Liver transplantation (LT) has become a standard treatment for end-stage liver diseases, and graft injury is intricately associated with poor prognosis. Granzyme B (GZMB) plays a vital role in natural killer (NK) cell biology, but whether NK-derived GZMB affects graft injury remains elusive. Through the analysis of single-cell RNA-sequencing data obtained from human LT grafts and the isolation of lymphocytes from mouse livers following ischemia-reperfusion injury (IRI), we demonstrated that 2NK cells with high expression of GZMB are enriched in patients and mice. Both systemically and liver-targeted depletion of NK cells led to a notable reduction in GZMB⁺ cell infiltration, subsequently resulting in diminished graft injury. Notably, the reconstitution of Il2rg ^-/- Rag2 ^-/- mice with purified Gzmb-KO NK cells demonstrated superior outcomes compared to those with wild-type NK cells. Crucially, global knockout of GZMB and pharmacological inhibition exhibited remarkable improvements in liver function in both mouse IRI and rat LT models. Moreover, a phosphorylated derivative of FDA-approved vidarabine was identified as an effective inhibitor of mouse GZMB activity by molecular dynamics, which could provide a potential avenue for therapeutic intervention. Therefore, targeting NK cell-derived GZMB during the LT process suggests potential therapeutic strategies to improve post-transplant outcomes.

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

Objective To study the effective fraction and mechanism of Lycium barbarum leaves on improving learning and memory ability of subacute aging mice induced by D-galactose injection.Methods The model of subacute aging mice was developed by injection of D-galactose subcutaneously,and different extracts of Lycium barbarum leaves were prepared.The effects of the extracts of Lycium barbarum leaves on the learning and memory ability of model mice were evaluated by Y maze experiment and new object recognition experiment.The pathomorphological changes of hippocampus in mice were observed by hematoxylin-eosin and Nissl staining.The levels of brain-derived neurotrophic factor(BDNF),nerve growth factor(NGF),glial cell line-derived neurotrophic factor(GDNF),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),interferon-γ(IFN-γ)and interleukin-10(IL-10)in hippocampus of mice were detected by enzyme-linked immunosorbent assay.The activities of superoxide dismutase(SOD)and the contents of glutathione(GSH)and malondialdehyde(MDA)in hippocampus of mice were detected by related assay kits.Detection of apoptosis in the hippocampal region of mouse brain tissue using the TUNEL method.Western blotting analysis was used to detect the expressions of antioxidant proteins Nrf2,HO-1 and apoptotic proteins Caspase-3,Caspase-9 in hippocampus of mice.Results The water extraction part and 80%alcohol precipitation supernatant part of Lycium barbarum leaves significantly improved the learning and memory ability of model mice,improved the pathological damage of hippocampus in mice,increased the number of Nissl bodies in hippocampus of mice,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF,and promoted the expression of neurotrophic factors BDNF,NGF and GDNF.Pro-inflammatory factors TNF-α,IL-1β and IFN-γ expression declines while anti-inflammatory factor IL-10 expression rises.The activity of SOD and the expression of GSH were increased,and the expression of MDA was decreased.Increase the expression of Nrf2 and HO-1 antioxidant proteins;reduce the expression of Caspase-3 and Caspase-9 apoptosis pathway proteins.Inhibition of apoptosis in the hippocampal region of mouse brain tissue using a model.Conclusion The water extracts and 80%alcohol precipitation supernatant extracts of Lycium barbarum leaves are the effective fractions of Lycium barbarum leaves to improve the learning and memory ability of D-galactose-induced subacute aging mice,and its mechanism might be related to the inhibition of neuronal apoptosis caused by oxidative stress and inflammation.

Objective To improve the clinical recognition of anti-leucine-rich glioma inactivated-1(LGI1)antibody associated encephalitis through investigating the clinical characteristics of the disease,so as to improve diagnosis and prognosis.Methods A total of 31 consecutive patients with anti-LGI1 antibody associated encephalitis were recruited during January 2020 to March 2022 in Brain Hospital Affiliated to Nanjing Medical University including their clinical manifestations.Patients were divided into first-line immunotherapy group and mycophenolate mofetil(MMF)adding-on group according to the initial treatment regimen.Univariate and multivariate COX regression analysis were used to analyze the factors of the recurrence of anti-LGI1 antibody encephalitis.mRS was used to evaluate the prognosis.Results Seizure(93.5%),memory defect(80.6%)and psychosis(58.1%)were the most common manifestations in 31 patients.Fourteen patients suffered with hyponatremia,1 patients with elevated white cells and 17 patients with elevated proteins in CSF.The corresponding positive rates of anti-LGI1 antibody were 90.3%and 93.1%in serum and CSF.Fourteen patients had abnormal cranial MR.All patients received first-line immunotherapy,with 13 patients followed by MMF.Eleven patients were recurred in the follow-up.Univariate COX regression analysis found female(HR =3.85,95%CI:1.12-13.24,P =0.032),MMF adding-on therapy(HR = 4.03,95%CI:1.07-15.22,P = 0.04)were associated with relapse.However no independent associations were found after multivariate COX regression analysis.Twenty-two patients had sequeleas during follow-up,with memory decline as the most common symptom.All patients achieved good prognosis.Conclusions Anti-LGI1 antibody associated encephalitis may have good prognosis,but relapse is not rare.The majority patients have sequelaes,with memory defect and psychosis being the most common symptoms.MMF might have no prevention effect on anti-LGI1 antibody encephalitis recurrence.

Objective:Early identification of ischemic stroke patients with large vessel occlusion can improve referral efficiency and shorten reperfusion time. The purpose of this study was to analyze the characteristics of patients with large vessel occlusion and identify factors that could predict large vessel occlusion.Methods:The clinical data of 432 patients with ischemic stroke treated through emergency green channel were retrospectively analyzed, and the differences between the large vessel occlusion group (LVO group) and the non-large vessel occlusion group (non-LVO group) were compared, and two independent risk factors of the LVO group were screened out by logistics regression analysis: baseline NIHSS score and D-dimer value. The predicted cutoff values of NIHSS score and D-dimer were further determined by the receiver operating characteristic (ROC) curve.Results:A total of 432 patients with ischemic stroke had complete imaging data, with a mean age of 68.5±12.4 years, including 275 (63.7%) males, and 245 (56.7%) in the LVO group and 187 (43.3%) in the non-LVO group. Age, hemorrhagic transformation, thrombolytic therapy, endovascular treatment, atrial fibrillation, baseline NIHSS score [14.0 (6.0-20.0) vs. 3.0 (1.0-6.0), P<0.05], and D-dimer value at admission [0.9(0.4-2.3) mg/L vs. 0.3 (0.2-0.5)mg/L, P<0.05] were statistically significant different between the two groups. Multivariate Logistic regression analysis showed that higher baseline NIHSS score( OR=1.22,95% CI: 1.17-1.27)and higher D-dimer value( OR=3.10,95% CI: 2.14-4.47)were independent risk factors for large vessel occlusion. Baseline NIHSS score combined with D-dimer value was a good predictor of large vessel occlusion(AUC 0.85 [0.81-0.89]). ROC curve suggested that NIHSS score >6.5 and D-dimer >0.57 mg/L were the cutoff values for predicting large vessel occlusion. Conclusions:Higher baseline NIHSS score and D-dimer value are valuable for early prediction of large vessel occlusion, patients with NIHSS score >6.5 points and D-dimer >0.57 mg/L should be promptly transported to an advanced stroke center for treatment.

Objective:To investigate the status of cancer-related fatigue in lung cancer patients and its related influencing factors, thus to provide reference for clinical active intervention and improve the quality of life of patients.Methods:In this study, interviews and questionnaires were used to collect patient-related data.Seventy patients with lung cancer from January 2016 to January 2019 in Zhuji People's Hospital were selected in this study, and relevant information was collected and analyzed.The relevant influencing factors of cancer-related fatigue was analyzed.Results:The survey showed that the average score of cancer-related fatigue in lung cancer patients was (5.71±1.96)points, which was in moderate status, the behavioral dimension fatigue score was (5.95±2.38)points, the emotional dimension score was (5.48±2.37)points, the sensory dimension score was (5.46±2.38)points, and the cognitive/emotional dimension score was (4.79±2.11)points.Age, serum albumin level, surgery and anemia were the influencing factors of cancer-induced fatigue in patients with lung cancer( P<0.05). Sleep disorders, anxiety, depression were positively correlated with cancer-induced fatigue in patients with lung cancer( r=0.642, 0.350, 0.192, P=0.000, 0.000, 0.000). The average quality of life score of lung cancer patients was (84.14±6.52)points, which was negatively correlated with cancer-induced fatigue and functional areas, and positively correlated with symptom areas, insomnia and diarrhea( P<0.05). Conclusion:The cancer-induced fatigue of 70 patients with lung cancer in Zhuji People's Hospital is in moderate status, and the main influencing factors are age, serum albumin, surgery and anemia.The survey can provide a reference for subsequent clinical intervention for lung cancer patients.

Objective:To systematically review the therapeutic effect of continuous high positive end-expiratory pressure (PEEP) ventilation in patients with non-acute lung injury/acute respiratory distress syndrome (non-ALI/ARDS) under general anesthesia mechanical ventilation in the intensive care unit (ICU).Methods:PubMed, JBI Evidence-based Nursing Center Library, Cochrane Library, Embase, Medline, Wanfang Date, CNKI and VIP Database were searched for randomized controlled trials (RCT) and clinical controlled trials (CCT) using different levels of PEEP for the treatment of patients (uncombined ALI/ARDS) in ICU. The search period was from January 1st, 1990 to November 30th, 2018. Compared with the control group, the experimental group was treated with relatively high levels of PEEP ventilation. Outcome indicators were hospital mortality or 28-day mortality, partial oxygen pressure, and incidence of ARDS, atelectasis, and lung infections, etc. The RevMan 5.3 software was used for Meta-analysis.Results:Twelve articles were included, all of which were RCT studies; with 2 Chinese articles and 10 English articles. Meta-analysis showd that there was no statistically significant difference in the effect of different levels of PEEP on the mortality of patients [hospital mortality: odds ratio ( OR) = 1.06, 95% confidence interval (95% CI) was 0.57 to 1.96, P = 0.85; 28-day mortality: OR = 0.34, 95% CI was 0.09 to 1.32, P = 0.12]. Compared with low PEEP, persistently high PEEP could increase the patient's partial oxygen pressure [weighted mean difference ( WMD) = 48.27, 95% CI was 22.56 to 73.97, P = 0.000 2], prevent the occurrence of ARDS ( OR = 0.32, 95% CI was 0.13 to 0.82, P = 0.02), and decrease the incidence of lung infection ( OR = 0.52, 95% CI was 0.30 to 0.89, P = 0.02), but there was no significant difference in the incidence of atelectasis between the two groups ( OR = 0.69, 95% CI was 0.23 to 2.06, P = 0.51). Conclusion:In the treatment of patients in ICU with non-ALI/ARDS under general anesthesia mechanical ventilation, using relatively high levels of PEEP (10-16 cmH 2O, 1 cmH 2O = 0.098 kPa) instead of low levels of PEEP (≤8 cmH 2O) can significantly increase the partial oxygen pressure and significantly reduce the incidences of ARDS and lung infection.

Objective To explore the feasibility of 3D printed individualized applicator for the intracavitary HDR-brachytherapy for nasopharyngeal carcinoma.Methods CT scan was performed in 1 case of recurrent rT1 nasopharyngeal carcinoma and 1 case of T2 residual nasopharyngeal carcinoma and the obtained images were transmitted to 3D image processing software.The geometric contour parameters of the nasopharyngeal cavity were obtained and a pipeline was designed to make it close to the recurrent gross tumor volume (rGTV).Individualized cavity applicators were created by using 3D printer.The applicator was inserted into the patient's nasopharyngeal cavity through oral cavity.The source tube and false source were inserted into the preset pipe of the applicator.CT scan was performed again and the images were transmitted to the 3D brachytherapy planning system.Mter delineating the target volume and organ at risk,treatment plan was optimized.After completing the first treatment,the applicator was removed.Before second treatment in a few days,CT scan was reviewed to confirm whether the position was correct.Results When the applicator was inserted into the nasopharyngeal cavity,it could be fully aligned with the nasopharyngeal wall and self-fixed without additional fixation measures.Comparing the location of false source in multiple reviews of CT scan,the error was ≤ 1 mm.No significant discomfort was reported throughout the treatment.In optimized three-dimensional treatment,100％ prescription dose curve included the full rGTV,maximum dose of the brain stem and spinal cord was＜30％ prescription dose.Recurrent patients were given with a prescription dose of DT 40Gy/8 fractions/4 weeks and patients with residual tumors were given with 12Gy/2 fractions/1 week.No tumor recurrence was observed at postoperative 3 months in two cases.Conclusions The 3D printed individualized nasopharyngeal intracavitary applicator has the advantages of self-fixation,accurate location,good repeatability and good patient tolerance.The short-term outcome is effective,whereas its long-term clinical effect and adverse reactions need to be further observed.

Objective: Comparing the benefit of Abidor, lopinavir/ritonavir and recombinant interferon α-2b triple combination antiviral therapy and lopinavir/ritonavir and interferon dual combination antiviral therapy to hospitalized novel coronavirus pneumonia 2019 in Zhejiang province. Methods: A multi-center prospective study was carried out to compare the effect of triple combination antiviral therapy with dual combination antiviral therapy in 15 medical institutions of Zhejiang Province. All patients were treated with recombinant interferon α-2b (5 million U, 2 times/d) aerosol inhalation. 196 patients were treated with abidol (200 mg, 3 times/d) + lopinavir / ritonavir (2 tablets, 1 time/12 h) as the triple combination antiviral treatment group. 41 patients were treated with lopinavir / ritonavir (2 tablets, 1 time/12 h) as the dual combination antiviral treatment group. The patients who received triple combination antiviral therapy were divided into three groups: within 48 hours, 3-5 days and > 5 days after the symptom onset. To explore the therapeutic effects of triple combination antiviral drugs and dual combination antiviral drugs, as well as triple combination antiviral drugs with different antiviral initiate time. SPSS17.0 software was used to analyze the data. Results: The time of virus nucleic acid turning negative was (12.2 ± 4.7) days in the triple combination antiviral drug group, which was shorter than that in the dual combination antiviral drug group [(15.0 ± 5.0) days] (t = 6.159, P < 0.01 ). The length of hospital stay [12 (9, 17) d] in the triple combination antiviral drug group was also shorter than that in the dual combination antiviral drug group [15 (10, 18) d] (H = 2.073, P < 0.05). Comparing the antiviral treatment which was started within 48 hours, 3-5 days and > 5 days after the symptom onset of triple combination antiviral drug group, the time from the symptom onset to the negative of viral shedding was 13 (10,16.8), 17 (13,22) and 21 (18-24) days respectively (Z = 32.983, P < 0.01), and the time from antiviral therapy to the negative of viral shedding was (11.8±3.9) , (13.5±5.1) and (11.2±4.3) d. The differences among the three groups were statistically significant (Z=32.983 and 6.722, P<0.01 or<0.05). Conclusions The triple combination antiviral therapy of Abidor, Lopinavir/Litonavir and recombinant interferon α-2b showed shorter viral shedding time and hospitalization time compared with the dual combination antiviral therapy. The earlier the time to initiate triple antiviral treatment, the shorter the time of virus shedding.