To adapt to the immune environment and the stress of antimicrobial exposure,Klebsiella pneumoniae can evolve into resistance to multiple antimicrobial agents in the hosts.However,less attention has been paid to the genetic evolution in vivo from antimicrobial susceptibility to resistance.This paper reviews the adaptive evolu-tion of drug resistance and virulence of K.pneumoniae in patients in current clinical practice.The potential mecha-nisms of the evolution of resistance to carbapenems,ceftazidime-avibactam,tigecycline and colistin in human hosts were mainly summarized.

Objective To explore the expression levels of CD33⁺ myeloid-derived suppressor cell (MDSC)-mediated T lymphocyte function and related inflammatory factors secreted by T lymphocyte subsets in patients with cervical cancer, and to analyze their correlation with the treatment efficacy of ¹²⁵I particle implantation combined with arterial chemoembolization, as well as predictive value for treatment outcomes and interaction effects. Methods From January 1st, 2021 to January 1st, 2024, our hospital admitted 152 patients with advanced cervical cancer, who were confirmed by pathological examination. All patients received uterine artery chemoembolization combined with ¹²⁵I particle implantation. The predictive value of CD33⁺MDSC levels for clinical treatment response in cervical cancer was assessed using receiver operating characteristic (ROC) curve analysis. Multivariate logistic regression analysis was performed to evaluate both multiplicative and additive interactions between CD33⁺MDSC and T lymphocytes in predicting clinical treatment failure of cervical cancer. Kaplan Meier method was used to analyze the survival differences between cervical cancer patients with high and low CD33⁺MDSC expression levels. Results Compared with the effective group, patients in the ineffective group had decreased expression levels of CD3⁺ T lymphocyte, CD4⁺ T lymphocyte, interleukin 2 (IL-2) and interferon γ (IFN-γ), while showing increased expression levels of CD33⁺MDSC, CD8⁺ T lymphocyte, IL-4 and IL-6, along with increased tumor necrosis factor α (TNF-α) levels, larger maximum tumor diameters, and a higher incidence of lymph node metastasis. The expression levels of CD33⁺MDSCs demonstrated good predictive performance for treatment efficacy in cervical cancer patients. The high CD33⁺MDSC expression group had a significantly shorter overall survival (OS) than the low CD33⁺MDSC expression group (6.0±1.0 months vs. 12.0±1.2 months; t=33.280). The interaction analysis revealed that CD33⁺MDSCs and CD8⁺ T lymphocytes were highly expressed, while CD3⁺ and CD4⁺ T lymphocytes were lowly expressed, which was associated with an increased risk of clinical treatment failure in cervical cancer patients. Conclusion CD33⁺MDSCs can inhibit CD3⁺ and CD4⁺ T lymphocytes. It can upregulate the expression of CD8⁺ T lymphocytes, form an immunosuppressive microenvironment, and reduce the treatment response rate of ¹²⁵I particle implantation combined with arterial chemoembolization. CD33⁺MDSCs may serve as an independent biomarker for predicting the therapeutic efficacy and poor prognosis.
Humans ; Female ; Uterine Cervical Neoplasms/immunology* ; Middle Aged ; Chemoembolization, Therapeutic/methods* ; Sialic Acid Binding Ig-like Lectin 3/immunology* ; Adult ; T-Lymphocytes/immunology* ; Aged ; Treatment Outcome

Objective:To investigate the effect of anterior cervical discectomy and fusion(ACDF)and cervical spine stability in patients with two-segment cervical spondylosis.Methods:The clinical data of 60 patients with two-level cervical spondylotic myelopathy in Anqing Municipal Hospital were analyzed retrospectively.They were divided into group A(30 cases)and group B(30 cases)according to the communication results between doctors and patients.The control group was given anterior cervical corpectomy and fusion(ACCF),and the observation group was given ACDF.The clinical effects(cervical brace protection time,hospital stay,operation time and intraoperative blood loss),postoperative pain degree[visual analogue score(VAS)],neurological function[Japanese Association of Orthopaedic Surgeons(JOA)],cervical spine function[cervical spine dysfunction index(NDI)],cervical spine stability(C3-6 segment Cobb angle,intervertebral height and cervical spine curvature)and complication rate were compared between the two groups.Results:There were no significant differences in cervical brace protection time,hospital stay and operation time between the two groups(P>0.05).The VAS score in ACDF group was lower than that in ACCF group at 1,3 and 6 months after operation(t=4.312,3.864 and 9.338,P<0.05).The JOA score was higher than that of ACCF group(t=6.482,6.366,5.059,P<0.05).The NDI score was lower than that of ACCF group(t=4.922,6.178,8.859,P<0.05).Six months after operation,the Cobb angle,intervertebral height and cervical curvature of cervical vertebra 3-6(C3-6)in ACDF group were higher than those in ACCF group.The difference was statistically significant(t=5.011,2.171 and 3.386,P<0.05).The incidence of complications between the two groups was not different(P>0.05).Conclusion:ACDF for two-segment cervical spondylosis can effectively improve cervical spine function and nerve function,reduce postoperative pain,and reduce intraoperative blood loss,which is safe and effective.

Objective:To investigate the effect of quercetin(QUE)on immune escape of gastric cancer cells by regulating the programmed death protein-1/programmed death ligand-1(PD-1/PD-L1)signaling pathway.Methods:Different concentrations of QUE(0～160 μmol/L)were applied to gastric cancer cell HGC-27,the cell survival rate was measured to screen for the optimal drug con-centration.HGC-27 cells were stochastically grouped into HGC-27 group,QUE low concentration(QUE-L)group,QUE medium con-centration(QUE-M)group,QUE high concentration(QUE-H)group,QUE-H+pcDNA-NC group(negative control for overexpres-sion of PD-1),and QUE-H+pcDNA-PD-1 group(overexpression of PD-1).Cell proliferation activity was analyzed by CCK-8 assay and colony formation assay.Apoptosis rate was detected by flow cytometry.The expression levels of proteins related to the PD-1/PD-L1 signaling pathway were detected by Western blot.Each group was co-cultured with NK cells,and the HGC-27 co-culture group,QUE-L co-culture group,QUE-M co-culture group,QUE-H co-culture group,QUE-H+pcDNA-NC co-culture group,and QUE-H+pcDNA-PD-1 co-culture group were constructed.NK cell killing rate was detected.ELISA was applied to detect the expression levels of IL-2,IFN-γ and TNF-α in various cell culture media.Results:Compared with the HGC-27 group,the cell survival rate,clone formation quantity,and PD-1 and PD-L1 expression levels in the QUE-L group,QUE-M group and QUE-H group were gradually decreased(P<0.05),while the cell apoptosis rate gradually increased(P<0.05).Moreover,the NK cell killing rate and the expression levels of IL-2,IFN-γ and TNF-α in the cell culture medium of the QUE-L co-culture group,QUE-M co-culture group,and QUE-H co-culture group gradually increased compared to the HGC-27 co-culture group(P<0.05).On the basis of high concentration QUE treatment of HGC-27 cells,overexpression of PD-1 reversed the trend of changes in the above indicators(P<0.05).Conclusion:QUE may inhibit immune escape of gastric cancer cells by down-regulating PD-1/PD-L1 signaling pathway.

Objective:To investigate the effect of quercetin(QUE)on immune escape of gastric cancer cells by regulating the programmed death protein-1/programmed death ligand-1(PD-1/PD-L1)signaling pathway.Methods:Different concentrations of QUE(0～160 μmol/L)were applied to gastric cancer cell HGC-27,the cell survival rate was measured to screen for the optimal drug con-centration.HGC-27 cells were stochastically grouped into HGC-27 group,QUE low concentration(QUE-L)group,QUE medium con-centration(QUE-M)group,QUE high concentration(QUE-H)group,QUE-H+pcDNA-NC group(negative control for overexpres-sion of PD-1),and QUE-H+pcDNA-PD-1 group(overexpression of PD-1).Cell proliferation activity was analyzed by CCK-8 assay and colony formation assay.Apoptosis rate was detected by flow cytometry.The expression levels of proteins related to the PD-1/PD-L1 signaling pathway were detected by Western blot.Each group was co-cultured with NK cells,and the HGC-27 co-culture group,QUE-L co-culture group,QUE-M co-culture group,QUE-H co-culture group,QUE-H+pcDNA-NC co-culture group,and QUE-H+pcDNA-PD-1 co-culture group were constructed.NK cell killing rate was detected.ELISA was applied to detect the expression levels of IL-2,IFN-γ and TNF-α in various cell culture media.Results:Compared with the HGC-27 group,the cell survival rate,clone formation quantity,and PD-1 and PD-L1 expression levels in the QUE-L group,QUE-M group and QUE-H group were gradually decreased(P<0.05),while the cell apoptosis rate gradually increased(P<0.05).Moreover,the NK cell killing rate and the expression levels of IL-2,IFN-γ and TNF-α in the cell culture medium of the QUE-L co-culture group,QUE-M co-culture group,and QUE-H co-culture group gradually increased compared to the HGC-27 co-culture group(P<0.05).On the basis of high concentration QUE treatment of HGC-27 cells,overexpression of PD-1 reversed the trend of changes in the above indicators(P<0.05).Conclusion:QUE may inhibit immune escape of gastric cancer cells by down-regulating PD-1/PD-L1 signaling pathway.

To adapt to the immune environment and the stress of antimicrobial exposure,Klebsiella pneumoniae can evolve into resistance to multiple antimicrobial agents in the hosts.However,less attention has been paid to the genetic evolution in vivo from antimicrobial susceptibility to resistance.This paper reviews the adaptive evolu-tion of drug resistance and virulence of K.pneumoniae in patients in current clinical practice.The potential mecha-nisms of the evolution of resistance to carbapenems,ceftazidime-avibactam,tigecycline and colistin in human hosts were mainly summarized.

Objective:To investigate the effect of anterior cervical discectomy and fusion(ACDF)and cervical spine stability in patients with two-segment cervical spondylosis.Methods:The clinical data of 60 patients with two-level cervical spondylotic myelopathy in Anqing Municipal Hospital were analyzed retrospectively.They were divided into group A(30 cases)and group B(30 cases)according to the communication results between doctors and patients.The control group was given anterior cervical corpectomy and fusion(ACCF),and the observation group was given ACDF.The clinical effects(cervical brace protection time,hospital stay,operation time and intraoperative blood loss),postoperative pain degree[visual analogue score(VAS)],neurological function[Japanese Association of Orthopaedic Surgeons(JOA)],cervical spine function[cervical spine dysfunction index(NDI)],cervical spine stability(C3-6 segment Cobb angle,intervertebral height and cervical spine curvature)and complication rate were compared between the two groups.Results:There were no significant differences in cervical brace protection time,hospital stay and operation time between the two groups(P>0.05).The VAS score in ACDF group was lower than that in ACCF group at 1,3 and 6 months after operation(t=4.312,3.864 and 9.338,P<0.05).The JOA score was higher than that of ACCF group(t=6.482,6.366,5.059,P<0.05).The NDI score was lower than that of ACCF group(t=4.922,6.178,8.859,P<0.05).Six months after operation,the Cobb angle,intervertebral height and cervical curvature of cervical vertebra 3-6(C3-6)in ACDF group were higher than those in ACCF group.The difference was statistically significant(t=5.011,2.171 and 3.386,P<0.05).The incidence of complications between the two groups was not different(P>0.05).Conclusion:ACDF for two-segment cervical spondylosis can effectively improve cervical spine function and nerve function,reduce postoperative pain,and reduce intraoperative blood loss,which is safe and effective.

Temporomandibular joint (TMJ) diseases are common clinical conditions. The number of patients with TMJ diseases is large, and the etiology, epidemiology, disease spectrum, and treatment of the disease remain controversial and unknown. To understand and master the current situation of the occurrence, development and prevention of TMJ diseases, as well as to identify the patterns in etiology, incidence, drug sensitivity, and prognosis is crucial for alleviating patients′suffering.This will facilitate in-depth medical research, effective disease prevention measures, and the formulation of corresponding health policies. Cohort construction and research has an irreplaceable role in precise disease prevention and significant improvement in diagnosis and treatment levels. Large-scale cohort studies are needed to explore the relationship between potential risk factors and outcomes of TMJ diseases, and to observe disease prognoses through long-term follw-ups. The consensus aims to establish a standard conceptual frame work for a cohort study on patients with TMJ disease while providing ideas for cohort data standards to this condition. TMJ disease cohort data consists of both common data standards applicable to all specific disease cohorts as well as disease-specific data standards. Common data were available for each specific disease cohort. By integrating different cohort research resources, standard problems or study variables can be unified. Long-term follow-up can be performed using consistent definitions and criteria across different projects for better core data collection. It is hoped that this consensus will be facilitate the development cohort studies of TMJ diseases.

Objective:To analyze the effectiveness and safety of robot-assisted percutaneous endoscopic posterior/transforaminal lumbar interbody fusion (RPE-P/TLIF) in the treatment of lumbar spinal stenosis with instability.Methods:From September 2018 to April 2022, 26 patients with lumbar spinal stenosis combined with lumbar segmental instability were treated with RPE-P/TLIF at the Department of Minimally Invasive Spine Surgery, Guangdong Provincial Hospital of Chinese Medicine. There were 13 males and 13 females, with a mean age of 57.92±7.09 years (range, 44 to 75 years) and a mean body mass index of 24.05±2.64 kg/m 2 (range, 19.38 to 29.06 kg/m 2). A total of 31 segments were included, including 21 cases of single-segment surgery (L 3, 4 in 2 cases, L 4, 5 in 18 cases, and L 5S 1 in 1 case) and 5 cases of two-segment surgery (all L 3-L 5). Before surgery and at 1, 6, and 12 months after surgery, as well as at the final follow-up, the visual analogue scale (VAS) was used to assess back pain and lower limb pain, and the Oswestry disability index (ODI) was used to evaluate spinal nerve function. Clinical efficacy was evaluated using the MacNab criteria at the final follow-up. Imaging evaluation indicators included pre- and post-operative intervertebral space height, lumbar lordosis angle, fusion rate, and accuracy of pedicle screw placement. Results:The follow-up time for the 26 patients was 42.88±10.09 months (range, 12 to 55 months). The mean operation time was 156.54±33.50 min, and the mean postoperative drainage volume was 27.23±20.20 ml. The VAS scores for back pain and lower limb pain before surgery were 4.35±1.23 and 6.08±0.63, respectively. These scores decreased to 2.08±0.69 and 1.85±0.54 at 1 month postoperatively, 1.85±0.54 and 0.77±0.59 at 6 months, 0.96±0.53 and 0.62±0.57 at 1 year, and 0.88±0.52 and 0.58±0.50 at the final follow-up, respectively. The differences were statistically significant ( F=85.943, P=0.001; F=547.946, P=0.014). The ODI scores before surgery and at 1, 6, 12 months after surgery, and at the final follow-up were 55.38%±5.89%, 28.38%±3.849%, 17.77%±2.67%, 12.58%±1.88% and 12.12%±2.27% respectively, with statistically significant differences ( F=783.289, P=0.010). According to the MacNab criteria, at the final follow-up, there were 18 cases of excellent, 6 cases of good, and 2 cases of fair, with an excellent and good rate of 92.3%. A total of 114 percutaneous pedicle screws were implanted with grades A, B and C being 109, 4 and 1, respectively. The preoperative, postoperative, and final follow-up intervertebral space heights were 10.55±1.96, 13.53±1.37, and 12.54±1.42 mm respectively, with statistically significant differences ( F=42.190, P<0.001). And the lumbar lordosis angles were 35.81°±10.80°, 35.69°±11.07°, and 36.08°±11.29° respectively, with no statistically significant differences ( P>0.05). At 12 months postoperatively, bone fusion was achieved in 25 cases, with a fusion rate of 96% (25/26). Conclusion:RPE-P/TLIF for lumbar spinal stenosis combined with lumbar instability were favorable. Being a safe and effective minimally invasive surgical option, it effectively enhanced the intervertebral space height in the surgical segment with fewer complications.

Objective:To develop a prediction model based on imaging features by contrast-enhanced MRI radiomics combined with clinical features for early recurrence of hepatocellular carcinoma (HCC) after radical resection.Methods:A retrospective study was carried out on 109 HCC patients who underwent radical resection at the Fifth Affiliated Hospital of Wenzhou Medical University from January 2015 to December 2020. Of 109 patients enrolled in this study, there were 96 males and 13 females, aged (58.3±10.7) years. Based on whether there was recurrence within 12 months after operation, the patients were divided into the early recurrence group ( n=31) and the control group ( n=78). These 109 patients were then randomly divided into the validation set ( n=23) and the training set ( n=86) at a ratio of 1∶4. Based on preoperative multi-phase contrast-enhanced MRI scanning, the tumor lesions were delineated on the Radcloud platform, and 1 409 quantitative radiomic features were extracted. Dimension reduction and screening of these features were carried out using variance threshold, SelectKBest and LASSO. Combined with clinical features (alpha fetoprotein, tumor size), several prediction model were established through machine learning. The predictive efficiencies of these models were evaluated using the area under the receiver operating characteristic (ROC) curve, accuracy rate, recall rate and balanced F score. Results:The proportions of irregular tumor shape and unclear tumor boundary, as well as maximum tumor diameter in the early recurrence group were significantly higher than that in the control group, but the proportion of pseudocapsule was significantly lower than that in the control group (all P<0.05). A total of 465 features were screened from the 1 409 features using the variance threshold method, followed by 38 features were screened using the method of SelectKBest. Finally 7 optimal radiomic features were screened based on the LASSO method. When combined with clinical features, 5 prediction models were established through machine learning. These models were support vector machine, Gaussian naive bayes, logistic regression, Multinomial naive bayes and K-nearest neighbor (KNN), respectively. Among these 5 models, the prediction efficiency of the KNN model was relatively highest, with the area under the ROC curve, accuracy rate, recall rate and balanced F score being 0.90, 0.98, 0.74 and 0.84 in the training set, and 0.76, 0.92, 0.75 and 0.83 in the verification set, respectively. Thus, the KNN model was selected as the best prediction model in this study. Conclusion:The prediction model of KNN was developed for early recurrence of HCC after radical resection based on preoperative contrast-enhanced MRI radiomics combined with clinical features.