BACKGROUND: Insufficient amount of periodontal soft tissue always brings red-and-white aesthetic problems of natural teeth and restorations, leads to gingivitis and peri-implant inflammation. Cell scaffold complexes with different cell and material combinations can promote periodontal soft tissue regeneration, which is expected to replace autogenous grafts. OBJECTIVE: To review the research progress and breakthrough in the application of autologous or allogeneic fibroblasts, keratinocytes, and mesenchymal stem cells in periodontal soft tissue increment. METHODS: Literature retrieval was conducted in PubMed, CNKI, Wanfang, Sciencedirect, and Medline databases. The key words were “gingival recession, soft tissue augmentation, root coverage, subepithelial connective graft” in English and Chinese. Abstracts were read; conclusions were preliminarily screened; and studies and experiments unrelated to the topic of this paper were excluded. Finally, 61 articles were included for result analysis. RESULTS AND CONCLUSION: Mesenchymal stem cells show great potential in gingival papilla increment. Transplanting only fibroblasts or keratinocytes combined with collagen, chitosan, acellular dermal matrix and other scaffolds in soft tissue could not achieve the expected keratinized gingival increment. Although the combination of two kinds of cells and collagen matrix showed more optimistic results and the current scaffold materials had good plasticity and biocompatibility, co-culture of fibroblasts and keratinocytes is time-consuming and expensive, and the conformation of scaffold material is relatively single. How to solve these problems will be a long process.

Objective To assess the expression level of targeting drug-based molecular biomarkers in ovarian clear cell carcinoma(OCCC)tissues and its clinical significance.Methods A total of 63 OCCC patients included 40 primary OCCC and 23 recurrent OCCC for secondary cytoreductive surgery(SCS),who had received primary surgeries at Fudan University Shanghai Cancer Center between January, 2008 and December, 2015 were enrolled, and immunohistochemistry SP method was used to test human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor-2 (HER2), aurora kinase A (AURKA), breast cancer susceptibility gene 1 (BRCA1), BRCA2 and programmed death-ligand 1 (PD-L1) protein expression in paraffin-embedded tissues. Results The positive rates of EGFR, HER2, AURKA, BRCA1,BRCA2 and PD-L1 in primary and recurrent tumor tissues were respectively 20%(8/40)vs 30%(7/23),22%(9/40)vs 35%(8/23),38%(15/40)vs 35%(8/23),42%(17/40)vs 39%(9/23),20%(8/40)vs 22%(5/23), 25%(10/40)vs 17%(4/23), and there were no significant differences between primary and recurrent OCCC (all P>0.05). χ2-test or Fisher exact analysis revealed that HER2 expression in recurrent tumor tissues had a relationship with chemoresistance (P<0.05), while the expression of other biomarkers showed no significant relationship with chemoresistance (all P>0.05). Further, Kaplan-Meier survival analysis showed that patients with HER2 and AURKA-positive expression had a significantly shorter progression-free survival time in primary OCCC(4 months vs 10 months,log-rank test,P<0.05 for HER2;and 4 months vs 10 months,P<0.05 for AURKA);and a shorter overall survival time after SCS in recurrent OCCC (10 months vs 44 months, P<0.05 for HER2;and 13 months vs 43 months, P<0.05 for AURKA). However,multivariate Cox proportional hazards regression analysis indicated that none of these 6 biomarkers was independent risk factor of progression-free survival time of primary OCCC or overall survival time after SCS for recurrent OCCC (P>0.05). Conclusion HER2 and AURKA could serve as prognostic factors in ovarian clear cell carcinoma.

Objective:To evaluate the relationship between preoperative SARS-CoV-2 vaccination and postoperative delirium(POD) in the patients.Methods:A total of 938 participants of either sex, aged 50-90 yr, weighing 50-90 kg, of American Society of Anesthesiologists Physical Status classificationⅠorⅡ, with preoperative Mini-Mental State Examination score ≥24, without communication barriers, undergoing elective knee or hip joint replacement under combined spinal-epidural anesthesia from June 2020 to June 2022 in Qingdao Municipal Hospital, were enrolled. The vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was recorded. The cerebrospinal fluid 2 ml was extracted after the puncture needle was successfully inserted into the subarachnoid space for determination of the concentrations of Aβ42, total tau protein (t-tau), and phosphorylated tau protein (p-tau) by enzyme-linked immunosorbent assay (by enzyme-linked immunosorbent assay). The Aβ42/t-tau and Aβ42/p-tau ratios were calculated. POD was assessed using the Confusion Assessment Method twice a day within 7 days after surgery or before discharge.The patients were divided into POD group and non-POD group according to whether they developed POD. The risk factors of which P values were less than 0.20 in the univariate logistic regression would enter the multivariate logistic regression analysis to investigate the relationship between SARS-CoV-2 vaccine and level of cerebral spinal fluid (CSF) biomarkers and POD. Results:Eight hundred and seventy-four patients were finally enrolled in the analysis, of which 169 patients developed POD, with an incidence of 19.3%.The results of logistic regression showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation, preoperative concentrations of Aβ42 in CSF, and increase in Aβ42/t-tau and Aβ42/p-tau ratios were protective factors for POD, and preoperative elevated concentrations of t-tau and p-tau in CSF were risk factors for POD ( P<0.05). After gender, age, preoperative Mini-Mental State Examination score, years of education, history of drinking, hypertension, diabetes mellitus and coronary heart disease were added to eliminate the influence of confounding factors, the results still showed that vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation was a protective factor for POD. Conclusions:Vaccination with SARS-CoV-2 inactivated vaccine within 6 months before operation is a protective factor for POD in patients.

Objective The aim of this study was to investigate the relationship between STAT1,STAT3 gene promoter CpG island methylation status and prognosis of patients with colorectal cancer(CRC)and the prognostic factors of CRC patients. Methods The cohort study was conducted to biosamples and follow up 239 patients with primary colorectal cancer pathologically diagnosed in Cancer Hospital of Harbin Medical University(Tumor Hospital). The methylation status of STAT1,STAT3 gene promoter CpG island was analyzed by methylation specific high-resolution melting curve(MS-HRM). Results The survival rates of 239 patients with colorectal cancer at 1 year,3 years and 5 years were 94. 90% ,86. 00% and 67. 20% ,respectively. The methylation status of STAT1 and STAT3 genes was not associated with postoperative survival in colorectal cancer patients( STAT1:HR=0. 85,95% CI:0. 55 ~1. 30,P=0. 44;STAT3:HR=0. 75,95% CI:0. 36~1. 58,P=0. 45). Dukes stage(HR=1. 31,95% CI:1. 14~1. 51,P<0. 01)and intraoperative intestinal stapler use(HR=1. 98,95% CI:1. 25 ~3. 14,P<0. 01) were important factors affecting the prognosis of colorectal cancer patients. The risk of death in patients with stage D and Dukes was significantly higher than that in stages A and B (HR=1. 31,95% CI:1. 14~1. 51,P<0. 01). Intestinal anastomosis was used during operation. The patient′s prognosis was better than that of patients without an intestinal stapler. However,gender,age,tumor location,gross tumor type,histological classification and postoperative chemotherapy were not associated with the prognosis of colorectal cancer. Conclusion Dukes stage is an independent factor affecting the prognosis of colorectal cancer. The prognosis of patients with intestinal stapler is better than that of non-users. The methylation status of STAT1 and STAT3 in peripheral blood is not a biomarkers for the prognosis of patients with colorectal cancer.

Objective:To evaluate the relationship between preoperative estimated glomerular filtration rate (eGFR) and postoperative delirium (POD) in the patients.Methods:Six hundred and twenty-five patients, aged ≥60 yr, of American Society of Anesthesiologists Physical Status classification Ⅰ-Ⅱ, scheduled for elective total knee and hip arthroplasty under combined spinal-epidural anesthesia, were included. Peripheral blood samples were collected before surgery, and serum creatinine levels were measured by the sarcosine oxidase method, and eGFR was calculated using the MDRD equation. After successful spinal-epidural puncture, cerebrospinal fluid 2 ml was collected for determination of β-amyloid 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group (NPOD group) according to the occurrence of POD. The logistic regression analysis was used to identify the risk factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic (ROC) curve was drawn to evaluate the accuracy of eGFR and biomarkers in predicting POD.Results:A total of 514 patients were finally enrolled in this study, and the incidence of POD was 16.7%. The logistic regression analysis showed that decreased eGFR and increased levels of P-tau and T-tau in CSF were risk factors for POD, while increased CSF Aβ42 level, Aβ42/P-tau ratio and Aβ42/T-tau ratio were protective factors for POD after adjusting for multiple confounding variables ( P<0.05). Analysis of mediating effet: The direct effect of eGFR on POD was -0.0 005 267, the total effect was 0.0 046 446, T-tau had a partly mediating role and the mediating effect accounted for 11.3% of the total effect. The area under the ROC curve of eGFR and CSF biomarker in predicting POD was 0.812( P<0.001). Conclusions:Preoperative decrease in eGFR is a risk factor for POD, and T-tau in CSF serves as a key mediator in the relationship between eGFR and POD.

Objective:To evaluate the relationship between preoperative serum albumin concentrations and postoperative delirium (POD) in the patients undergoing total knee/hip arthroplasty.Methods:Five hundred patients of both sexes, aged 50-90 yr, with body mass index of 50-80 kg, of American Society of Anesthesiologists Physical Status classification Ⅰ or Ⅱ, undergoing elective total knee or hip replacement under combined spinal-epidural anesthesia in our hospital from December 2021 to December 2022, were selected. Cerebrospinal fluid (CSF) samples were collected after successful subarachnoid puncture for determination of amyloid-beta 42 (Aβ42), total tau protein (T-tau) and phosphorylated tau protein (P-tau) concentrations using enzyme-linked immunosorbent assay. Confusion Assessment Method and Memorial Delirium Assessment Scale were used to evaluate the occurrence and severity of POD at 1-7 days after surgery (or before discharge), and the patients were divided into POD group and non-POD group (NPOD group). Logistic regression analysis was used to identify the risk factors for POD. The accuracy of plasma albumin concentration and CSF biomarker concentration in predicting POD was evaluated by the receiver operating characteristic (ROC) curve, and the mediating effect of CSF biomarker was analyzed.Results:A total of 343 patients were finally enrolled in the study, and the incidence of POD was 23.3%. There were statistically significant differences in age, preoperative plasma albumin concentration and Memorial Delirium Assessment Scale score in POD group as compared with NPOD group ( P<0.05). Before and after adjusting for confounding factors, decreased plasma albumin and increased concentrations of P-tau and T-tau in CSF before operation were the risk factors for POD, and increased concentrations of Aβ42, Aβ42/P-tau and Aβ42/T-tau ratio in CSF were protective factors for POD. The area under the ROC curve of preoperative plasma albumin concentrations in predicting POD was 0.668, and the area under the ROC curve of preoperative plasma albumin concentrations combined with CSF biomarker concentrations in predicting POD was 0.810 ( P<0.05). The direct effect of plasma albumin on POD was -0.009 869 2, the total effect was 0.029 443 7, and the mediating effect of P-tau accounted for 33.53% of the total effect. Conclusions:Decreased preoperative plasma albumin concentration is a risk factor for POD, and P-Tau in CSF serves as a key mediator in the relationship between serum albumin concentrations and postoperative delirium in the patients undergoing total knee/hip arthroplasty.

Objective:To evaluate the relationship between preoperative serum cystatin C (Cys C) concentration and postoperative delirium (POD) in the patients.Methods:Three hundred and ninety patients, aged >50 yr, of American Society of Anesthesiologists Physical Status classification Ⅰor Ⅱ, scheduled for elective knee and hip replacement under combined spinal-epidural anesthesia, with Mini-Mental State Examination scores >23 at 1 day before operation, were included in the study. Peripheral blood samples were collected before operation, and the serum Cys C concentration was measured by the latex-enhanced immunoturbidimetric assay. The cerebrospinal fluid (CSF) 2 ml was collected after successful spinal-epidural puncture for determination of amyloid-β 42 (Aβ42), total tau (T-tau) and phosphorylated tau (P-tau) concentrations by enzyme-linked immunosorbent assay. The patients were divided into POD group and non-POD group according to whether POD occurred. The logistic regression analysis was used to identify the risk and protective factors for POD, and the mediating effect of CSF biomarkers was analyzed. The receiver operating characteristic curve was drawn to evaluate the accuracy of serum Cys C concentration and combination of serum Cys C conceatration and CSF biomarker concentration in predicting POD.Results:Three hundred and twenty-seven patients were finally enrolled, and the incidence of POD was 13.5%. The results of logistic regression showed that increased serum Cys C concentration and increased concentrations of P-tau and T-tau in CSF were risk factors for POD, while increased concentration of Aβ42 and increased Aβ42/P-tau ratio and Aβ42/T-tau ratio in CSF were protective factors for POD ( P<0.05) after adjusting for multiple confounding variables such as age, sex, years of education, Mini-Mental State Examination score, smoking history, drinking history, hypertension and diabetes history. The mediation analysis showed that the relationship between serum Cys C concentration and POD was mediated by T-tau concentration in CSF (11.1%) and by Aβ42/T-tau ratio in CSF (18.0%). The area under the receiver operating characteristic curve of serum Cys C and CSF biomarker concentrations in predicting POD was 0.807 ( P<0.001). Conclusions:Increase in preoperative serum Cys C concentration is a risk factor for POD. T-tau concentration and Aβ42/T-tau ratio in CSF serve as the key mediators in the relationship between preoperative serum Cys C concentration and POD.

Objective:To evaluate the relationship between preoperative serum bilirubin concentrations and postoperative delirium (POD) in the patients undergoing knee or hip replacement.Methods:Medical records from 413 patients undergoing knee or hip arthroplasty were selected from August 2020 to October 2023 at Qingdao Municipal Hospital using a nested case-control design based on the PNDABLE study cohort. The patients were divided into POD group ( n=77) and non-POD group ( n=336) according to whether POD occurred. Univariate analysis was used to analyze the influencing factors. Logistic regression was used to identify the risk factors for POD. The significance of mediation effect was tested. The receiver operating characteristic curve was drawn to evaluate the accuracy of risk factors in predicting POD. Results:There were significant differences in age, education time, ratio of diabetes history, Memorial Delirium Assessment Scale score, total bilirubin concentration, direct bilirubin concentration, indirect bilirubin concentration, Aβ 42 concentration, p-tau concentration, t-tau concentration, Aβ 42/p-tau ratio and Aβ 42/t-tau ratio between POD group and non-POD group ( P<0.05). The results of logistic regression analysis showed that preoperative serum total bilirubin, direct bilirubin and indirect bilirubin were risk factors for POD ( P<0.05). The results of mediation effects showed that the concentration of total tau protein in CSF partly mediated the relationship between high serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and POD. The area under the receiver operating characteristic curve of total bilirubin, direct bilirubin and indirect bilirubin combined with CSF biomarker concentrations in predicting POD was 0.83 ( P<0.001). Conclusions:Preoperative elevated concentrations of total bilirubin, direct bilirubin and indirect bilirubin are risk factors for POD in the patients undergoing knee or hip replacement. CSF t-tau concentration has a partly mediating role in the association between serum total bilirubin, direct bilirubin and indirect bilirubin concentrations and the development of POD.

Objective:To evaluate the relationship between hippocampal macrophage polarization and perioperative neurocognitive disorders in mice with tibial fractures.Methods:Forty-five clean-grade healthy male C57/BL6 mice, aged 5-7 months, were divided into 3 groups ( n=15 each) using the random number table method: control group (group C), anesthesia group (group A) and anesthesia surgery group (group AS). Group C received no treatment. Group A was anesthetized with isoflurane inhaled for 15 min. In AS group, intramedullary nail fixation of tibial fracture was performed under anesthesia through inhalation of 2% isoflurane. Morris water maze test and open field test were performed before anesthesia/on 1 day before surgery and after anesthesia/on 1, 3 and 7 days after operation. Five mice were randomly selected after the behavioral experiments were completed at each time point, and hippocampal tissues were taken after the animals were sacrificed for determination of the expression of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6, chemokine (c-c motif) ligand 12 (CCL2), CCL5, CCL8, iNOS and Arg-1 mRNA (by quantitative real-time polymerase chain reaction), expression of iNOS and Arg-1 proteins (by Western blot), and percentage of CD11b, CD45, CD86 and CD206 cells in hippcampal area (by immunofluorescence staining). Results:Compared with group C, the escape latency was significantly prolonged after operation, the number of crossing the platform was reduced after operation, the expression of TNF-ɑ, IL-6, CCL5 and CCL8 mRNA and iNOS protein and mRNA was up-regulated, the expression of Arg-1 protein and mRNA was down-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells in the hippocampus were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05), and no significant change was found in the parameters mentioned above in group A ( P>0.05). Compared with group A, the escape latency was significantly prolonged after surgery, the frequency of crossing the platform was reduced after surgery, the expression of iNOS mRNA was up-regulated, the percentages of CD11b + CD45 + cells and CD11b + CD86 + cells were increased, and the percentages of CD11b + CD206 + cells were decreased in AS group ( P<0.05). Conclusions:The occurrence of PND may be related to increased polarization to M1 macrophages in the hippocampus and decreased polarization to M2 macrophages in mice with tibial fracture, which further leads to central inflammatory responses.