Correlation of multiple inflammatory indices in peripheral blood with postoperative recurrence and metastasis in oral squamous cell carcinoma patients / 口腔疾病防治

Objective@#To investigate the associations of multiple immunoinflammatory markers in peripheral blood before and after operation, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic immune-inflammation index (SII) and systemic inflammatory response index (SIRI), with postoperative recurrence and metastasis in oral squamous cell carcinoma (OSCC) patients, to provide a reference for predicting the prognosis of OSCC patients.@*Methods@#This study was approved by the hospital ethics committee, and informed consent was obtained from the patients. A total of 160 patients with primary OSCC who underwent radical surgery were grouped according to preoperative lymph node metastasis, degree of differentiation, clinical T stage, and postoperative recurrence and metastasis. The last preoperative and 1-month postoperative routine blood test results of all the patients were collected to analyze the relationship between peripheral blood inflammatory indicators, including the NLR, PLR, LMR, SII, and SIRI, before and after surgery.The above clinicopathological indicators and postoperative recurrence and metastasis were evaluated in OSCC patients.@*Results@#Among the 160 patients, there was a significant difference in the preoperative SII between the preoperative lymph node metastasis group and the no metastasis group (P<0.05); the preoperative NLR, LMR, SII and SIRI were significantly different among the different differentiation degree groups (P<0.05); and the preoperative SIRI in the different clinical T stage groups were significantly different (P<0.05). The preoperative NLR, SII and SIRI were significantly different between the postoperative recurrence and metastasis group and the no recurrence and metastasis group (P<0.05). Postoperative peripheral blood inflammatory markers were not associated with postoperative metastasis and recurrence. Univariate Cox analysis revealed that among the preoperative peripheral blood inflammatory indicators, the preoperative NLR, PLR, SII and SIRI were the factors influencing recurrence and metastasis in OSCC patients. Multivariate Cox analysis revealed that the preoperative NLR was the only independent risk factor for recurrence and metastasis in OSCC patients among the preoperative peripheral blood inflammatory indicators.@*Conclusion@#Among the peripheral blood inflammatory indicators, the preoperative NLR is an independent risk factor for postoperative recurrence and metastasis in OSCC patients and has certain predictive value.

Study on the mechanism of estrogen regulating endometrial fibrosis after mechanical injury via miR-21-5p/PPARα/FAO axis.

BACKGROUND: Intrauterine adhesion (IUA) caused by endometrial mechanical injury has been found as a substantial risk factor for female infertility (e.g., induced abortion). Estrogen is a classic drug for the repair of endometrial injury, but its action mechanism in the clinical application of endometrial fibrosis is still unclear. OBJECTIVE: To explore the specific action mechanism of estrogen treatment on IUA. METHODS: The IUA model in vivo and the isolated endometrial stromal cells (ESCs) model in vitro were built. Then CCK8 assay, Real-Time PCR, Western Blot and Dual-Luciferase Reporter Gene assay were applied to determine the targeting action of estrogen on ESCs. RESULTS: It was found that 17ß-estradiol inhibited fibrosis of ESCs by down-regulating miR-21-5p level and activating PPARα signaling. Mechanistically, miR-21-5p significantly reduced the inhibitory effect of 17ß-estradiol on fibrotic ESCs (ESCs-F) and its maker protein (e.g., α-SMA, collagen I, and fibronectin), where targeting to PPARα 3'-UTR and blocked its activation and transcription, thus lowering expressions of fatty acid oxidation (FAO) associated key enzyme, provoking fatty accumulation and reactive oxygen species (ROS) production, resulting in endometrial fibrosis. Nevertheless, the PPARα agonist caffeic acid counteracted the facilitation action of miR-21-5p on ESCs-F, which is consistent with the efficacy of estrogen intervention. CONCLUSION: In brief, the above findings revealed that the miR-21-5p/PPARα signal axis played an important role in the fibrosis of endometrial mechanical injury and suggested that estrogen might be a promising agent for its progression.

Identification of novel prognostic indicators for oral squamous cell carcinoma based on proteomics and metabolomics.

BACKGROUND: The low 5-year survival rate of oral squamous cell carcinoma (OSCC) suggests that new prognostic indicators need to be identified to aid the clinical management of patients. METHODS: Saliva samples from OSCC patients and healthy controls were collected for proteomic and metabolomic sequencing. Gene expressed profiling was downloaded from TCGA and GEO databases. After the differential analysis, proteins with a significant impact on the prognosis of OSCC patients were screened. Correlation analysis was performed with metabolites and core proteins were identified. Cox regression analysis was utilized to stratify OSCC samples based on core proteins. The prognostic predictive ability of the core protein was then evaluated. Differences in infiltration of immune cells between the different strata were identified. RESULTS: There were 678 differentially expressed proteins (DEPs), 94 intersected DEPs among them by intersecting with differentially expressed genes in TCGA and GSE30784 dataset. Seven core proteins were identified that significantly affected OSCC patient survival and strongly correlated with differential metabolites (R2 > 0.8). The samples were divided into high- and low-risk groups according to median risk score. The risk score and core proteins were well prognostic factor in OSCC patients. Genes in high-risk group were enriched in Notch signaling pathway, epithelial mesenchymal transition (EMT), and angiogenesis. Core proteins were strongly associated with the immune status of OSCC patients. CONCLUSIONS: The results established a 7-protein signatures with the hope of early detection and the capacity for risk assessment of OSCC patient prognosis. Further providing more potential targets for the treatment of OSCC.

[Cox model analysis of curative effect and prognostic factors of oral robot-assisted RPLN dissection for head and neck malignancies].

PURPOSE: To investigate the efficacy and prognostic factors of oral robot-assisted retropharyngeal lymph node (RPLN) dissection in the treatment of head and neck malignancies. METHODS: Sixty-eight patients with head and neck malignant tumors who were treated in our hospital from January 2017 to December 2019 and followed up until December 2022 were treated by oral robot-assisted RPLN dissection. The clinical remission rate, clinical control rate, operation time, intraoperative blood loss, length of hospital stay, and the survival rate and survival time at 1, 2 and 3 years of follow-up were compared. SPSS 22.0 software package was used for statistical analysis of the data. RESULTS: All 68 patients with head and neck tumors were successfully treated by oral robot-assisted RPLN resection, and no complications such as postpharyngeal incision massive bleeding, Horner syndrome, aspiration pneumonia were found in all patients. The follow-up was 3 years, the survival time was(31.15±4.93) months, the survival rate was 91.18%(62/68) at the first year, 85.29%(58/68) at the second year and 70.59% (48/68) at the third year. There was no significant difference in 3-year survival rate among different genders, ages, disease types, primary lesions, exocapsular lymph node invasion and peripheral nerve invasion (P＞0.05). There were significant differences in the 3-year survival rate of different T stages, N stages, TNM stages, maximum diameter of invaded lymph nodes and vascular cancer thrombus(P＜0.05). Cox proportional risk regression model analysis showed that stage T3 to 4, stage N2b to 3, stage Ⅳb TNM, maximum diameter of invaded lymph node ＞6 cm and vascular cancer thrombi were independent risk factors affecting the 3-year survival rate of head and neck cancer patients after surgery(P＜0.05). CONCLUSIONS: Oral robotic assisted RPLN dissection has certain efficacy in the treatment of head and neck malignant tumors, but the survival rate of patients is affected by T stage, N stage, TNM stage, maximum diameter of invaded lymph nodes, vascular cancer thrombolus and other factors, which should be paid more attention in clinic.

[Influencing factors of nutritional status and change in 50 patients with oral squamous cell carcinoma during treatment].

PURPOSE: To investigate the changes of nutritional status in patients with oral squamous cell carcinoma(OSCC) and analyze the influencing factors during treatment. METHODS: Anthropometry (weight, BMI, waistline, middle circumference of left and right upper arms) and laboratory index(serum prealbumin, serum albumin, transferrins, 25-hydroxyvitamin D) were measured to represent the nutritional status of 50 patients with OSCC before operation, two days, one month and three months after operation. SPSS 24.0 software package was used for statistical analysis of the data, and influencing factors of nutrition risk in OSCC patient were analyzed with binary logistic regression model. RESULTS: Univariate and multivariate analysis showed that advanced age(OR=1.127,95%CI: 1.053-1.207), low educational level (OR=5.250, 95%CI: 1.147-21.796), smoking(OR=6.182, 95%CI: 1.631-23.433), alcohol use(OR=5.227, 95%CI: 1.336-20.450), chemoradiotherapy (OR=3.984, 95%CI: 1.199-13.242), free flap surgery (OR=8.000, 95%CI: 2.060-31.068), tracheostomy(OR=3.960, 95%CI: 1.069-14.671), cervical lymph node metastasis(OR=4.821, 95%CI: 1.418-16.399), buccal carcinoma(OR=9.000, 95%CI:1.140-71.038), tongue cancer(OR=7.200, 95%CI: 1.081-47.962), tumor stage T3-4(OR=3.542, 95%CI: 1.066-11.771) were independent influencing factors of the nutritional status of patients with OSCC. CONCLUSIONS: Aging, low educational level, smoking history and drinking history in the general demographic characteristics of patients, and chemoradiotherapy, free flap surgery, tracheostomy during treatment, as well as buccal carcinoma, tongue cancer, advanced stage and cervical lymph node metastasis are clinical characteristics, which affect the nutrition level during the treatment for OSCC patients.

A novel technique for moderate to severe intrauterine adhesions: A historical cohort study.

To evaluate the feasibility and efficiency of our novel technique, ultrasound guided hysteroscopic catheter dilation (US-HCD), for the treatment of moderate to severe intrauterine adhesion (IUA). A total of 126 patients diagnosed with IUA and met the enrollment criteria were admitted in this historical cohort study from June 1, 2016 to December 31, 2018. All patients were divided into 2 groups according to the surgical techniques used. Group A (n = 68) were treated with traditional hysteroscopic adhesiolysis with scissors (THA) and Group B (n = 58) were treated with US-HCD. Their data for the next 2 years following the initial surgery were analyzed. Safety and feasibility (operation time, surgical complications and the third-look hysteroscopic surgery rate), and post-operation efficacy (reduction of American Fertility Society [AFS] scores, pregnancy and live birth rates) were evaluated between groups. Between the groups, there was no statistically significant differences in basic preoperative information and AFS scores (P > .05). While there were significant differences in the operation time of the initial surgery (P < .05) and reduction of AFS scores (P < .05). No surgical complications were recorded and only 3 patients (5.2%) received a third-look hysteroscopy in Group B, while there were 6 cases of complications and 13 cases (19.1%) of third-look hysteroscopy in Group A, indicating significant differences between Groups (P < .05). Both groups exhibited comparable pregnancy rate, live birth rate and obstetric complications (P > .05). Our new technique is a safe, feasible and effective procedure for moderate to severe IUA patients, which can be mastered more quickly and easily by surgeons and applied in areas with less affluent economy and without hysteroscopic scissors, thus worthy of further study.

Long non-coding RNA TUG1 knockdown repressed the viability, migration and differentiation of osteoblasts by sponging miR-214.

The maxillofacial region in the human body is susceptible to fracture and corresponding soft tissue injury. In the current study, the effect of long non-coding RNA (lncRNA) taurine upregulated gene 1 (TUG1) on maxillofacial fracture development was investigated. In total, 50 patients diagnosed with maxillary fracture and 50 healthy volunteers were enrolled in this study. Participants' TUG1 expression level in serum was measured using reverse transcription-quantitative (RT-q)PCR. After transfection with small interfering (si)-TUG1, microRNA (miR)-214 mimic, miR-214 inhibitor, bone morphogenetic protein 2 (BMP2) mimic or a combination, the biological behavior of osteoblasts was evaluated using MTT, Transwell assays, RT-qPCR, flow cytometry and western blot analysis. Recovery experiments were used to explore the potential mechanism. Results demonstrated that TUG1 expression was decreased in the serum of patients with maxillary fractures. Knockdown of TUG1 repressed viability, migration and differentiation and induced apoptosis of osteoblasts. StarBase v2.0 revealed that TUG1 served as a sponge for miR-214 and BMP2 is a direct target of miR-214. Altogether, it was revealed that TUG1 expression was decreased in patients with maxillary fractures and TUG1 knockdown repressed the biological process of osteoblasts by sponging miR-214.

Qiu's Neiyi Recipe Regulates the Inflammatory Action of Adenomyosis in Mice via the MAPK Signaling Pathway.

BACKGROUND: The management of adenomyosis is challenging and limiting. Qiu's Neiyi recipe (Qiu) is a traditional Chinese medicine (TCM) prescription clinically used for endometriosis treatment in China, but the effect and mechanism of Qiu on adenomyosis are undefined. METHODS: An experimental adenomyosis model was induced in female neonatal ICR mice administrated with tamoxifen. The adenomyosis mice were divided into five groups: high-, middle-, and low-Qiu's group, danazol group, and model group. The mice just administrated with the solvent only (no tamoxifen or drugs) were served as the control group. After 28 days of administration, the body, uterine, spleen, and thymus weights of all mice were examined. Then, the myometrial infiltration and the expression of inflammatory factors were detected by histology examination, ELISA, and qRT-PCR in the uterus. In addition, the MAPK/ERK signaling pathway-related protein expression in adenomyosis mice was detected by immunohistochemical (IHC) staining, qRT-PCR, and western blotting. RESULTS: In experimental adenomyosis mice, Qiu treatment improved the symptoms of adenomyosis by reducing the myometrial infiltration and increasing the index of spleen and thymus. The elevated levels of IL-1ß, IL-6, and TNF-α in serum and uterus tissues of adenomyosis model mice were also decreased after Qiu treatment. The improvement of Qiu on the adenomyosis was achieved by inhibiting the activated MAPK/ERK signaling pathway, including reducing the mRNA and protein expressions of p-ERK/ERK, p-JNK/JNK, and p-p38/p38 in the uterus tissues. CONCLUSION: Qiu alleviated the inflammatory reaction and uterus histological changes in mice with adenomyosis, and the potential mechanism is through the inhibition of the MAPK/ERK signaling pathway. Qiu may be a promising treatment for adenomyosis.

[Effect of conservative treatment on jaw symmetry of children with unilateral condylar fracture].

PURPOSE: To investigate the effect of conservative treatment of unilateral condylar fractures on jaw symmetry in children. METHODS: Twenty-four children with unilateral condylar fractures were divided into control group and experimental group according to the treatment methods, with 12 cases in each group. The control group received surgery, and the experimental group received conservative treatment with intermaxillary traction combined with occlusal pads. The treatment effects of the two groups were compared, and the imaging improvement, three-dimensional structure of the jaw, mandibular motor and occlusal relationship, and facial nerve injury were compared after treatment. SPSS 17.0 software package was used for statistical analysis. RESULTS: There was no significant difference in the total effective rate, total effective rate of imaging, disturbance of occlusal relationship, and incidence of facial nerve injury between the two groups (P>0.05). The transverse diameter of the condyles was significantly longer in the experimental group than in the control group, and the width of the condyles and bony condylar deflection in the experimental group were significantly smaller than those in the control group (P<0.05). The degree of mouth opening after treatment in both groups was increased, which was more remarkably in the experimental group after treatment than in the control group (P<0.05). CONCLUSIONS: Children with unilateral condylar fractures can obtain similar treatment effects with surgical treatment with conservative treatment. After treatment, the children's mandibular motor function and jaw symmetry are well restored.

WITHDRAWN: Performance of cartilage cells in different types of mandibular condylar fractures.

The Accepted Manuscript version of this article (published on 10 June 2020) was withdrawn on 2 July 2020 due to concerns over data validity.

Chinese herbal medicine for premature ovarian insufficiency: A protocol for systematic review.

BACKGROUND: Premature ovarian insufficiency (POI) is the loss of function of the ovaries before age 40. Chinese herbal medicine (CHM) has been treating POI for long time. Therefore, we conduct this study to assess the efficacy and safety of CHM for POI. METHODS: Seven databases will be searched from inception to December 31, 2018: PubMed, Embase, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), China Biology Medicine disc (CBM), WanFang Database, and Chongqing Chinese Scientific Journal Database (CQVIP). Randomized controlled trials that used CHM will be included. Two reviewers will independently complete the study selection, data extraction, and study quality assessment according to Cochrane Collaboration. All the data will be analyzed using Review Manage 5.3 software. RESULTS: This study will generate a comprehensive summary on effectiveness and safety of CHM for POI. CONCLUSION: This study may be beneficial to health policymakers, clinicians, and patients with regard to the use of CHM in POI treatment. TRIAL REGISTRATION NUMBER: PROSPERO CRD 42019144629.

Treatment of menorrhagia due to aplastic anemia by hysteroscopic resection of endometrial functional layer and levonorgestrel-releasing intra-uterine system: Three case reports.

RATIONALE: In women, menorrhagia associated with aplastic anemia (AA) is secondary to thrombocytopenia and can be acute and severe. Endometrial ablation or hysterectomy has been reported to achieve beneficial results. However, serious limitations and long-term complications exist. We report this clinical case series with the aim of sharing our experiences and exploring a safe and effective way to treat abnormal uterine bleeding (AUB) AA women with future fertility desire. PATIENT CONCERNS: The 3 young patients aged 25 to 29 years old suffered from AUB secondary to AA. DIAGNOSIS: They were diagnosed with AA by bone marrow biopsy and presented with symptoms and signs of AUB without other identified causations. INTERVENTIONS: When the platelet count was between 30*10 /L∼50*10 /L after a blood transfusion, each patient received a hysteroscopic resection of endometrial functional layer and was fitted a levonorgestrel-releasing intra-uterine system (LNG-IUS) in uterine cavity following the surgery. OUTCOMES: All the patients recovered without incident and were discharged in clinically stable conditions. LESSONS: In conclusion, AUB secondary to AA can be acute and severe. Hemostasis is more difficult due to progressive pancytopenia. For young women with future fertility desire, LNG-IUS following hysteroscopic resection of endometrial functional layer is a safe and effective way against endometrial ablation or hysterectomy.

Natural killer cells inhibit metastasis of ovarian carcinoma cells and show therapeutic effects in a murine model of ovarian cancer.

Ovarian cancer has the highest mortality rate and is the most common of all gynecologic malignancies. Novel treatments for ovarian cancer are urgently required to improve outcomes and the overall survival of patients. The present study investigated whether immunotherapy with natural killer (NK) cells affected the survival of mice with ovarian cancer. Results analysis identified adjunctive NK cells as a potential therapeutic method in ovarian cancer. Patient-derived ovarian cells were isolated, cultured and subsequently injected subcutaneously into immune deficient BALB/c-nude mice. Human NK cells were isolated from peripheral blood mononuclear cells and cultured for expansion in vitro. The present results demonstrated that ovarian cells in BALB/c-nude mice did not induce spontaneous ovarian cancer cell metastasis in the NK-treated group. In addition, NK cells activated immune cells in the immune system, which resulted in inhibition of ovarian tumor growth in vitro and in a murine xenograft model of ovarian cancer. The data also indicated that cytotoxic activity of NK cells prevented migration and invasion of ovarian cancer cells, which contributed to prevention of systemic metastasis and suggested that NK cells could be effective cells for therapy against ovarian cancer. Furthermore, NK cells induced apoptosis and increased the number of cluster of differentiation (CD)4+, CD8+ as well as cytotoxic T lymphocyte responses by intravenous injection in a murine xenograft model of ovarian cancer. These results suggested that NK cells inhibited the systemic metastasis for ovarian cancer cells. In conclusion, the present study suggested that NK cell immunotherapy inhibited systemic metastasis of ovarian cancer cells and improved the survival rate of mice. Sufficient supplementation of NK cells may serve as a promising immunotherapeutic strategy for ovarian cancer.