As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Persistent infection with high-risk human papillomavirus(HR-HPV) is the primary etiological factor in cervical lesions and cervical cancer. Toll-like receptors(TLRs), as important pattern recognition receptors of the innate immune system, play a key role in the persistence of cervical HR-HPV infection. The "latent pathogen theory" in traditional Chinese medicine(TCM) holds that latent pathogens have both "latent" and "triggered" characteristics, which closely resemble the persistent infection and latent pathogenic potential of cervical HR-HPV. Guided by the "latent pathogen theory" and using contemporary immunological techniques, this paper explores the bidirectional immunomodulatory effects of TLRs in the persistence of cervical HR-HPV infection and their relationship with latent pathogens. The results indicate that TLRs play a crucial role in immune recognition and modulation. Dysregulation and overactivation of TLRs can induce chronic inflammation, allowing cervical HR-HPV to persist and evade immune detection. TLR dysfunction, coupled with a deficiency in healthy Qi that prevents the expulsion of pathogens, is a critical factor in the pathogenicity of latent pathogens. Restoring healthy Qi to modulate the immune functions of TLRs emerges as an important strategy for clearing cervical HR-HPV infection. By harmonizing the spleen and kidney and regulating immune balance, it is possible to reverse cervical HR-HPV infection, providing a scientific basis for clinical research.
Humans ; Toll-Like Receptors/genetics* ; Female ; Papillomavirus Infections/genetics* ; Papillomaviridae/immunology* ; Persistent Infection/genetics* ; Uterine Cervical Neoplasms/immunology* ; Animals ; Medicine, Chinese Traditional ; Cervix Uteri/immunology* ; Human Papillomavirus Viruses

OBJECTIVE: To investigate the genetic causal relationship of leukocyte telomere length (LTL) with prostatitis, orchitis and epididymitis by two-sample Mendelian randomization (MR). METHODS: Using LTL as the exposure factor and prostatitis, orchitis and epididymitis as outcome factors, we mined the Database of Genome-Wide Association Studies (GWAS). Then, we analyzed the causal relationship of LTL with prostatitis, orchitis and epididymitis by Mendelian randomization using inverse variance weighting (IVW) as the main method and weighted median and MR-Egger regression as auxiliary methods, determined the horizontal multiplicity by MR-Egger intercept test, and conducted sensitivity analysis using the leaving-one-out method. RESULTS: A total of 121 related single nucleotide polymorphisms (SNPs) were identified in this study. IVW showed LTL to be a risk factor for prostatitis (OR = 1.383, 95% CI: 1.044－1.832, P = 0.024), and for orchitis and epididymitis as well (OR = 1.770, 95% CI: 1.275－2.456, P = 0.000 6). CONCLUSION Genetic evidence from Mendelian randomized analysis indicates that shortening of LTL reduces the risk of prostatitis, orchitis and epididymitis.
Humans ; Male ; Mendelian Randomization Analysis ; Epididymitis/genetics* ; Prostatitis/genetics* ; Polymorphism, Single Nucleotide ; Leukocytes ; Orchitis/genetics* ; Genome-Wide Association Study ; Telomere ; Risk Factors

Objective To investigate the mechanism by which suppressor of cytokine signaling 3(SOCS3)regulates microglial inflammation through nuclear factor-kappaB(NF-κB),providing novel mechanistic insights into microglial involvement in Parkinson's disease(PD)pathogenesis.Methods ① Ten male C57BL/6 mice(12 weeks old,weighing 20～25 g)were subjected to intraperitoneal injection of 15 mg/kg MPTP to establish a PD model.Rotarod test was used to assess motor function.Western blotting was employed to detect the protein expression of tyrosine hydroxylase(TH)and ionized calcium-binding adapter molecule 1(IBA-1)in the substantia nigra.RT-qPCR was utilized to measure the mRNA level of SOCS3 in the substantia nigra.Immunohistochemistry was performed to assess NF-κB p65 subunit expression.The expression of SOCS3,NF-κB and p-NF-κB was measured with Western blotting.② Microglial cell line BV2 was stimulated with 1 000 ng/mL lipopolysaccharide(LPS)for 6 h to establish an inflammatory model.Subsequently,SOCS3 was knocked down.NF-κB inhibitor BAY 11-7082 was used to treat the cells.RT-qPCR and Western blotting were used to measure the expression of SOCS3 at mRNA and protein levels.Western blotting was also applied to detect the expression of NF-κB and p-NF-κB,and ELISA was conducted to measure TNF-α and IL-1β levels in the culture supernatant.Immunofluorescence assay was carried out to localize NF-κB(nuclear vs cytoplasmic).③ A co-culture system of BV2 microglia and N2a neuroblastoma cells was established to investigate the regulatory effects of microglia on neuronal cells.MTT assay and TUNEL staining were used respectively to determine cell viability and apoptosis of N2a cells.Results ① Compared to the control mice,the PD mouse model exhibited reduced rotarod fall latency,down-regulation in TH and SOCS3(P<0.01),up-regulation in IBA-1 and increased p-NF-κB/NF-κB ratio(P<0.01).② In BV2 cells,LPS stimulation increased TNF-α,IL-1β,and p-NF-κB/NF-κB ratio(P<0.01),while down-regulated SOCS3 expression(P<0.01).SOCS3 knockdown in LPS-stimulated BV2 cells further increased the p-NF-κB/NF-κB ratio(P<0.01),increased nuclear localization of NF-κB,and elevated TNF-α and IL-1β levels(P<0.01).BAY 11-7082 treatment in these SOCS3-knockdown,LPS-stimulated cells resulted in reduced p-NF-κB/NF-κB ratio,TNF-α,and IL-1β(P<0.01),and decreased NF-κB nuclear distribution.③ LPS-stimulated BV2 cells reduced cell viability and increased cell apoptosis in N2a cells(P<0.01).SOCS3 knockdown in BV2 cells exacerbated the reduction in N2a cell viability(P<0.01)and the increase in cell apoptosis in N2a cells(P<0.01).BAY 11-7082 treatment of these SOCS3-knockdown BV2 microglia attenuated the reduction in N2a cell viability and decreased apoptosis in N2a cells(P<0.01).Conclusion SOCS3 inhibits microglia inflammatory response through down-regulation of NF-kB activity,and in turn attenuates neuronal cell death and ameliorates PD nerve injury.

Objective To demonstrate that neferine(Nef)alleviates Parkinson's disease(PD)by inhibiting microglial pyroptosis mediated through the reactive oxygen species(ROS)/NOD-like receptor protein 3(NLRP3)/Caspase-1 pathway.Methods BV2 microglial cells were divided into:control group,lipopolysaccharides(LPS)-adenosine triphosphate(ATP)group,and LPS-ATP+Nef group.Pyroptosis was induced by 1 μg/mL LPS+5 mmol/L ATP,with 2 mmol/L Nef pretreatment.Eighteen 10-12-week-old male C57BL/6 mice(22～25 g)were randomly assigned to:control(n=6),1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)(n=6),and MPTP+Nef(n=6)groups.Detection methods included:flow cytometry for pyroptosis,Cell Counting Kit-8(CCK-8)for viability,2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)for ROS,commercial kits for malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH),ELISA/Western blot for interleukin-1β(IL-1β)/IL-18,immunofluorescence/immunohistochemistry for NLRP3/Caspase-1,tyrosine hydroxylase(TH)immunohistochemistry,hematoxylin-eosin staining for neuropathology,and modified neurological severity score(mNSS).Results Versus control,LPS-ATP group showed decreased viability(P=0.002),increased pyroptosis(P<0.001),elevated ROS(P<0.001)/MDA(P<0.001)/IL-1β(P<0.001)/IL-18(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001),and reduced GSH(P<0.001)/SOD(P<0.001).Nef treatment reversed these effects(all P<0.05).According to the results of murine studies,compared with the control group,the MPTP group had increased mNSS(P<0.001)/tissue ROS(P<0.001),downregulated TH(P<0.001),upregulated NLRP3(P<0.001)/Caspase-1(P<0.001).Nef treatment significantly attenuated the MPTP-induced deleterious effects(P<0.05).Histopathological analysis revealed that control group exhibited uniformly distributed hippocampal neurons with distinct nuclear morphology;MPTP group showed neuronal swelling,interstitial edema,and nuclear atrophy;MPTP+Nef group demonstrated ameliorated neuronal damage.Conclusion Nef inhibits microglial pyroptosis via ROS/NLRP3/Caspase-1 axis,ameliorating PD neuroinflammation and pathology.

Objective: To explore the relationship between parenting style and emotional behavior problems in children with development dyslexia (DD), so as to provide reference for family support and intervention measures. Methods: From June to September 2023, 201 children in DD group and typically developing matched by age and sex were selected from the students in grades 3-6 of 4 primary schools in a district of Xinjiang by random cluster sampling method. The Childrens Version of the Parenting Style Scale and the Strength and Difficulty Scale were administered, and the occurrence of childrens emotional behavior problems and parentingstyles in the two groups were compared by Chisquare test and Wicoxon rank sum test. The correlation between parents parenting styles and childrens emotional behavior problems was analyzed by generalized linear regression. Results: The detection rates of emotional behavior problems were 45.77% in DD group and 15.42% in normal control children group. The differences in parenting styles between fathers and mothers of the DD group and the normal control group were statistically significant in terms of emotional warmth, parenting anxiety, and overprotection (Z=4.02, 29.03; 4.94, 26.32; 23.47, 5.30, P<0.05). Generalized linear regression analysis showed that father affective warmth was positively correlated with emotional symptoms, hyperactivity, peer interaction problems and prosocial behaviors (β=0.08, 0.05, 0.05, 0.09, P<0.05). The emotional warmth of mothers in DD group was negatively correlated with emotional symptoms, conduct problems, hyperactivity and peer interaction problems (β=-0.18, -0.08, -0.07, -0.08, P<0.05). Conclusions Parenting style is an important factor affecting the emotional behavior problems of DD children. Improving parenting style can reduce the occurrence of emotional behavior problems of DD children.

Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of fetal growth re-striction(FGR)with varying severity and provide guidance for clinical counseling and management of FGR.Meth-ods:A total of 141 pregnant women with FGR treated at Sichuan Maternal and Child Health Hospital from January 2020 to June 2021 were selected for the retrospective study.They were divided into the mild FGR group(3th≤EFW＜10th,84 cases)and the severe FGR group(EFW＜3th,57 cases)based on different estimated fetal weight(EFW).All pregnant women underwent amniocentesis for prenatal diagnosis.The chromosome results and preg-nancy outcomes of the two groups were statistically analyzed.Results:19 cases(13.5%)of 141 fetuses with FGR were found with chromosome abnormalities.The rate of chromosomal abnormalities was 19.3%(11/57)in the severe FGR group,which was higher than the 9.5%(8/84)in the mild FGR group,but the difference was not statistically significant(P=0.095).110 cases underwent both karyotype analysis and chromosome microarray a-nalysis(CMA).The detection rate of chromosomal abnormalities in CMA was 13.6%,which was significantly higher than 4.5%in karyotype analysis(P=0.006).Among chromosomal abnormalities,chromosomal aneu-ploidy accounted for 21.05%(4/19),including 1 case of trisomy 18 and 2 cases of 47,XXY.Two cases with dele-tion in the 4p16.3 regions were found in the severe FGR group,and these deletions are associated with Wolf-Hir-schhorn syndrome.The termination rate of pregnancy and admission to the neonatal intensive care unit in the se-vere FGR group were higher than those in the mild FGR group.In contrast,the full-term delivery rate and newborn birth weight were lower in the severe FGR group compared to the mild FGR group,showing statistically significant differences(P＜0.05).There was no statistically significant difference in the rates of stillbirth and preterm birth be-tween the two groups(P＞0.05).Conclusions:The detection rate of chromosomal abnormalities using CMA in fetuses with FGR was higher than traditional karyotyping.Therefore,it is recommended to combine karyotyping with CMA for invasive prenatal diagnosis of FGR fetuses.The risk of adverse pregnancy outcomes increases with severe FGR,and monitoring should be intensified during pregnancy and the perinatal period to reduce adverse pregnancy outcomes.

Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of fetal growth re-striction(FGR)with varying severity and provide guidance for clinical counseling and management of FGR.Meth-ods:A total of 141 pregnant women with FGR treated at Sichuan Maternal and Child Health Hospital from January 2020 to June 2021 were selected for the retrospective study.They were divided into the mild FGR group(3th≤EFW＜10th,84 cases)and the severe FGR group(EFW＜3th,57 cases)based on different estimated fetal weight(EFW).All pregnant women underwent amniocentesis for prenatal diagnosis.The chromosome results and preg-nancy outcomes of the two groups were statistically analyzed.Results:19 cases(13.5%)of 141 fetuses with FGR were found with chromosome abnormalities.The rate of chromosomal abnormalities was 19.3%(11/57)in the severe FGR group,which was higher than the 9.5%(8/84)in the mild FGR group,but the difference was not statistically significant(P=0.095).110 cases underwent both karyotype analysis and chromosome microarray a-nalysis(CMA).The detection rate of chromosomal abnormalities in CMA was 13.6%,which was significantly higher than 4.5%in karyotype analysis(P=0.006).Among chromosomal abnormalities,chromosomal aneu-ploidy accounted for 21.05%(4/19),including 1 case of trisomy 18 and 2 cases of 47,XXY.Two cases with dele-tion in the 4p16.3 regions were found in the severe FGR group,and these deletions are associated with Wolf-Hir-schhorn syndrome.The termination rate of pregnancy and admission to the neonatal intensive care unit in the se-vere FGR group were higher than those in the mild FGR group.In contrast,the full-term delivery rate and newborn birth weight were lower in the severe FGR group compared to the mild FGR group,showing statistically significant differences(P＜0.05).There was no statistically significant difference in the rates of stillbirth and preterm birth be-tween the two groups(P＞0.05).Conclusions:The detection rate of chromosomal abnormalities using CMA in fetuses with FGR was higher than traditional karyotyping.Therefore,it is recommended to combine karyotyping with CMA for invasive prenatal diagnosis of FGR fetuses.The risk of adverse pregnancy outcomes increases with severe FGR,and monitoring should be intensified during pregnancy and the perinatal period to reduce adverse pregnancy outcomes.

Objective:To analyze the prenatal diagnosis results and pregnancy outcomes of fetal growth re-striction(FGR)with varying severity and provide guidance for clinical counseling and management of FGR.Meth-ods:A total of 141 pregnant women with FGR treated at Sichuan Maternal and Child Health Hospital from January 2020 to June 2021 were selected for the retrospective study.They were divided into the mild FGR group(3th≤EFW＜10th,84 cases)and the severe FGR group(EFW＜3th,57 cases)based on different estimated fetal weight(EFW).All pregnant women underwent amniocentesis for prenatal diagnosis.The chromosome results and preg-nancy outcomes of the two groups were statistically analyzed.Results:19 cases(13.5%)of 141 fetuses with FGR were found with chromosome abnormalities.The rate of chromosomal abnormalities was 19.3%(11/57)in the severe FGR group,which was higher than the 9.5%(8/84)in the mild FGR group,but the difference was not statistically significant(P=0.095).110 cases underwent both karyotype analysis and chromosome microarray a-nalysis(CMA).The detection rate of chromosomal abnormalities in CMA was 13.6%,which was significantly higher than 4.5%in karyotype analysis(P=0.006).Among chromosomal abnormalities,chromosomal aneu-ploidy accounted for 21.05%(4/19),including 1 case of trisomy 18 and 2 cases of 47,XXY.Two cases with dele-tion in the 4p16.3 regions were found in the severe FGR group,and these deletions are associated with Wolf-Hir-schhorn syndrome.The termination rate of pregnancy and admission to the neonatal intensive care unit in the se-vere FGR group were higher than those in the mild FGR group.In contrast,the full-term delivery rate and newborn birth weight were lower in the severe FGR group compared to the mild FGR group,showing statistically significant differences(P＜0.05).There was no statistically significant difference in the rates of stillbirth and preterm birth be-tween the two groups(P＞0.05).Conclusions:The detection rate of chromosomal abnormalities using CMA in fetuses with FGR was higher than traditional karyotyping.Therefore,it is recommended to combine karyotyping with CMA for invasive prenatal diagnosis of FGR fetuses.The risk of adverse pregnancy outcomes increases with severe FGR,and monitoring should be intensified during pregnancy and the perinatal period to reduce adverse pregnancy outcomes.