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 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.

Primary hypertrophic osteoarthropathy(PHO)is a rare disease also known as pachydermo-periostosis.We reported a painless case whose diagnosis was confirmed by genetic test.A 24-year-old male presented a series of symptoms that first began at 14.He suffered from progressive clubbed-fingers accompa-nied by swelling of the wrist and ankle joints.Facial skin concentric thickening and alar nose broadening ap-peared simultaneously and increased progressively.He was also prone to acne and hyperhidrosis.X-rays showed thickening of the metacarpal and phalangeal bones,as well as symmetrical periosteal ossification of both the tibia and fibula.Clinical diagnosis of PHO is difficult because of the variable features.With acromeg-aly excluded,the diagnosis was confirmed by a genetic test.Whole exome sequencing revealed a heterozygous SLCO2A1 c.611C＞T(p.Ser204Lue)and SLCO2A1 c.1602C＞A(p.Asn534Lys)mutation from each par-ent.It suggests that primary hypertrophic osteoarthropathy should be considered for young limb hypertrophic patients especially when periosteal thickening signs were showed in X-ray.A confirmatory diagnosis can be made through the genetic test.

Objective Postoperative delirium(POD)has become a critical challenge with severe consequences and increased incidences as the global population ages.However,the underlying mechanism is yet unknown.Our study aimed to explore the changes in metabolites in three specific brain regions and saliva of older mice with postoperative delirium behavior and to identify potential non-invasive biomarkers. Methods Eighteen-month-old male C57/BL6 mice were randomly assigned to the anesthesia/surgery or control group.Behavioral tests were conducted 24 h before surgery and 6,9,and 24 h after surgery.Complement C3(C3)and S100 calcium-binding protein B protein(S100beta)levels were measured in the hippocampus,and a metabolomics analysis was performed on saliva,hippocampus,cortex,and amygdala samples. Results In total,43,33,38,and 14 differential metabolites were detected in the saliva,hippocampus,cortex,and amygdala,respectively."Pyruvate""alpha-linolenic acid"and"2-oleoyl-1-palmitoy-sn-glycero-3-phosphocholine"are enriched in one common pathway and may be potential non-invasive biomarkers for POD.Common changes were observed in the three brain regions,with the upregulation of 1-methylhistidine and downregulation of D-glutamine. Conclusion Dysfunctions in energy metabolism,oxidative stress,and neurotransmitter dysregulation are implicated in the development of POD.The identification of changes in the level of salivary metabolite biomarkers could aid in the development of noninvasive diagnostic methods for POD.

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.