Insulin-like growth factor 2 (IGF2) is a critical endocrine mediator implicated in male reproductive physiology. To investigate the correlation between IGF2 protein levels and various aspects of male infertility, specifically focusing on sperm quality, inflammation, and DNA damage, a cohort of 320 male participants was recruited from the Women's Hospital, Zhejiang University School of Medicine (Hangzhou, China) between 1 st January 2024 and 1 st March 2024. The relationship between IGF2 protein concentrations and sperm parameters was assessed, and Spearman correlation and linear regression analysis were employed to evaluate the independent associations between IGF2 protein levels and risk factors for infertility. Enzyme-linked immunosorbent assay (ELISA) was used to measure IGF2 protein levels in seminal plasma, alongside markers of inflammation (tumor necrosis factor-alpha [TNF-α] and interleukin-1β [IL-1β]). The relationship between seminal plasma IGF2 protein levels and DNA damage marker phosphorylated histone H2AX (γ-H2AX) was also explored. Our findings reveal that IGF2 protein expression decreased notably in patients with asthenospermia and teratospermia. Correlation analysis revealed nuanced associations between IGF2 protein levels and specific sperm parameters, and low IGF2 protein concentrations correlated with increased inflammation and DNA damage in sperm. The observed correlations between IGF2 protein levels and specific sperm parameters, along with its connection to inflammation and DNA damage, underscore the importance of IGF2 in the broader context of male reproductive health. These findings lay the groundwork for future research and potential therapeutic interventions targeting IGF2-related pathways to enhance male fertility.
Humans ; Male ; Insulin-Like Growth Factor II/metabolism* ; Infertility, Male/genetics* ; DNA Damage ; Adult ; Inflammation/metabolism* ; Spermatozoa/metabolism* ; Semen Analysis ; Semen/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Histones/metabolism* ; Interleukin-1beta/metabolism*

OBJECTIVE: To investigate the effects of acupuncture on the neurotransmitter levels and gut microbiota in a mouse model of Tourette syndrome (TS). METHODS: Thirty-six male C57/BL6 mice were randomly divided into 4 groups using a random number table method: 3,3'-iminodipropionitrile (IDPN) group, control group, acupuncture group, and tiapride group, with 9 mice in each group. In the IDPN group, acupuncture group, and tiapride group, mice received daily intraperitoneal injections of IDPN (300 mg/kg body weight) for 7 consecutive days to induce stereotyped behaviors. Subsequently, in the acupuncture intervention group, standardized acupuncture treatment was administered for 14 consecutive days to IDPN-induced TS model mice. The selected acupoints included Baihui (DU 20), Yintang (DU 29), Waiguan (SJ 5), and Zulinqi (GB 41). In the tiapride group, mice were administered tiapride (50 mg/kg body weight) via oral gavage daily for 14 consecutive days. The control group, IDPN group, and acupuncture group received the same volume of saline orally for 14 consecutive days. Stereotypic behaviors were quantified through behavioral assessments. Neurotransmitter levels, including dopamine (DA), glutamate (Glu), and aspartate (ASP) in striatal tissue were measured using enzyme-linked immunosorbent assay. Dopamine transporter (DAT) expression levels were additionally quantified through quantitative polymerase chain reaction (qPCR). Gut microbial composition was analyzed through 16S ribosomal RNA gene sequencing, while metabolic profiling was conducted using liquid chromatography-mass spectrometry (LC-MS). RESULTS: Acupuncture administration significantly attenuated stereotypic behaviors, concurrently reducing striatal levels of DA, Glu and ASP concentrations while upregulating DAT expression compared with untreated TS controls (P<0.05 or P<0.01). Comparative analysis identified significant differences in Muribaculaceae (P=0.001), Oscillospiraceae (P=0.049), Desulfovibrionaceae (P=0.001), and Marinifilaceae (P=0.014) following acupuncture intervention. Metabolomic profiling revealed alterations in 7 metabolites and 18 metabolic pathways when compared to the TS mice, which involved various amino acid metabolisms associated with DA, Glu, and ASP. CONCLUSIONS Acupuncture demonstrates significant modulatory effects on both central neurotransmitter systems and gut microbial ecology, thereby highlighting its dual therapeutic potential for TS management through gut-brain axis regulation.
Animals ; Tourette Syndrome/metabolism* ; Gastrointestinal Microbiome ; Neurotransmitter Agents/metabolism* ; Acupuncture Therapy ; Male ; Mice, Inbred C57BL ; Mice

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Endodontic diseases are a kind of chronic infectious oral disease.Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha.However,it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy(RCT).Recent research,encompassing bacterial etiology and advanced imaging techniques,contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT.Success in RCT hinges on factors like patients,infection severity,root canal anatomy,and treatment techniques.Therefore,improving disease management is a key issue to combat endodontic diseases and cure periapical lesions.The clinical difficulty assessment system of RCT is established based on patient conditions,tooth conditions,root canal configuration,and root canal needing retreatment,and emphasizes pre-treatment risk assessment for optimal outcomes.The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT.These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

A domestically produced self-expanding transcatheter aortic valve controllable bending delivery system(VitaFlow? Ⅲcontrollable bending retrievable delivery system)was first used to perform transcatheter aortic valve replacement(TAVR)in a symptomatic severe aortic valve stenosis patient with severe heart failure and high risk of surgery in China on September 22,2023.The patient successfully completed TAVR under general anesthesia,with good valve position and function after the operation.Before discharge and at one month of follow-up,the patient's symptoms and degree of heart failure were significantly improved.The follow-up results of this case showed that the VitaFlow? Ⅲ controllable bending retrievable delivery system for TAVR is safe and feasible,and future prospective,multicenter clinical trials are expected to evaluate its efficacy.

Objective To evaluate the efficacy of surgery,chemotherapy and surgery combined chemotherapy for retinoblastoma(RB),and analyze the prognostic factors of RB patients.Methods Clinical data of 1188 RB patients registered in the Surveillance,Epidemiology and End Results(SEER)database from January 2000 to December 2019 were retrospectively analyzed.The baseline characteristics of patients treated with surgery,chemotherapy or surgery combined with chemotherapy were balanced by inverse probability of treatment weighting(IPTW).Log-rank test analysis was used to compare the survival probability of patients in the 3 groups,and Cox regression models were used to analyse the factors influencing the prognosis of RB patients.Results A total of 1188 RB cases were included in this study,including 426 cases in surgery group,200 cases in chemotherapy group and 562 cases in surgery combined with chemotherapy group.After IPTW weighting,baseline data such as age,sex and race were balanced(P＞0.05).Log-rank test results showed that the survival curves of the three groups were significantly different before and after weighting(P＜0.05).After weighted,the survival of patients in surgery group was significantly better than that in chemotherapy group and surgery combined chemotherapy group(P＜0.05),and there was no statistical significance between chemotherapy group and surgery combined chemotherapy group(P＞0.05).The weighted patient survival probability at 1st,3rd and 5th years were 99.7%,98.9%and 98.6%in surgery group;97.4%,95.8%and 95.8%in chemotherapy group;and 97.9%,95.8%and 95.0%in surgery combined chemotherapy group.Cox regression analysis showed that compared with surgery group,the specific risk ratio of death was 1.367(95%CI 1.100-1.700)in chemotherapy group and 1.132(95%CI 0.963-1.330)in combined chemotherapy group.Compared with patients with 1 RB lesion,the patient-specific mortality risk ratio for patients with 2 or more RB lesions was 0.399(95%CI 0.268-0.594).Conclusions Patients with RB have higher survival rates probability after treatment.After controlling the influence of age,sex and other factors,the effect of surgery was better among the three treatment methods.Multifocality may be an independent prognostic factor in RB patients.

OBJECTIVE: To explore the effectiveness of manipulation treatment for lumbar disc herniation (LDH) based on the model of muscle and bone assessment. METHODS: From May 2022 to August 2023, using the methods single-center randomized controlled in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 72 patients were treated with LDH and divided into muscle and bone assessment model manipulation group and the two step seven gimmick group according to the random number table method, the muscle and bone assessment model manipulation group fall off in 1 case, the two step seven gimmick group falls off in 2 cases. There were 35 cases in the muscle and bone assessment model manipulation group, including 12 males and 23 females;The age was 27 to 48 years old with an average of (37.77±7.63) years old. The course of disease was 35 to 180 days with an average of (83.68±69.01) days. The patients were treated with manual therapy under the guidance of muscle and bone assessment model, twice a week for 4 weeks. There were 34 cases in the two step seven gimmick group including 12 males and 22 females;The age was 26 to 49 years old with an average of (37.59±7.43) years old;The course of disease was 40 to 175 days with an average of (82.15±68.87) days. The patients were treated with two step seven gimmick method, 2 times a week, for 4 weeks. The visual analogue scale (VAS) and Oswestry disability index (Oswestry disability index, ODI) questionnaire, muscle tension and lumbar spine angle and the straight leg-raising activities were compared between two groups before and 4 weeks after treatment. RESULTS: The VAS of the muscle and bone assessment model manipulation group and the two step seven gimmick group(6.51±0.61) and (6.62±0.56) before treatment decreased to 2.40±0.81 and 3.18±0.78 after 4 weeks of treatment, respectively, and the muscle and bone assessment model manipulation group was significantly lower than the two step seven gimmick group (P<0.01). The ODI of the muscle and bone assessment model manipulation group and the two step seven gimmick group were (64.57±5.11) and (65.02±5.18) before treatment, decreased to (18.60±2.27) and (24.70±2.14) after 4 weeks of treatment, and the ODI of the muscle and bone assessment model manipulation group was significantly lower than that of the two step seven gimmick group (P<0.01). Before the treatment, side erector spinae, gluteus medius, and gastrocnemius muscle tension were (59.95±2.60), (62.59±2.51), (49.97±2.01) in the muscle and bone assessment model manipulation group and (60.39±3.84), (62.47±3.27), (49.55±1.27) in the two step seven gimmick group;After 4 weeks of treatment, the muscle tension of erector spinae, gluteus medius and gastrocnemius on the affected side were (56.58±2.71), (60.44±2.31) and (49.19±1.57) in the muscle and bone assessment model manipulation group, (58.28±3.79), (60.11±2.87), (48.55±0.90) in the two step seven gimmick group, the differences had statistical significance before and after treatment of two groups(P<0.01). The muscle and bone assessment model manipulation group was better than the two step seven gimmick group in improving the erector spinae muscle tension on the affected side (P<0.05), and there was no significant difference in the rest (P>0.05). Before the treatment, lumbar proneness, stretch, subject to lateral flexion and lateral angle of the straight leg-raising on the affected side were (46.00±8.89)°, (13.57±3.75)°, (12.29±3.50) °, (43.71±7.98) ° in the muscle and bone assessment model manipulation group, (45.14±6.24) °, (12.23±3.75) °, (12.66±2.98) ° and (44.18±3.50) ° in the two step seven gimmick group. After 4 weeks of treatment, the angles of lumbar flexion, extension, flexion on the affected side and straight leg raising on the affected side were (76.29±4.43) °, (20.00±1.71) °, (22.43±2.81) °, (70.41±7.59) ° in the muscle and bone assessment model manipulation group, and (75.75±6.38) °, (16.43±3.36) °, (20.19±3.52) °, (65.42±6.15) ° in the two step seven gimmick group. The difference had statistical significance before and after treatment in two groups(P<0.01), a comparison between groups, after 4 weeks of treatment, the angles of lumbar flexion and extension, affected side flexion, and lower limb straight leg elevation in the muscle and bone assessment model manipulation group were better than those in the two step seven gimmick group (P<0.05). Before the treatment, pelvic tilt, lumbar lordosis angle were (2.71±1.01) mm, (37.63±3.35) ° in the muscle and bone assessment model manipulation group, and (2.69±0.97) mm, (36.98±3.73) ° in the two step seven gimmick group;After 4 weeks of treatment, the pelvic tilt and lumbar lordosis angle were (0.84±0.36) mm and (41.64±2.96) ° in the muscle and bone assessment model manipulation group, and those in the method of two step seven gimmick group were (1.18±0.75) mm and (41.70±3.14) °. There were significant differences before and after treatment in both groups (P<0.01), and the improvement of pelvic tilt in the muscle and bone assessment model manipulation group was better than that in the method of two step seven gimmick group after 4 weeks of treatment (P<0.05). CONCLUSION The manipulation under the guidance of the muscle and bone assessment model can effectively improve the pain and dysfunction of LDH patients, and has a better effect than the two-step seven-method manipulation group in improving the muscle tension, lumbar motion function and posture.
Humans ; Male ; Female ; Intervertebral Disc Displacement/physiopathology* ; Middle Aged ; Adult ; Lumbar Vertebrae

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.
Humans ; Mesothelioma, Malignant ; Mesothelioma/diagnosis* ; Lung Neoplasms/genetics* ; Pleural Neoplasms/diagnosis* ; Prognosis ; Biomarkers, Tumor/analysis* ; Extracellular Matrix Proteins ; CD24 Antigen/genetics*

Humans ; Epstein-Barr Virus Infections ; Immune Checkpoint Inhibitors ; Herpesvirus 4, Human

Morphine is a frequently used analgesic that activates the mu-opioid receptor(MOR),which has prominent side effects of tolerance.Although the inefficiency of morphine in inducing the endocytosis of MOR underlies the development of morphine tolerance,currently,there is no effective therapy to treat morphine tolerance.In the current study,we aimed to develop a monoclonal antibody(mAb)precisely targeting MOR and to determine its therapeutic efficacy on morphine tolerance and the underlying molecular mechanisms.We successfully prepared a mAb targeting MOR,named 3A5C7,by hybridoma technique using a strategy of deoxyribonucleic acid immunization combined with cell immunization,and identified it as an immunoglobulin G mAb with high specificity and affinity for MOR and binding ability to antigens with spatial conformation.Treatment of two cell lines,HEK293T and SH-SY5Y,with 3A5C7 enhanced morphine-induced MOR endocytosis via a G protein-coupled receptor kinase 2(GRK2)/β-arrestin2-dependent mechanism,as demonstrated by immunofluorescence staining,flow cytometry,Western blotting,coimmunoprecipitation,and small interfering ribonucleic acid(siRNA)-based knock-down.This mAb also allowed MOR recycling from cytoplasm to plasma membrane and attenuated morphine-induced phosphorylation of MOR.We established an in vitro morphine tolerance model using differentiated SH-SY5Y cells induced by retinoic acid.Western blot,enzyme-linked immunosorbent assays,and siRNA-based knockdown revealed that 3A5C7 mAb diminished hyperactivation of adenylate cyclase,the in vitro biomarker of morphine tolerance,via the GRK2/β-arrestin2 pathway.Furthermore,in vivo hotplate test demonstrated that chronic intrathecal administration of 3A5C7 significantly alle-viated morphine tolerance in mice,and withdrawal jumping test revealed that both chronic and acute 3A5C7 intrathecal administration attenuated morphine dependence.Finally,intrathecal electroporation of silencing short hairpin RNA illustrated that the in vivo anti-tolerance and anti-dependence efficacy of 3A5C7 was mediated by enhanced morphine-induced MOR endocytosis via GRK2/β-arrestin2 pathway.Collectively,our study provided a therapeutic mAb,3A5C7,targeting MOR to treat morphine tolerance,mediated by enhancing morphine-induced MOR endocytosis.The mAb 3A5C7 demonstrates promising translational value to treat clinical morphine tolerance.