OBJECTIVE: The aim of this study is to analyze the clinical features and genetic etiology of a patient with multiple morphological abnormalities of the sperm flagella (MMAF) retrospectively. METHODS: A severely oligospermic patient from the Reproductive Center of the First Affiliated Hospital of Ningbo University was selected as the study subject. Clinical data and examination results were collected. High-throughput sequencing and bioinformatics were used to analyze the genetic etiology. And Sanger sequencing was employed to validate findings in the family. Transmission electron microscopy (TEM) was used to observe the sperm ultrastructure, and immunofluorescence analysis was performed to examine the localization of FSIP2 protein in the sperm. RESULTS: The patient presented with severe oligospermia, and sperm morphology displayed MMAF. TEM revealed fibrous sheath and 9+2 microtubule structural disruptions in the sperm. Sequencing identified compound heterozygous variants in the FSIP2 gene (c.17798C > T, c.5927T > G), inherited from the father and mother, respectively. According to the guidelines of the American College of Medical Genetics and Genomics, the variants were classified as pathogenic. The patient's spouse underwent intracytoplasmic single sperm injection, resulting in one embryo, but no clinical pregnancy occurred after embryo transfer. CONCLUSION This study reported the mutation of FSIP2 gene c.17798C > T, c.5927T > G in a patient with MMAF. These findings expand the mutational spectrum of the FSIP2 gene and provide insights for genetic and assisted reproductive counseling for patients with MMAF.
Humans ; Male ; Sperm Tail/pathology* ; Heterozygote ; Oligospermia/genetics* ; Spermatozoa ; Mutation ; Infertility, Male/genetics* ; Adult ; Pedigree ; Retrospective Studies ; Sperm Injections, Intracytoplasmic

OBJECTIVES: To explore the mechanism by which astragaloside IV (AS-IV) alleviates D-galactose (D-GAL)-induced senescence in human umbilical vein endothelial cells (HUVECs). METHODS: Cultured HUVECs were treated with D-GAL (40 g/L), AS-IV (200 μmol/L), D-GAL+AS-IV, or D-GAL+AS-IV+MTK458 (a mitochondrial autophagy agonist, 25 μmol/L) for 48 h, and the changes in cell proliferation, migration, and angiogenesis capacity were evaluated. Cell apoptosis, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and expressions of autophagy-related proteins (LC3-II/LC3-I) and PINK1/Parkin pathway proteins in the treated cells were detected. RESULTS: AS-IV treatment significantly reduced the inhibitory effect of D-GAL on HUVEC viability, effectively alleviated D-GAL-induced impairment of tube-forming ability, and promoted angiogenesis and migration ability of the cells. AS-IV also significantly reduced the rate of D-GAL-induced HUVECs positive for senescence-associated β-galactosidase (SA-β-Gal) staining and inhibited the expression of senescence-related genes P21 and P53. AS-IV restored mitochondrial membrane potential and reduced intracellular ROS levels in D-GAL-induced HUVECs, and inhibited the fusion of autophagosomes and lysosomes to prevent the completion of autophagic flux. In HUVECs treated with both D-GAL and AS-IV, the application MTK458 significantly increased the number of yellow spots and enhanced the expressions of P21, P53, PINK1, Parkin, LC3, and Beclin proteins. CONCLUSIONS AS-IV alleviates D-GAL-induced endothelial cell senescence by inhibiting the PINK1/Parkin pathway to regulate mitochondrial autophagy.
Humans ; Human Umbilical Vein Endothelial Cells/drug effects* ; Cellular Senescence/drug effects* ; Autophagy/drug effects* ; Saponins/pharmacology* ; Ubiquitin-Protein Ligases/metabolism* ; Mitochondria/drug effects* ; Triterpenes/pharmacology* ; Protein Kinases/metabolism* ; Galactose/pharmacology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects* ; Cells, Cultured ; Apoptosis/drug effects* ; Membrane Potential, Mitochondrial ; Cell Proliferation/drug effects*

Exploring the risk "time interval window" of sequential medication of Reduning injection (RDN) and penicillin G injection (PG) by detecting the correlation between serum biochemical indexes and plasma metabonomic characteristics, in order to reduce the risk of adverse reactions caused by the combination of RDN and PG. 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). The changes of biochemical indexes in serum of rats were detected by enzyme-linked immunosorbent assay. It was determined that RDN combined with PG could cause pseudo-allergic reactions (PARs) activated by complement pathway. Further investigation was carried out at different time intervals (1.5, 2, 3.5, 4, 6, and 8 h PG+RDN). It was found that sequential administration within 3.5 h could cause significant PARs. However, PARs were significantly reduced after administration interval of more than 4 h. LC-MS was used for plasma metabolomics analysis, and the levels of serum biochemical indicators and plasma metabolic profile characteristics were compared in parallel. 22 differential metabolites showed similar or opposite trends to biochemical indicators before and after 3.5 h. And enriched to 10 PARs-related pathways such as arachidonic acid metabolism, steroid hormone biosynthesis, linoleic acid metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In conclusion, there is a risk "time interval window" phenomenon in the adverse drug reactions caused by the sequential use of RDN and PG, and the interval medication after the "time interval window" can significantly reduce the risk of adverse reactions.

Objective To observe the clinical efficacy and safety of lupatadine tablets combined with azelastine hydrochloride nasal spray in the treatment of allergic rhinitis patients.Methods Patients with allergic rhinitis were randomly divided into control group and treatment group.Both groups received general treatment.On this basis,the control group was given azelastine hydrochloride nasal spray 0.14 mg per nostril each time,bid;on the basis of control group,the treatment group received lupatadine tablets 10 mg each time,orally,qd.Two groups were treated for 4 weeks.The clinical efficacy,rhinoconjunctivitis related quality of life questionnaire(RQLQ),serum indexes[interleukin-6(IL-6),IL-1 β,tumor necrosis factor-α(TNF-α),immunoglobulin E(IgE)]and safety were compared between the two groups.Results Treatment group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.Control group were enrolled 53 cases,4 cases dropped out,and 49 cases were finally included in the statistical analysis.After treatment,the total effective rates of the treatment and control groups were 95.92％(47 cases/49 cases)and 81.63％(40 cases/49 cases)with significant difference(P＜0.05).After treatment,the RQLQ scores of treatment and control groups were(49.57±6.97)and(58.18±7.78)points,IL-6 levels were(5.12±1.25)and(7.34±1.46)ng·L-1,IL-1 β levels were(12.25±5.64)and(20.05±6.32)pg·mL-1,TNF-α levels were(3.25±0.62)and(4.45±0.49)pg·mL-1,the IgE levels were(114.28±19.63)and(136.84±30.14)μg·L-1,respectively,the differences were statistically significant difference(all P＜0.05).The adverse drug reactions of two groups were dry mouth,fatigue,dizziness and drowsiness.The total incidences of adverse drug reactions in the treatment and control groups were 16.33％and 10.20％without significant difference(P＞0.05).Conclusion Lupatadine tablets combined with azostine hydrochloride nasal spray have a definitive clinical efficacy in the treatment of allergic rhinitis patients,which can effectively reduce the inflammatory reaction,reduce the IgE levels,improve the quality of life,without increasing the incidence of adverse drug reactions.

Objective To investigate the effect of Qufu Shengji ointment combined with ulinastatin in the treatment of wound healing after perianal surgery and its effect on the level of inflammatory factors.Methods Patients who underwent perianal surgery in Guilin Hospital of Integrated Traditional Chinese and Western Medicine from July 2020 to January 2022 were randomly divided into control group and test group.The patients in both groups were treated with conventional debridement therapy and ulinastatin,and the test group was treated with Qufu Shengji ointment.The wound healing efficacy,TCM symptom score,inflammatory factor level,growth factor level and treatment safety of the two groups were compared.Results A total of 116 patients were included in the study,including 58 patients in the test group and 58 in the control group.The total effective rate of the test group(91.38％)was higher than that of the control group(75.86％),and the difference was statistically significant(P＜0.05).After treatment,the TCM syndrome score levels of interleukin-17A(IL-17A),C-reactive protein(CRP)and serum amyloid A(SAA)in the test group were lower than those in the control group(P＜0.05).The levels of vascular endothelial growth factor receptor 1(VEGFR1),fibroblast growth factor receptor(FGFR)and transforming growth factor-β1(TGF-β1)were higher than those in the control group(P＜0.05).The anal function index was higher than that of the control group(P＜0.05).The incidence of adverse reactions between the two groups was 13.79％and 8.62％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion The effect of Qufu Shengji ointment combined with ulinastatin in the treatment of wound healing after perianal surgery is significant,which can improve the TCM syndrome,reduce inflammatory factors,and upregulate growth factors,and has good safety.

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 explore the postmortem diffusion rule of Aconitum alkaloids and their metabo-lites in poisoned rabbits,and to provide a reference for identifying the antemortem poisoning or post-mortem poisoning of Aconitum alkaloids.Methods Twenty-four rabbits were sacrificed by tracheal clamps.After 1 hour,the rabbits were administered with aconitine LD50 in decocting aconite root powder by intragastric administration.Then,they were placed supine and stored at 25℃.The biological samples from 3 randomly selected rabbits were collected including heart blood,peripheral blood,urine,heart,liver,spleen,lung and kidney tissues at 0 h,4 h,8 h,12 h,24 h,48 h,72 h and 96 h after intragastric administration,respectively.Aconitum alkaloids and their metabolites in the biological samples were ana-lyzed by high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS).Results At 4 h after intragastric administration,Aconitum alkaloids and their metabolites could be detected in heart blood,peripheral blood and major organs,and the contents of them changed dynamically with the preservation time.The contents of Aconitum alkaloids and their metabolites were higher in the spleen,liver and lung,especially in the spleen which was closer to the stomach.The average mass fraction of benzoylmesaconine metabolized in rabbit spleen was the highest at 48 h after intragastric administration.In contrast,the contents of Aconitum alkaloids and their metabolites in kidney were all lower.Aconi-tum alkaloids and their metabolites were not detected in urine.Conclusion Aconitum alkaloids and their metabolites have postmortem diffusion in poisoned rabbits,diffusing from high-content organs(stomach)to other major organs and tissues as well as the heart blood.The main mechanism is the dispersion along the concentration gradient,while urine is not affected by postmortem diffusion,which can be used as the basis for the identification of antemortem and postmortem Aconitum alkaloids poisoning.

Objective To compare the oral cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator to provide references for users.Methods Ninety identical 3D-printed resin tooth models were grouped and subjected to repeated experiments,which were divided randomly into five groups including a microbubble toothbrush high-speed gear(GN-H)group,a microbubble toothbrush medium-speed gear(GN-M)group,a microbubble low-speed gear(GN-L)group,a conventional pulsed oral irrigator high-speed gear(W-H)group and a conventional pulsed oral irrigator low-speed gear(W-L)group,with 18 teeth in each group.The cleansing effects of the microbubble toothbrush and the conventional pulsed oral irrigator were evaluated in terms of irrigating strength and abilities for eliminating plaque and debris.Results Both the two types of water flossers were provided with high irrigating strength and effectively reduced plaque and debris on tooth surfaces,and the GN-H,GN-M and GN-L groups behaved better significantly than the remained groups.The order of the five groups was GN-H group＞GN-M group＞W-H group＞GN-L group＞W-L group for irrigating strength,GN-H group＞GN-M group＞GN-L group＞W-H group＞W-L group for plaque removal,GN-H group＞GN-M group＞W-H group＞GN-L group＞W-L group for debris removal,with all the differences being statistically significant(P＜0.05).Conclusion Both the two types of water flossers remove plaque and debris effectively,while the microbubble toothbrush gains advantages over the conventional pulsed oral irrigator.[Chinese Medical Equipment Journal,2024,45(9):67-72]

Objective To observe the clinical efficacy of Sanjiao Tiaoqi Acupuncture in the treatment of post-stroke respiratory dysfunction.Methods Seventy-two patients with post-stroke respiratory dysfunction were randomly divided into observation group and control group,36 cases in each group.The control group was given routine treatment,and the observation group was treated with Sanjiao Tiaoqi Acupuncture on the basis of the control group,both groups were treated for 14 consecutive days.After 2 weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes of white blood cell count(WBC),C-reactive protein(CRP)and clinical pulmonary infection score(CPIS)were observed before and after treatment.The changes of diaphragmatic activity were compared before and after treatment between the two groups.Results(1)After treatment,the WBC and CRP levels of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving the WBC and CRP levels,with statistically significant differences(P＜0.05).(2)After treatment,the CPIS scores of patients in the two groups were significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving CPIS scores,with a statistically significant difference(P＜0.05).(3)After treatment,the diaphragm mobility of patients in the two groups was significantly improved(P＜0.05),and the observation group was significantly superior to the control group in improving diaphragm mobility,and the difference was statistically significant(P＜0.05).(4)The total effective rate was 91.67％(33/36)in the observation group and 75.00％(27/36)in the control group.The efficacy of the observation group was superior to that of the control group,and the difference was statistically significant(P＜0.05).Conclusion Sanjiao Tiaoqi Acupuncture for post-stroke respiratory dysfunction can significantly promote the absorption of inflammatory factors in patients and improve diaphragm mobility,with remarkable clinical efficacy.

In the treatment of persistent atrial fibrillation with radiofrequency ablation,it is often necessary to add the ablation of external trigger foci of pulmonary vein on the basis of annular pulmonary vein isolation,including linear ablation,BOX ablation and fragmentation potential ablation.The isthmus of mitral valve is the most important component of linear ablation,but it is difficult to reach the isthmus of mitral valve for complete blockade by conventional radiofrequency ablation.The guide catheter was transported through the inferior vena cava to the coronary sinus,and the injection of Marshall vein anhydrous ethanol for ablation could achieve epicardial and myocardial block in the mitral isthmus,and the ablation combined with the endocardial patch ablation in the mitral isthmus could significantly improve the ablation effect,but there were disadvantages such as Marshall vein and coronary vein injury,high surgical cost and long time.This paper reports a case of persistent atrial fibrillation treated by self-made perforated balloon with Marshall intravenous anhydrous ethanol combined with individualized ablation strategy.No major adverse cardiovascular events or recurrence of atrial fibrillation occurred during 6 months of follow-up after discharge.