[Characteristics and clinical analysis of MLH1 c.463dupC gene mutation in a Lynch syndrome family].

In this study, a case of Lynch syndrome (LS) family line with a novel mutation site in the MLH1 c.463dupC gene was reported and the clinical and pathogenic genetic features of this family were analyzed. A 40-year-old female patient with colon cancer diagnosed at the First Affiliated Hospital of Kunming Medical University on October 2, 2020 was retrospectively included. The clinical data of the family were collected and the family lineage was drawn. The family tumor history met the Amsterdam Criteria Ⅱ and the diagnostic criteria of LS in Chinese, which was a typical LS family lineage. A germline code-shift missense mutation c.463dupC in the MLH1 gene located in exon 6, a possible pathogenic variant, was detected by second-generation sequencing (NGS) in the patient. Subsequently, Sanger sequencing was performed on a total of 20 direct lineage members of the family of the MLH1 gene, 7 cases were found to harbor the mutation and included in the LS high-risk control. Follow-up to October 2023 showed that the patient had endometrial and cervical polyps, one case had colorectal cancer, and two cases had intestinal polyps, all were treated with early intervention and therapy; two cases did not show any clinical symptoms. This study is the first to report a new mutation site for the potentially pathogenic MLH1 c.463dupC, providing a rationale for the pathogenicity of the mutation and standardized health management for familial carriers.

Effect of PI3K/AKT/HIF-1α signaling pathway on oxidative stress and apoptosis in nucleus pulposus cells.

OBJECTIVE: The aim of the study was to explore the expression of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB/AKT)/hypoxia-induced factor-1 alpha (HIF-1α) signaling pathway and the apoptosis of nucleus pulposus cells (NPCs) under different oxygen concentrations to clarify the biological characteristics of NPCs and the molecular mechanism of intervertebral disc degeneration (IVDD). MATERIALS AND METHODS: Normal and degenerated human NPCs were collected. Leibovitz's medium with 100 µmol/L CoCl2 was used to establish a hypoxic culture environment, and 100 µmol/L H2O2 was used to establish an oxidative stress culture environment. Third-generation NPCs were divided into 6 groups: normal NPCs + hypoxia, normal NPCs + normoxia, normal NPCs + oxidative stress, degenerated NPCs + hypoxia, degenerated NPCs + normoxia, and degenerated NPCs + oxidative stress. Normal NPCs + hypoxia was used as the experimental control group. Cell viability and proliferation were detected by using the Cell Counting Kit-8 (CCK-8) method. Cell apoptosis rate was assessed by flow cytometry, and expression levels of PI3K, AKT, and HIF-1α were determined by Real-Time-Polymerase Chain Reaction (RT-PCR) and Western blotting. RESULTS: The cell proliferation rate of both normal and degenerated NPCs decreased with increasing oxygen concentration. Conversely, the apoptosis rate increased as the oxygen concentration increased (p<0.05). Compared with the control group, whether the cells degenerated had a very significant impact on the apoptosis rate (p<0.001), and oxygen concentration also had a highly significant impact on both the cell proliferation rate and apoptosis rate (both p<0.001). The interaction between cell degeneration and oxygen concentration significantly affected both cell proliferation and apoptosis rates (p<0.05). Considering the expression levels of PI3K, AKT, and HIF-1α, normal NPCs had the highest levels under low oxygen concentrations, followed by oxidative stress and normoxia. In degenerated NPCs, the expression levels also decrease as the oxygen concentration increases. CONCLUSIONS: The PI3K/Akt/HIF-1α signaling pathway plays a significant role in inhibiting oxidative stress, antagonizing NPC apoptosis, and consequently delaying IVDD.

[Comparison of the impact of orthodontic treatment on pulp volume in adolescents and adults].

Objective: To compare the impact of orthodontic treatment on pulp volume in adolescents and adults. Methods: Cone-beam CT data of 62 patients undergoing orthodontic treatment at the Department of Orthodontics, Stomatological Hospital of Chongqing Medical University, from January 2019 to March 2022 were collected. Patients were divided into two age groups (31 patients in each group): adolescent group (aged 13-17, 17 males and 14 females) and adult group (aged 21-25, 12 males and 19 females). Pre-and post-treatment reconstructions of the pulp and dental tissues of upper first molars (UM1) and lower central incisors (L1) were performed. Measurements included pulp volume for UM1 (UM1 P) and L1 (L1 P), pulp chamber volume (UM1 PC) and root canal volume (UM1 RC) for UM1, root length for L1 (L1 RL), and mesiobuccal root length for UM1 (UM1 RL), as well as chamber heights at specific landmarks [the lengths from the central fossa fusion site to the roof of the pulp chamber (H1), the floor of the pulp chamber (H2), the nearest point of root divergence as well as crown-root bifurcation (H3), the farthest point of root divergence (H4), and the pulp chamber height (H5)] in UM1. Changes in these indices were calculated and analyzed using paired and independent sample t-tests for within-group and between-group differences, respectively. Pearson correlation was used to assess potential associations among H5, root length, and pulp volume changes. Results: Before and after orthodontic treatment, no significant difference was observed in the adult group for L1 P (t=-0.03, P=0.975), while significant differences were noted for UM1 P, UM1 PC, and UM1 RC (t=9.98, P<0.001; t=9.04, P<0.001; t=6.69, P<0.001). In the adolescent group, significant differences were found for both L1 P and UM1 P (t=2.25, P=0.029; t=6.30, P<0.001). After orthodontic treatment, the absolute value changes of UM1 P, UM1 PC, and L1 P in the adolescent group were (19.75±9.58), (15.07±7.65) and (1.89±6.29) mm3, respectively, and in the adult group were (13.33±9.41), (9.16±7.05) and (0.02±4.66) mm3, respectively (t=3.77, P<0.001; t=4.48, P<0.001; t=2.34, P=0.048). There was no significant absolute difference in the amount of UM1 RC between the two groups after orthodontic treatment (t=0.86, P=0.391). Before and after orthodontic treatment, the absolute value changes of L1 RL, H1 and H5 in the adolescent group were (0.54±0.41), (0.38±0.27) and (0.71±0.33) mm, respectively, and the absolute value changes in the adult group were (0.78±0.62), (0.26±0.20) and (0.57±0.28) mm, respectively (t=-2.43, P=0.017; t=2.96, P=0.004; t=2.57, P=0.011). Whereas no significant differences were observed for UM1 RL, H2, H3, and H4 (t=-0.85, P=0.400; t=0.43, P=0.669; t=-0.50, P=0.619; t=1.46, P=0.148). Additionally, significant correlations were found between changes in H5 and UM1 RL with UM1 P (r=0.35, P<0.001; r=0.19, P=0.030), but not between Changes in L1 RL and L1 P (r=0.11, P>0.05). Conclusions: The effect of orthodontic treatment on pulp volume in adolescents and adults were different.

Comparison of efficacy and safety of flexible ureteroscopy and mini-percutaneous nephrolithotomy for 2-3 cm renal calculi in women: a single-center study.

OBJECTIVE: This study aimed to compare the efficacy and safety of flexible ureteroscopic lithotripsy (FURSL) and mini-percutaneous nephrolithotomy (mPCNL) in the treatment of 2-3 cm renal calculi in women. PATIENTS AND METHODS: Clinical data of 186 patients who underwent mPCNL (n=96) and FURSL (n=90) surgery in our hospital from June 2018 to February 2023 were collected. Several parameters were assessed and compared between the two groups, including operation duration, length of hospital stay, cost of hospitalization, pain intensity measured by the visual analogue scale (VAS), patient comfort assessed using the Bruggrmann Comfort Scale (BCS), decrease in hemoglobin levels, changes in blood urea nitrogen (BUN), fluctuations in serum creatinine (Scr), hypersensitive C-reactive protein (hs-CRP) levels, complication rates, immediate post-operative stone-free rate (RSFR), and long-term stone-free rate (LSFR). RESULTS: The comparative analysis of patient age, body mass index (BMI), stone size, computed X-ray tomography (CT) value of stones, number of stones, and comorbidities revealed no statistically significant differences between the mPCNL and FURSL groups (p>0.05). The mPCNL cohort exhibited a markedly lower duration of operation (p<0.001) and BCS score (p<0.001) compared to the FURSL cohort. Nonetheless, the mPCNL cohort demonstrated significantly higher hospitalization expenses (p<0.001), length of hospital stay (p<0.001), VAS score for pain (p<0.001), and level of hemoglobin decrease (p<0.001) in comparison to the FURSL cohort. Moreover, the immediate post-operative stone-free rate (RSFR) was significantly higher in the mPCNL group (p=0.007). The long-term stone-free rate (LSFR), however, showed no significant difference between the two groups (p=0.160). Furthermore, the FURSL group exhibited significantly fewer overall complications in contrast to the mPCNL group (p=0.006). CONCLUSIONS: mPCNL and FURSL are both safe and effective surgical methods for treating 2-3 cm renal calculi in women. However, FURSL holds distinct advantages, including minimally invasive procedure, accelerated recovery, reduced cost, and lower incidence of complications.

[CT texture analysis for predicting pseudoprogression in metastatic clear cell renal cell carcinoma during PD-1 inhibitor therapy].

Objective: To evaluate the effectiveness of enhanced CT texture feature analysis in predicting pseudoprogression in patients with metastatic clear cell renal cell carcinoma (mccRCC) undergoing programmed cell death protein 1 (PD-1) inhibitor therapy. Methods: A cross-sectional study. Data from 32 patients with mccRCC were retrospectively collected who received monotherapy with PD-1 inhibitors after standard treatment failure at Henan Cancer Hospital, from June 2015 to January 2021. Clinical information and enhanced CT images were analyzed to assess target lesion response. The lesions were divided into pseudoprogression and non-pseudoprogression groups. Manual segmentation of target lesions was performed using ITK-Snap software on baseline enhanced CT, and texture analysis was conducted using A.K. software to extract feature parameters. Differences in texture features between the pseudoprogression and non-pseudoprogression groups were analyzed using univariate and multivariate logistic regression. A predictive model for pseudoprogression was constructed, and its performance was evaluated using ROC curve analysis. Results: A total of 32 patients with 89 lesions were included in the study. Statistical analysis revealed significant differences in seven texture features between the pseudoprogression and non-pseudoprogression groups. These features included"original_ngtdm_Strength"(0.49 vs. -0.61,P=0.006), "wavelet-HLH_glszm_ZonePercentage"(0.67 vs. -0.22,P=0.024),"wavelet-LHL_ngtdm_Strength"(1.20 vs. -0.51,P=0.002), "wavelet-HLL_gldm_LargeDependenceEmphasis"(-0.84 vs. 0.19,P=0.002), "wavelet-HLH_glcm_Id" (-0.30 vs. 0.43,P=0.037),"wavelet- HLH_glrlm_RunPercentage"(0.45 vs. -0.01,P=0.032),"wavelet-LHH_firstorder_Skewness"(0.25 vs. -0.27, P=0.011). Based on these features, a pseudoprogression prediction model was developed with a P-value of 0.000 2 and an odds ratio of 0.045 (95%CI 0.009-0.227). The model exhibited a high predictive performance with an AUC of 0.907 (95%CI 0.817-0.997) according to ROC curve analysis. Conclusions: Enhanced CT texture feature analysis shows promise in predicting lesion pseudoprogression in patients with metastatic ccRCC undergoing PD-1 inhibitor therapy. The developed predictive model based on texture features demonstrates good performance and may assist in evaluating treatment response in these patients.

[Effect and safety of endobronchial placement of vaseline gauze in the treatment of patients with bronchial fistula].

Objective: To investigate the application of vaseline gauze to occlude the bronchial fistulas and its clinical effectiveness and safety in this retrospective study. Methods: This study retrospectively reviewed the clinical records of 14 patients with bronchial fistulas at Department of Respiratory and Critical Care Medicine, Shanghai Dongfang Hospital affiliated to Tongji University between June 2019 and June 2022. Seven of the 14 patients were female, and the age ranged from 16 to 74 years. We retrieved all the clinical records of all the enrolled patients during the 6 to 12 months follow-up after the operation, including the information for removal of chest drainage pipe, the failure of endobronchial blockage using vaseline gauze, as well as the complications (migration of the vaseline gauze, obstructive pneumonia, pulmonary atelectasis, et. al.) after the operation. Results: Of the 14 patients, 3 patients had fistula located in main or lobar bronchi; 10 patients had fistula located in distal airways; and 1 patient had fistula located both in main bronchi and distal airways. Ten patients were complicated with pneumonia or pleural cavity infections; Five were complicated with pneumothorax or hydropneumothorax. All of the 14 patients achieved successful airway occlusion after the placement of vaseline gauze in the responsible bronchial airways or stumps for the fistulas. Eleven of the 14 patients successfully removed the drainage tube for the residual cavity, 3 of the 14 patients successfully removed the vaseline gauze for the fistula which was healing during the follow up of 6-12 months. No one of the patients had severe complications or treatment failure. Conclusion: Bronchial placement of vaseline gauze might be a feasible and effective technique for treatment of bronchial fistulas.

[Clinicopathological characteristics and differential diagnosis of 6 cases of congenital granular cell tumor].

To provide references for the diagnosis and treatment of congenital granular cell tumor (CGCT), by comprehensive analysis of the clinical data, histopathological and immunohistochemical results. Patients with CGCT were involede, from March 2015 to November 2020, at the Department of Oral and Maxillofacial Surgery of the First Affiliated Hospital of Zhengzhou University. A total of 6 children, aged 3-16 days, 1 male and 5 female, 5 maxillary and 1 mandibular, with maximum tumor diameter of 6-70 mm, were included. The lesions of CGCT were single and connected to the alveolar ridge by a pedicle. The surface of the tumor was covered with a vascular network, and two cases had ulcers on the surface of the tumor. All 6 cases had the tumor removed surgically and there was no recurrence or metastasis in the follow-up visit. Although CGCT is rare, it is a benign tumor and generally does not recur or metastasize after surgery, and has a good prognosis. The prenatal imaging, clinical manifestations after delivery, pathological characteristics and immunohistochemical analyses may provide reference for early diagnosis and treatment of CGCT.

Biochemical-thermal-hydro-mechanical coupling model for aerobic degradation of landfilled municipal solid waste.

Ventilating solid waste landfills with an oxygen supply can effectively accelerate the degradation of waste, achieve rapid stabilization, and realize the sustainable utilization of landfills. Aiming to understand and verify the aerobic degradation process in landfills, this paper proposed a biochemical-thermal-hydro-mechanical coupling model. The model considers aerobic biochemical reactions, dissolved solute migration, heat transport, two-phase flow, and skeleton deformation. The model was verified by comparison with an in-situ experiment at Jinkou landfill. The results showed the model could accurately represent the observed degradation phenomena during the experiment. The modelling results indicated that the rate of temperature increase and peak temperature of the upper layer, which were lower than those of the middle layer, were affected by heat exchange at the landfill surface. The lowest temperatures occurred near the bottom because of high water content and low oxygen concentrations. The high temperature zone migrated out from the injection well during degradation, reflecting the degradation of degradable organic matter associated with oxygen diffusion rates and aerobic degradation reactions. The initial accumulated settlement value was fast, but slowed and finally stabilized. The surface subsidence also developed from the center around the injection well to the surrounding area, and 70% of the total subsidence occurred within 150 days. This newly developed model provides a theoretical framework for analyzing the multi-field coupling of aerobic degradation of landfilled municipal solid waste (MSW).

Comparison of different radiomic models based on enhanced T1-weighted images to predict the meningioma grade.

AIM: To compare different models in predicting meningioma grade based on enhanced T1-weighted images. MATERIALS AND METHODS: One hundred and eighty-eight patients with meningioma were analysed retrospectively. There were 94 high-grade meningiomas which formed the high-grade group comprising 68 World Health Organization (WHO) grade II meningiomas and 26 WHO grade III meningiomas. Ninety-four low-grade meningiomas were selected randomly to form the low-grade group. Least absolute shrinkage and selection operator (LASSO) regression was used to reduce the dimensions of the texture parameters. Support vector machine (SVM), decision tree (DT), conditional inference trees (CIT), random forest (RF), k-nearest neighbours (KNN), back-propagation neural network (BPNet), and Bayes were used to construct models. Receiver operating characteristic (ROC) analysis and decision curve analysis (DCA) was applied and compared among different models. RESULTS: Every model performed well and had a high area under the ROC curve (AUC; all >0.80). In the seven models, the highest accuracy was obtained with SVM and KNN (0.79), the highest sensitivity was obtained with DT and Bayes (0.85), and the highest specificity was obtained with SVM and CIT (0.83). SVM and RF had the highest AUC (0.884). KNN had the largest net benefit when the threshold probability was <0.50, whereas SVM had the largest net benefit when the threshold probability was >0.50. CONCLUSIONS: Different radiomic models based on enhanced T1-weighted images can be used to predict meningioma grade. The model of SVM and KNN performed better than other models with a larger net benefit.

[Current trends of dust exposure and autoimmune diseases: a bibliometric and visual analysis].

Objective: To analyze the distribution and key words of the literature about dust exposure related autoimmune diseases published in Chinese and foreign languages. Methods: In May 2021, Publications were retrieved from the PubMed、the Web of Science Core Collection database, SinoMed and CNKI Note Express and VOS viewer were used to evaluate and visualize the results. Results: 89 literatures were retrieved in Chinese from 1974 to 2020, and 545 literatures were retrieved in foreign languages from 1954 to 2020. The country with the most published literatures in foreign languages was the United States, total 132 litaratures were retrieved (24.86%) . A total of 366 journals at home and abroad have published research results on dust exposure and autoimmune diseases. Keyword analysis prompts this area of research focuses on silica exposure, silicosis, asbestosis, antinuclear antibodies, systemic sclerosis, rheumatoid arthritis, etc. Conclusion: The research on dust exposure and autoimmune diseases is on the rise at home and abroad, and the focus is the epidemiology, clinical characteristics and mechanism of occupational exposure, dust, silicosis and so on.

[Preliminary efficacy and safety analysis of carrelizumab combined with apatinib in patients with middle-advanced liver cancer progressed after drug-eluting beads-transcatheter arterial chemoembolization].

Objective: To explore the preliminary clinical efficacy and safety of calerizumab combined with apatinib in the treatment of patients with middle-advanced liver cancer whose disease has progressed after drug-eluting beads-transcatheter arterial chemoembolization (D-TACE). Methods: A retrospective analysis of 23 patients with advanced liver cancer after D-TACE who were treated with carrelizumab combined with apatinib from April 2019 to July 2020 at Lianyungang First People's Hospital was carried out. There were 15 males and 8 females with a mean age of (62±9) years. The clinical efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECRST), and treatment-related adverse events were analyzed after treatment. Results: All the patients received D-TACE therapy with an average of (2.6±1.0) times, TACE-refractory tumor was observed in 7 patients, and distant metastasis was seen in 6 patients. The objective response rates after combined treatment of 1 month and 3 months were 47.8% and 60.9%, respectively. Disease control rate (DCR) was 73.9% and 78.3%, respectively; median progression-free survival (mPFS) was 126 days. Among 18 patients with alpha fatoprotein (AFP)>200 µg/L, the values before and after treatment of 2 months was (497±117) µg/L and (80±19) µg/L, respectively (P<0.05). Among 9 patients of vascular endothelial growth factor (VEGF)>142.2 ng/L, the values before and after treatment of 2 months was (154±51) ng/L and (57±19) ng/L, respectively (P<0.05). The incidence of treatment-related adverse events was 87.0% (20/23). All adverse reactions did not exceed grade 3 and could be controlled by symptomatic supportive treatment or reducing the dose of apatinib,and the serum aspartate aminotransferase (AST) level after treatment of 3 months[(77±33) U/L] was higher than that before treatment [(45±26) U/L] (P<0.05). Conclusion: For patients with advanced liver cancer after D-TACE, the treatment of carrelizumab combined with apatinib is effective and the adverse reactions are controllable.

[Research progress of silica-associated autoimmune diseases].

Silicosis is caused by long-term exposure to dust containing crystalline silica. However, silica exposure, which may lead to autoimmune dysfunction, is associated with autoimmune diseases such as rheumatoid arthritis, systemic sclerosis, systemic lupus erythematosus, idiopathic inflammatory myopathy and anti-central granulocyte cytoplasmic antibody associated vasculitis. With silica exposure autoimmune diseases may exist with or without silicosis. This article reviews recent research on silica-associated autoimmune diseases such as the concept, epidemiology, clinical characteristics and potential mechanisms to improve the understanding of the disease and promote the formulation of diagnostic criteria and treatment plans.

[Research progress of hepatocyte transplantation treatment for alpha-1 antitrypsin deficiency].

Alpha-1 antitrypsin deficiency is an autosomal codominant genetic disease characterized by low levels of alpha-1 antitrypsin in the blood. Clinically, in young patients, it mainly manifests as emphysema, acute/chronic liver injury and liver cancer. The treatment methods include symptomatic treatment and alpha -1 antitrypsin supplementation. However, the existing treatment cannot prevent the liver fibrosis progression. At present, more than ten cases of the disease have been reported in China, but the understanding of this disease is still indecisive. Moreover, there exists no biotherapy drug for this disorder. This article introduces the research progress of hepatocyte transplantation treatment for this disorder.

[Research progress on immune efficacy, safety, vaccination intention and immunization strategy of domestic enterovirus 71 vaccine after its marketing].

Enterovirus 71 (EV71) is one of the main pathogens of hand, foot and mouth disease (HFMD) and the main pathogen of severe HFMD. In 2015, three EV71 vaccines were successively marketed in China as powerful prevention and control tools for HFMD caused by EV71. To understand the efficacy, immunogenicity, safety and quality stability of the domestic EV71 vaccine after entering into the market and analyze potential problems in its application, this article incorporates research regarding the immune effect, population effect, safety, quality testing and evaluation results, vaccination willingness and vaccination behavior survey to explore the vaccination strategies for the donll stic EV71 vaccine. EV71 vaccine has good immunogenicity, safety, protective efficacy, and good quality stability after entering into the market, however, only a few study focused on its safety when inoculating with other immunization planning vaccines simultaneously. Strengthen safety monitoring and discuss the safety of the EV71 vaccine especially when simultaneously inoculate with other immunization program vaccines are still necessary. Enterovirus evolution and recombination, whilst the probable impact of the EV71 vaccine can be the reason for future changes of HFMD epidemic strains, hence continuous monitoring of antigenic mutations and genetic evolution of enterovirus should be responded to. Encouraging the R&D of polyvalent vaccines against HFMD is also necessary. Parents' lack of HFMD and EV71 vaccine knowledge was common, therefore HFMD knowledge should be strengthened at the same time when introducing the EV71 vaccine to the public. Also, it should be emphasized that the EV71 vaccine can only prevent HFMD caused by EV71.

miR-92a-3p promotes the proliferation and invasion of gastric cancer cells by targeting KLF2.

MicroRNAs (miRNAs) have pivotal roles in the initiation and progression of gastric cancer (GC), and miR-92a-3p has been proved to act as an oncogene in multiple malignancies. However, the molecular mechanisms by which miR-92a-3p contributes to GC remain unclear. The differentially expressed miRNAs were screened by GEO dataset, and the association of miR-92a-3p expression with clinicopathological characteristics and prognosis in patients with GC was analyzed by TCGA dataset. The target genes of miR-92a-3p were identified by bioinformatic analysis, and their interaction was confirmed by luciferase reporter assay. MTT, EdU and Transwell assays were conducted to determine the role of miR-92a-3p in GC cells. As a result, it was found that the expression levels of miR-92a-3p were increased in GC tissues and were associated with tumor size, lymph node infiltration and distant metastasis, acting as an independent prognostic factor of poor survival in patients with GC. Restored expression of miR-92a-3p facilitated cell proliferation, DNA synthesis and cell invasion, but its inhibitor reversed these effects. KLF2 was further identified as a direct target of miR-92a-3p, indicating a negative correlation with miR-92a-3p expression and harboring a favorable prognosis in GC. In addition, KLF2 repressed cell proliferation and invasion and attenuated the tumor-promoting effects of miR-92a-3p in GC cells. Altogether, our findings demonstrated that miR-92a-3p promoted the proliferation and invasion of GC cells by targeting KLF2.