicinal materials was constructed from the theoretical level. In view of the slow search for substitutes, the failure to follow the basic theory of traditional Chinese medicine in the process of research and development, the difficulty in breaking through technologies and the incomplete guarantee of the clinical efficacy of substitutes, a multi-component replacement was proposed to replace the originals with more effective components from a wide range of sources. This study was expected to promote the study on the substitutes of rare and endangered Chinese medicinal materials to step into a new stage.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Research Design ; Plants, Medicinal ; Medicine, Chinese Traditional ; Technology

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective To evaluate the efficacy of ultrasound and computed tomography (CT) in diagnosing cervical lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC). Methods The patients with PTC treated by surgery in the Chinese PLA General Hospital from January 2016 to January 2021 were selected for analysis.All the patients underwent preoperative ultrasound and CT examinations,the diagnostic values of which for CLNM were retrospectively analyzed. Results A total of 322 PTC patients were enrolled in this study,including 242 with CLNM and 80 with non-CLNM.The CLNM group and non-CLNM group had significant differences in age,tumor size,and maximum size of lateral CLNM (χ²=20.34,27.34,and 4.30,respectively,all P<0.001).For the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis showed higher sensitivity (χ ²=82.26,P<0.001;χ²=114.01,P<0.001;χ²=82.26,P<0.001) and accuracy (χ²=20.27,P<0.001;χ²=15.56,P<0.001;χ²=44.00,P<0.001) than CT,and had no significant differences from ultrasound combined with CT (all P>0.05).However,ultrasound diagnosis had lower specificity than CT (χ²=17.01,P<0.001;χ²=21.29,P<0.001) in the central compartment and lateral compartment.Receiver operating characteristic curve analysis showed that in the central compartment,lateral compartment,and overall compartment,ultrasound diagnosis had larger AUC than CT (Z=2.99,P=0.003;Z=3.86,P<0.001;Z=4.47,P<0.001) and had no significant difference from ultrasound combined with CT (Z=1.87,P=0.062;Z=1.68,P=0.093;Z=1.61,P=0.107). Conclusions Ultrasound and CT have their own advantages in the diagnosis of central and lateral CLNM.In general,ultrasound has better performance than CT in the diagnosis of CLNM.
Humans ; Lymphatic Metastasis/diagnostic imaging* ; Retrospective Studies ; Thyroid Cancer, Papillary/pathology* ; Thyroid Neoplasms/surgery* ; Tomography, X-Ray Computed ; Ultrasonography/methods*

To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.
Child ; Diagnosis, Differential ; Female ; Gingival Neoplasms/surgery* ; Granular Cell Tumor/surgery* ; Humans ; Male ; Pregnancy

Objective:To observe the effect of Qigesan on the proliferation and apoptosis of the human esophageal cancer cell EC9706， and the effect on miR-133a/protein kinase B（Akt）/mammalian target of rapamycin （mTOR） signaling pathway. Method:The effective constituent of Qigesan was extracted by ethyl acetate. Thiazolyl blue tetrazolium bromide（MTT） colorimetric assay was used to determine the dosage of Qigesan on cells and to detect the effect of Qigesan on the proliferation of EC9706 cells. The effect of Qigesan on apoptosis of EC9706 cells was detected by flow cytometry. The effect of Qigesan on miR-133a and insulin-like growth factor 1 receptor（IGF-1R） mRNA expression was detected by Real-time quantitative polymerase chain reaction （Real-time PCR） . The protein expression of Akt and mTOR in EC9706 cells was detected by Western blot. Result:Qigesan can inhibit the proliferation of EC9706 cells in a dose-dependent manner（P<0.01）. Inhibitory concentrations 30% inhibition concentration（IC₃₀） 40 mg·L^-1 and median inhibition concentration（IC₅₀） 80 mg·L^-1 were selected for follow-up experiments. Compared with the blank group， both the inhibitor group and the combination drug group can inhibit the proliferation of EC9706 cells （P<0.01）. The inhibitor at 0.25 μmol·L^-1 was selected for subsequent experiments. Compared with the blank group， Qigesan 80 mg·L^-1 dose group could significantly promote the late apoptosis rate and total apoptosis rate of EC9706 cells（P<0.05）， and the 40 mg·L^-1 dose group could significantly promote the late apoptosis rate of EC9706 cells（P<0.05）， which shows synergistic effect after concomitant use with Akt/mTOR inhibitor（P<0.05）. Compared with the blank control group， each group can effectively increase expression of miR-133a（P<0.05）. The combination of inhibitor and traditional Chinese medicine（TCM） has obvious promotion effect. Compared with blank control group， the expressions of Akt and mTOR were significantly decreased in each group（P<0.05）. Compared with single medication， the expressions of Akt and mTOR were decreased in combination of inhibitor and TCM group. Conclusion:Qigesan can inhibit the growth of EC9706 cells and promote apoptosis， and its inhibitory mechanism may be related to the Akt/mTOR signaling pathway by regulating the expression of miR-133a.