Cancer stem cells (CSCs) are widely acknowledged as primary mediators to the initiation and progression of tumors. The association between microbial infection and cancer stemness has garnered considerable scholarly interest in recent years. Porphyromonas gingivalis (P. gingivalis) is increasingly considered to be closely related to the development of oral squamous cell carcinoma (OSCC). Nevertheless, the role of P. gingivalis in the stemness of OSCC cells remains uncertain. Herein, we showed that P. gingivalis was positively correlated with CSC markers expression in human OSCC specimens, promoted the stemness and tumorigenicity of OSCC cells, and enhanced tumor formation in nude mice. Mechanistically, P. gingivalis increased lipid synthesis in OSCC cells by upregulating the expression of stearoyl-CoA desaturase 1 (SCD1) expression, a key enzyme involved in lipid metabolism, which ultimately resulted in enhanced acquisition of stemness. Moreover, SCD1 suppression attenuated P. gingivalis-induced stemness of OSCC cells, including CSCs markers expression, sphere formation ability, chemoresistance, and tumor growth, in OSCC cells both in vitro and in vivo. Additionally, upregulation of SCD1 in P. gingivalis-infected OSCC cells was associated with the expression of KLF5, and that was modulated by P. gingivalis-activated NOD1 signaling. Taken together, these findings highlight the importance of SCD1-dependent lipid synthesis in P. gingivalis-induced stemness acquisition in OSCC cells, suggest that the NOD1/KLF5 axis may play a key role in regulating SCD1 expression and provide a molecular basis for targeting SCD1 as a new option for attenuating OSCC cells stemness.
Porphyromonas gingivalis/pathogenicity* ; Stearoyl-CoA Desaturase/metabolism* ; Humans ; Carcinoma, Squamous Cell/pathology* ; Mouth Neoplasms/metabolism* ; Animals ; Neoplastic Stem Cells/microbiology* ; Mice, Nude ; Mice ; Nod1 Signaling Adaptor Protein/metabolism* ; Kruppel-Like Transcription Factors/metabolism* ; Cell Line, Tumor

Objective:To investigate the characteristic distribution of vaginal microbiota in infertile women.Methods:We collected the results of vaginal microbiological examinations from 19322 initial visit infertile women who visited the Reproductive Medicine Center of the Department of Obstetrics and Gynecology,the Second Affili-ated Hospital of Air Force Medical University from March 1,2023 to July 31,2024.The vaginal microbiota infection status of patients was compared in different age groups(＜25 years old,25-＜30 years old,30-＜35 years old,35-＜40 years old,≥40 years old)and different seasons(spring,summer,autumn,winter).Results:①Among 19322 women,6027 cases(31.19％)showed abnormal vaginal microecology.Pathogenic microorganisms were detected in 3093 cases,including 2882 cases of single vaginitis,211 cases of mixed vaginitis,3764 cases with vagi-nal cleanliness grade Ⅲ-Ⅳ,and 3965 cases with abnormal lactobacilli.Among patients with single vaginitis,1349 cases(46.81％)were diagnosed with vulvovaginal candidiasis(VVC),which was the highest proportion.Aerobic vaginitis(AV)followed with 752 cases(26.09％),and bacterial vaginosis(BV)had 671 cases(23.28％),trichomonal vaginitis(TV)with 110 cases(3.82％).Among patients with mixed vaginitis,AV+BV was the most common with 96 cases(45.49％).②The detection rates of cleanliness grade Ⅲ-Ⅳ,abnormal lactobacilli,abnor-mal microorganisms(unclear pathogen),single vaginitis(BV,VVC and TV),and mixed vaginitis showed statisti-cally significant differences across different seasons(P＜0.05).Specifically,the detection rates of cleanliness grade Ⅲ-Ⅳ and abnormal microorganisms(unclear pathogens)were significantly higher in autumn than in other seasons(P＜0.05),while the detection rate of abnormal lactobacilli was higher in spring than in other seasons(P＜0.05).③The detection rates of abnormal lactobacilli,abnormal microorganisms(unclear pathogen),single vaginitis(BV,VVC and AV),and mixed vaginitis showed significant differences among different age groups(P＜0.05).Specifically,the detection rate of abnormal microorganisms(unclear pathogen)was higher in the age group＜25 years than in other age groups(P＜0.05),while the detection rate of BV among single vaginitis cases was higher in the age group≥40 years than in other age groups(P＜0.05).Conclusions:The vaginal microecol-ogy of infertile women varies in terms of infection rates across different age groups and seasons.Patients with simple vaginitis have the highest rate of VVC,while those with mixed vaginitis have the highest proportion of AV+BV infection.

Objective:To explore the relationship between sperm DNA integrity, semen parameters, seminal plasma neutral α-glucosidase activity and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. Methods:The clinical data of 300 male infertile patients who underwent routine semen analysis in the Second Affiliated Hospital of Air Force Medical University from October 2023 to April 2024 and whose spouses received IVF/ICSI treatment were retrospectively analyzed. The results of sperm DNA integrity [sperm DNA fragmentation index (DFI)], semen parameters (sperm percentage, sperm density, sperm motility, normal morphology sperm rate) and seminal plasma neutral α-glucosidase activity at admission were recorded. According to their spouses′ IVF/ICSI outcomes, the 300 patients were divided into the successful pregnancy group (those with successful intrauterine pregnancy detected by ultrasound 30 days after transplantation) and the unsuccessful pregnancy group (those without successful intrauterine pregnancy detected by ultrasound 30 days after transplantation). The differences in sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity at admission between the two groups were compared. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity in male infertile patients at admission for their spouses′ IVF/ICSI outcomes.Results:According to the IVF/ICSI outcomes of the spouses of male infertile patients, 169 cases (56.3%) had successful intrauterine pregnancy detected by ultrasound 30 days after transplantation; 131 cases (43.7%) had unsuccessful intrauterine pregnancy. At admission, there was no statistically significant difference in clinical data between the two groups (all P>0.05). The DFI and sperm density in the successful pregnancy group were lower than those in the unsuccessful pregnancy group, while the sperm percentage, sperm motility, normal morphology sperm rate and seminal plasma neutral α-glucosidase activity were higher than those in the unsuccessful pregnancy group (all P<0.05). The area under the ROC curve (AUC) values of single indicators including DFI, sperm percentage, sperm density, sperm motility, normal morphology sperm rate, and seminal plasma neutral α-glucosidase level in predicting the IVF/ICSI outcomes of spouses of male infertile patients were 0.719, 0.718, 0.812, 0.779, 0.769, and 0.736, respectively; the sensitivities were 70.42%, 77.46%, 69.01%, 70.42%, 69.01%, and 77.46%, respectively; the specificities were 66.38%, 55.02%, 81.22%, 73.80%, 77.29%, and 62.88%, respectively; the Youden indexes were 0.368, 0.325, 0.502, 0.442, 0.463, and 0.404, respectively; all differences were statistically significant (all P<0.05). Conclusions:Sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity can assist in predicting IVF/ICSI outcomes, providing an important reference for the treatment outcomes of male infertile patients.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.

Objective:To investigate the characteristic distribution of vaginal microbiota in infertile women.Methods:We collected the results of vaginal microbiological examinations from 19322 initial visit infertile women who visited the Reproductive Medicine Center of the Department of Obstetrics and Gynecology,the Second Affili-ated Hospital of Air Force Medical University from March 1,2023 to July 31,2024.The vaginal microbiota infection status of patients was compared in different age groups(＜25 years old,25-＜30 years old,30-＜35 years old,35-＜40 years old,≥40 years old)and different seasons(spring,summer,autumn,winter).Results:①Among 19322 women,6027 cases(31.19％)showed abnormal vaginal microecology.Pathogenic microorganisms were detected in 3093 cases,including 2882 cases of single vaginitis,211 cases of mixed vaginitis,3764 cases with vagi-nal cleanliness grade Ⅲ-Ⅳ,and 3965 cases with abnormal lactobacilli.Among patients with single vaginitis,1349 cases(46.81％)were diagnosed with vulvovaginal candidiasis(VVC),which was the highest proportion.Aerobic vaginitis(AV)followed with 752 cases(26.09％),and bacterial vaginosis(BV)had 671 cases(23.28％),trichomonal vaginitis(TV)with 110 cases(3.82％).Among patients with mixed vaginitis,AV+BV was the most common with 96 cases(45.49％).②The detection rates of cleanliness grade Ⅲ-Ⅳ,abnormal lactobacilli,abnor-mal microorganisms(unclear pathogen),single vaginitis(BV,VVC and TV),and mixed vaginitis showed statisti-cally significant differences across different seasons(P＜0.05).Specifically,the detection rates of cleanliness grade Ⅲ-Ⅳ and abnormal microorganisms(unclear pathogens)were significantly higher in autumn than in other seasons(P＜0.05),while the detection rate of abnormal lactobacilli was higher in spring than in other seasons(P＜0.05).③The detection rates of abnormal lactobacilli,abnormal microorganisms(unclear pathogen),single vaginitis(BV,VVC and AV),and mixed vaginitis showed significant differences among different age groups(P＜0.05).Specifically,the detection rate of abnormal microorganisms(unclear pathogen)was higher in the age group＜25 years than in other age groups(P＜0.05),while the detection rate of BV among single vaginitis cases was higher in the age group≥40 years than in other age groups(P＜0.05).Conclusions:The vaginal microecol-ogy of infertile women varies in terms of infection rates across different age groups and seasons.Patients with simple vaginitis have the highest rate of VVC,while those with mixed vaginitis have the highest proportion of AV+BV infection.

Objective:To explore the relationship between sperm DNA integrity, semen parameters, seminal plasma neutral α-glucosidase activity and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) outcomes. Methods:The clinical data of 300 male infertile patients who underwent routine semen analysis in the Second Affiliated Hospital of Air Force Medical University from October 2023 to April 2024 and whose spouses received IVF/ICSI treatment were retrospectively analyzed. The results of sperm DNA integrity [sperm DNA fragmentation index (DFI)], semen parameters (sperm percentage, sperm density, sperm motility, normal morphology sperm rate) and seminal plasma neutral α-glucosidase activity at admission were recorded. According to their spouses′ IVF/ICSI outcomes, the 300 patients were divided into the successful pregnancy group (those with successful intrauterine pregnancy detected by ultrasound 30 days after transplantation) and the unsuccessful pregnancy group (those without successful intrauterine pregnancy detected by ultrasound 30 days after transplantation). The differences in sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity at admission between the two groups were compared. The receiver operating characteristic (ROC) curve was used to analyze the predictive efficacy of sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity in male infertile patients at admission for their spouses′ IVF/ICSI outcomes.Results:According to the IVF/ICSI outcomes of the spouses of male infertile patients, 169 cases (56.3%) had successful intrauterine pregnancy detected by ultrasound 30 days after transplantation; 131 cases (43.7%) had unsuccessful intrauterine pregnancy. At admission, there was no statistically significant difference in clinical data between the two groups (all P>0.05). The DFI and sperm density in the successful pregnancy group were lower than those in the unsuccessful pregnancy group, while the sperm percentage, sperm motility, normal morphology sperm rate and seminal plasma neutral α-glucosidase activity were higher than those in the unsuccessful pregnancy group (all P<0.05). The area under the ROC curve (AUC) values of single indicators including DFI, sperm percentage, sperm density, sperm motility, normal morphology sperm rate, and seminal plasma neutral α-glucosidase level in predicting the IVF/ICSI outcomes of spouses of male infertile patients were 0.719, 0.718, 0.812, 0.779, 0.769, and 0.736, respectively; the sensitivities were 70.42%, 77.46%, 69.01%, 70.42%, 69.01%, and 77.46%, respectively; the specificities were 66.38%, 55.02%, 81.22%, 73.80%, 77.29%, and 62.88%, respectively; the Youden indexes were 0.368, 0.325, 0.502, 0.442, 0.463, and 0.404, respectively; all differences were statistically significant (all P<0.05). Conclusions:Sperm DNA integrity, semen parameters and seminal plasma neutral α-glucosidase activity can assist in predicting IVF/ICSI outcomes, providing an important reference for the treatment outcomes of male infertile patients.

Objective:To evaluate the clinical efficacy of transoral robotic surgery (TORS) in the treatment of malignant tongue base tumors.Methods:A multicenter study was conducted to collect and analyze the clinical data of patients with malignant tongue base tumors who underwent TORS at five otolaryngology-head and neck surgery centers in China, including Eye Ear Nose and Throat Hospital of Fudan University, Sun Yat-sen University Cancer Center, Tongji Hospital of Huazhong University of Science and Technology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, and the First Affiliated Hospital of China Medical University between January 2017 and January 2023. Among the patients, 38 were males and 11 were females, with a mean age of 59.0±8.8 years. Baseline characteristics, complications, and follow-up data were compared between groups. Independent sample t-tests or Mann-Whitney U tests was used for comparisons of continuous variables; chi-square tests or Fisher′s exact tests was applied for categorical variables. Survival analysis was performed using the Kaplan-Meier method to calculate overall survival and disease-free survival, and differences between groups were compared using the log-rank test. Results:Among the 49 patients, 41 (83.7%) were diagnosed with squamous cell carcinoma (SCC), with a p16 positive rate of 51.2% (21/41). There were no statistically significant differences between the p16-positive group ( n=21) and the p16-negative group ( n=20) in age, sex, or postoperative bleeding (all P>0.05). However, there was a significant difference in TNM stage between the two groups ( χ2=14.556, P=0.020), with the p16-positive group predominantly in stage I (66.7%) and the p16-negative group primarily in stages Ⅲ and Ⅳ (40.0% and 30.0%, respectively). The postoperative tracheotomy rate was 30.6% (15/49), and the incidence of postoperative bleeding was 6.1% (3/49). The 1-year and 3-year overall survival rates were 98.0% and 92.5%, respectively, while, the 1-year and 3-year disease-free survival rates were 89.2% and 84.9%, respectively. No significant differences were observed between the p16-positive and p16-negative groups in 3-year overall survival (100% vs. 83.8%, χ2=1.093, P=0.518) or 3-year disease-free survival (68.2% vs. 88.9%, χ2=2.161, P=0.382). Conclusion:TORS for malignant tongue base tumors demonstrates high clinical safety and favorable oncological outcomes.

Objective:To investigate the efficacy and feasibility of transoral robotic surgery (TORS) for resection of tumors in the parapharyngeal spaces.Methods:The clinical data of 57 patients who underwent TORS for parapharyngeal space tumors from September 2018 to February 2024 were retrospectively analyzed. These patients were treated at five medical institutions: The First Affiliated Hospital of China Medical University, Eye & ENT Hospital of Fudan University, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, and Sun Yat-sen University Cancer Center. The patients were 28 males and 29 females, aged 17-77 years (median age, 47 years). The pathological types, locations, and sizes of the tumors, operation time, intraoperative bleeding volumes, postoperative hospital stays, and postoperative complications were evaluated. The data were analyzed using SPSS 27.0 software.Results:Postoperative pathological examination revealed 11 types of benign tumors. Among 57 cases, 27 cases had their tumors in the prestyloid spaces, predominantly with pleomorphic adenoma ( n=17), and 30 cases in the retrostyloid spaces, predominantly with schwannoma ( n=22). The tumor volumes ranged from 0.6 to 130.1 cm3, the intraoperative bleeding volumes ranged from 5 to 1 000 ml, the operation time ranged from 20 to 390 min, and the postoperative hospital stays ranged from 2 to 25 days. The total costs for individual cases were 36 000-100 000 yuan, with the highest cost in the case suffering from cerebrovascular accident. Four patients(7.0%) had tracheotomy and 36(63.2%) had nasogastric tube placement. Among the 57 patients, 5 had postoperative cavity effusion, 2 had wound dehiscence, 2 had cerebrovascular accidents, 1 had Horner syndrome, and 2 had other complications. The patients were followed up for 1-67 months, with only 1 patient with intracranial and extracranial communication relapsed. Conclusion:TORS is a safe and feasible approach for treating parapharyngeal space tumors, offering advantages such as minimal invasiveness, reduced blood loss, and faster recovery. It is suitable for parapharyngeal space tumors of various pathological types and locations. The postoperative complications are manageable, with favorable long-term follow-up results and low recurrence rates.

Acidosis, regardless of hypoxia involvement, is recognized as a chronic and harsh tumor microenvironment (TME) that educates malignant cells to thrive and metastasize. Although overwhelming evidence supports an acidic environment as a driver or ubiquitous hallmark of cancer progression, the unrevealed core mechanisms underlying the direct effect of acidification on tumorigenesis have hindered the discovery of novel therapeutic targets and clinical therapy. Here, chemical-induced and transgenic mouse models for colon, liver and lung cancer were established, respectively. miR-7 and TGF-β2 expressions were examined in clinical tissues (n = 184). RNA-seq, miRNA-seq, proteomics, biosynthesis analyses and functional studies were performed to validate the mechanisms involved in the acidic TME-induced lung cancer metastasis. Our data show that lung cancer is sensitive to the increased acidification of TME, and acidic TME-induced lung cancer metastasis via inhibition of miR-7-5p. TGF-β2 is a direct target of miR-7-5p. The reduced expression of miR-7-5p subsequently increases the expression of TGF-β2 which enhances the metastatic potential of the lung cancer. Indeed, overexpression of miR-7-5p reduces the acidic pH-enhanced lung cancer metastasis. Furthermore, the human lung tumor samples also show a reduced miR-7-5p expression but an elevated level of activated TGF-β2; the expressions of both miR-7-5p and TGF-β2 are correlated with patients' survival. We are the first to identify the role of the miR-7/TGF-β2 axis in acidic pH-enhanced lung cancer metastasis. Our study not only delineates how acidification directly affects tumorigenesis, but also suggests miR-7 is a novel reliable biomarker for acidic TME and a novel therapeutic target for non-small cell lung cancer (NSCLC) treatment. Our study opens an avenue to explore the pH-sensitive subcellular components as novel therapeutic targets for cancer treatment.