This study primarily aimed to investigate the prevalence of human papillomavirus (HPV) and other common pathogens of sexually transmitted infections (STIs) in spermatozoa of infertile men and their effects on semen parameters. These pathogens included Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae, Pseudomonas aeruginosa , and Staphylococcus aureus . A total of 1951 men of infertile couples were recruited between 23 March 2023, and 17 May 2023, at the Department of Reproductive Medicine of The First People's Hospital of Yunnan Province (Kunming, China). Multiplex polymerase chain reaction and capillary electrophoresis were used for HPV genotyping. Polymerase chain reaction and electrophoresis were also used to detect the presence of other STIs. The overall prevalence of HPV infection was 12.4%. The top five prevalent HPV subtypes were types 56, 52, 43, 16, and 53 among those tested positive for HPV. Other common infections with high prevalence rates were Ureaplasma urealyticum (28.3%), Ureaplasma parvum (20.4%), and Enterococcus faecalis (9.5%). The prevalence rates of HPV coinfection with Ureaplasma urealyticum, Ureaplasma parvum, Chlamydia trachomatis, Mycoplasma genitalium , herpes simplex virus 2, Neisseria gonorrhoeae, Enterococcus faecalis, Streptococcus agalactiae , and Staphylococcus aureus were 24.8%, 25.4%, 10.6%, 6.4%, 2.4%, 7.9%, 5.9%, 0.9%, and 1.3%, respectively. The semen volume and total sperm count were greatly decreased by HPV infection alone. Coinfection with HPV and Ureaplasma urealyticum significantly reduced sperm motility and viability. Our study shows that coinfection with STIs is highly prevalent in the semen of infertile men and that coinfection with pathogens can seriously affect semen parameters, emphasizing the necessity of semen screening for STIs.
Humans ; Male ; Infertility, Male/epidemiology* ; Coinfection/microbiology* ; Papillomavirus Infections/virology* ; Adult ; Sexually Transmitted Diseases/complications* ; China/epidemiology* ; Staphylococcus aureus/isolation & purification* ; Chlamydia trachomatis/isolation & purification* ; Prevalence ; Mycoplasma genitalium/isolation & purification* ; Ureaplasma urealyticum/isolation & purification* ; Neisseria gonorrhoeae/isolation & purification* ; Enterococcus faecalis/isolation & purification* ; Streptococcus agalactiae/isolation & purification* ; Herpesvirus 2, Human/genetics* ; Pseudomonas aeruginosa/isolation & purification* ; Semen/virology* ; Sperm Motility ; Spermatozoa/microbiology* ; Human Papillomavirus Viruses

Non-small cell lung cancer (NSCLC) ranks among the most lethal malignancies worldwide. The clinical application of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have successfully revolutionized the treatment paradigm for EGFR-mutant NSCLC, significantly prolonging progression-free survival and establishing EGFR-TKIs as the standard first-line therapy for advanced lung adenocarcinoma. However, acquired resistance remains a major obstacle to sustained clinical benefit, with mechanisms that are highly heterogeneous. A phenomenon of "oxidative stress compensation" is commonly observed in EGFR-TKIs-resistant cells, where in redox homeostasis, through the precise regulation of reactive oxygen species (ROS) generation and elimination, plays a pivotal role in maintaining the balance between tumor cell proliferation and apoptosis. This review aims to innovatively construct a theoretical framework describing how dynamic redox regulation influences resistance to third-generation EGFR-TKIs. It focuses on the multifaceted roles of ROS in both EGFR-dependent and EGFR-independent resistance mechanisms, and further explores therapeutic strategies that target ROS kinetic thresholds and antioxidant systems. These insights not only propose an innovative "metabolic checkpoint" regulatory pathway to overcome acquired resistance to third-generation EGFR-TKIs, but also lay a molecular foundation for developing the redox biomarker-based dynamic therapeutic decision-making systems, thereby facilitating a shift in NSCLC therapy from single-target inhibition toward multi-dimensional metabolic remodeling in the context of precision medicine.
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Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; ErbB Receptors/genetics* ; Drug Resistance, Neoplasm/drug effects* ; Lung Neoplasms/genetics* ; Oxidation-Reduction/drug effects* ; Homeostasis/drug effects* ; Protein Kinase Inhibitors/therapeutic use* ; Reactive Oxygen Species/metabolism* ; Animals

To establish and optimize a method for the detection of recombinant human midkine (rhMK) activity and verify its methodology, cell counting kit-8 (cck-8) method was used to measure the proliferation activity of rat knee chondrocytes. The specificity, accuracy, precision, linearity and robustness of the method were also verified in this study. The established method was proven to have good specificity because the buffer of rhMK and recombinant human interleukin-1 receptor antagonist have no obvious active effect; the recoveries of the samples with relative activities of 50%, 75%, 100%, 125%, 150% were in the range of 80.0% to 124.0% by statistical analysis, the relative standard deviations (RSD) of relative potency were all within 20%, the linear correlation coefficient, R² ≥ 0.98, suggesting that the accuracy, precision and linearity of the method were good; the robustness correlation coefficient, R² ≥ 0.92 and the ratio of maximum to minimum of sigmoidal dose-response were no less than 1.5, indicating that robustness of the methods was good. In conclusion, a bioactivity measurement method for rhMK was established and fully validated in this study and it provides a reliable method for the bioactivity analysis of rhMK routine samples during the development. This study was approved by the Animal Care and Use Committee of Shanghai Model Organisms Center, Inc. (approval number: 2019-0008-06).

Objective To investigate the levels of serum folate and vitamin B12(VB12)and their association with the level of neurodevelopment in preschool children with autism spectrum disorder(ASD).Methods A total of 324 ASD children aged 2-6 years and 318 healthy children aged 2-6 years were recruited.Serum levels of folate and VB12 were measured using chemiluminescent immunoassay.The Social Responsiveness Scale and the Childhood Autism Rating Scale were used to assess the core symptoms of ASD children,and the Gesell Developmental Schedule was employed to evaluate the level of neurodevelopment.Results The levels of serum folate and VB12 in ASD children were significantly lower than those in healthy children(P＜0.05).Serum folate levels in ASD children were positively correlated with gross and fine motor developmental quotients(P＜0.05),and serum VB12 levels were positively correlated with adaptive behavior,fine motor,and language developmental quotients(P＜0.05).In ASD children aged 2 to＜4 years,serum folate levels were positively correlated with developmental quotients in all domains(P＜0.05),and serum VB12 levels were positively correlated with language developmental quotient(P＜0.05).In male ASD children,serum VB12 levels were positively correlated with language and personal-social developmental quotients(P＜0.05).Conclusions Serum folate and VB12 levels in preschool ASD children are lower than those in healthy children and are associated with neurodevelopmental levels,especially in ASD children under 4 years of age.Therefore,maintaining normal serum folate and VB12 levels may be beneficial for the neurodevelopment of ASD children,especially in ASD children under 4 years of age.[Chinese Journal of Contemporary Pediatrics,2024,26(4):371-377]

Objective:To investigate the clinical characteristic and genetic variants of children with carnitine palmitoyltransferase 2(CPT2)deficiency.Methods:The clinical and genetic data of 6 children with CPT2 deficiency were retrospectively analyzed.The blood acylcarnitines and genetic variants were detected with tandem mass spectrometry and whole-exon gene sequencing,respectively.Results:There were 4 males and 2 females with a mean age of 32 months(15 d-9 years)at diagnosis.One case was asymptomatic and with normal laboratory test results,2 had delayed onset,and 3 were of infantile type.Three cases were diagnosed at neonatal screening,and 3 cases presented with clinical manifestations of fever,muscle weakness,and increased muscle enzymes.Five children presented with decreased free carnitine and elevated levels of palmitoyl and octadecenoyl carnitines.CPT2 gene variants were detected at 8 loci in 6 children(4 harboring biallelic mutations and 2 harboring single locus mutations),including 3 known variants(p.R631C,p.T589M,and p.D255G)and 5 newly reported variants(p.F352L,p.R498L,p.F434S,p.A515P,and c.153-2A>G).It was predicted by PolyPhen2 and SIFT software that c.153-2A>G and p.F352L were suspected pathogenic variants,while p.R498L,p.F434S and p.A515P were variants of unknown clinical significance.Conclusions:The clinical phenotypes of CPT2 deficiency are diverse.An early diagnosis can be facilitated by neonatal blood tandem mass spectrometry screening and genetic testing,and most patients have good prognosis after a timely diagnosis and treatment.

The plants of Rutaceae, with wide distribution in China, have a long history of medicinal use. They contain a wide variety of alkaloids, which include isoquinolines, quinolines, acridones, carbazoles, and indoles. Pharmacological studies have shown that most of these alkaloids have antitumor, anti-inflammatory, antiviral, antidiabetic and other activities. This article summarized 378 alkaloids isolated from plants of Rutaceae and their pharmacological effects, aiming to lay a basis for future drug development and sustainable utilization of plant resources.
Alkaloids/chemistry* ; Humans ; Rutaceae/chemistry* ; Animals ; Drugs, Chinese Herbal/chemistry* ; Anti-Inflammatory Agents/chemistry*

Objective:To investigate the application effect of virtual simulation combined with flipped classroom in experimental teaching of the nursing care of falls in the elderly.Methods:The 497 nursing undergraduates in the class of 2019 in Chongqing Medical University were selected as subjects and were then divided into control group (two classes with 251 students) and intervention group (two classes with 246 students). The students in the control group received traditional experimental teaching, and those in the intervention group received blended experimental teaching with virtual simulation combined with flipped classroom. At the end of the course, the use of virtual simulation platform was analyzed for the students in the intervention group, and a questionnaire survey and theoretical examination were used to compare the effect of experimental teaching between the two groups. SPSS 27.0 was used for the t-test and the chi-square test. Results:The frequency of use of the virtual simulation platform was (2.65±1.38) times per person in the intervention group, with an online learning time of 54.12-147.32 minutes. The questionnaire survey showed that compared with the control group, the intervention group had significantly higher scores of the achievement of teaching objectives and teaching satisfaction ( P<0.05). Compared with the control group after teaching, the intervention group had significantly higher scores of teaching promotion in terms of stimulating learning interest, cultivating self-learning ability, developing clinical thinking ability, improving innovation, and enhancing health education ability ( P<0.05). The intervention group had a significantly higher theoretical examination score than the control group [(79.38±5.09) vs. (77.88±4.97), P<0.05]. Conclusions:In the blended experimental teaching of the nursing care of falls in the elderly, virtual simulation combined with flipped classroom can help students master related knowledge and skills and cultivate their self-learning ability, clinical thinking ability, innovation ability, and health education ability.

The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

OBJECTIVE: To explore the disease spectrum for abnormal 3-hydroxyisovalerylcarnitine (C5OH) metabolism identified through newborn screening and clinical diagnosis patients and the key points for differential diagnosis so as to raise the awareness of pediatricians for such diseases. METHODS: Clinical data of 85 neonates with abnormal C5OH metabolism identified from February 2004 to January 2022 at Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were collected. Their clinical manifestations and results of tandem mass spectrometry (MS/MS), gas chromatography mass spectrometry (GC-MS) and genetic testing were retrospectively analyzed. RESULTS: Among the 85 cases, 46 (54.1%) were identified by neonate screening, whilst 39 (45.9%) were clinically diagnosed patients. Five diseases were diagnosed, including 28 cases with multiple carboxylase deficiency (MCD, 32.9%), 29 cases with 3-methylcrotonyl-coenzymeAcarboxylasedeficiency (MCCD, 34.1%), 4 cases with 3-methylglutaconic acid (3-MGA, 4.7%), 7 cases with 3-hydroxy-3-methylglutaric acid (3-HMG, 8.2%), and 17 cases with beta-ketothiolase deficiency (BKD, 20.0%). The disorders were characterized by sudden onset, anorexia, vomiting, diarrhea, abnormal breathing, consciousness disorder, spasm and developmental delay. CONCLUSION Among newborns with abnormal C5OH metabolism, MCCD is the most common disorder, which was followed by BKD and MCD. For patients with abnormal C5OH metabolism, MCD is the most common, followed by BKD and 3-HMG. C5OH related diseases have great heterogeneity. Combination of blood acylcarnitine levels, urinary organic acid levels and genetic testing based on clinical characteristics can help to attain the diagnosis.
Humans ; Infant, Newborn ; China ; Neonatal Screening ; Retrospective Studies ; Tandem Mass Spectrometry/methods*