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

ObjectiveTo identify key factors influencing cognitive function in the elderly, including traditional Chinese medicine (TCM) constitutional classification, and to rank their relative importance.MethodsWe used cross-sectional data from seven geographical regions across mainland China. The Changsha version of the Montreal Cognitive Assessment was used to assess cognitive function. A “least absolute shrinkage and selection operator” (LASSO) model, multivariate linear regression analysis, and random forest (RF) model were used. Subgroup analyses were performed to examine the correlation between key TCM constitution types and cognitive function in different population subgroups.ResultsA total of 24 803 individuals aged 60 and above were included in the study. We selected 18 influential factors using the LASSO model. Higher education, being married, and having insurance were positively correlated with cognitive function in the elderly (all P .05). In contrast, poor sleep, vision impairment, hearing impairment, basic activities of daily living disability, instrumental activities of daily living disability, depression, hypertension, coronary heart disease, diabetes, stroke, yang-deficiency constitution (YADC), yin-deficiency constitution (YIDC), qi deficiency constitution (QDC), and blood stasis constitution (BSC) were negatively correlated with cognitive function (all P .05). YIDC and BSC affected all dimensions of cognitive function (all P .05). YADC mainly affected attention, language, abstraction (verbal analogies), memory, and orientation to time and place dimensions (P .001). QDC mainly affected language and abstraction (verbal analogies) dimensions (P .05). The negative correlations between BSC, YADC, YIDC, and QDC scores and cognitive function revealed statistically significant differences across most subgroups. The RF model identified education, BSC, and poor sleep quality as the three most influential factors in our study.ConclusionBSC, YADC, YIDC, and QDC were associated with cognitive decline in the elderly. Our findings provide new perspectives and significant references for interventions for early-stage cognitive disorders.

The standardized workflow of computer-aided static guided implant surgery includes preoperative exami-nation,data acquisition,guide design,guide fabrication and surgery.Errors may occur at each step,leading to irrevers-ible cumulative effects and thus impacting the accuracy of implant placement.However,clinicians tend to focus on fac-tors causing errors in surgical operations,ignoring the possibility of irreversible errors in nonstandard guided surgery.Based on the clinical practice of domestic experts and research progress at home and abroad,this paper summarizes the sources of errors in guided implant surgery from the perspectives of preoperative inspection,data collection,guide de-signing and manufacturing and describes strategies to resolve errors so as to gain expert consensus.Consensus recom-mendation:1.Preoperative considerations:the appropriate implant guide type should be selected according to the pa-tient's oral condition before surgery,and a retaining screw-assisted support guide should be selected if necessary.2.Da-ta acquisition should be standardized as much as possible,including beam CT and extraoral scanning.CBCT performed with the patient's head fixed and with a small field of view is recommended.For patients with metal prostheses inside the mouth,a registration marker guide should be used,and the ambient temperature and light of the external oral scan-ner should be reasonably controlled.3.Optimization of computer-aided design:it is recommended to select a handle-guided planting system and a closed metal sleeve and to register images by overlapping markers.Properly designing the retaining screws,extending the support structure of the guide plate and increasing the length of the guide section are methods to feasibly reduce the incidence of surgical errors.4.Improving computer-aided production:it is also crucial to set the best printing parameters according to different printing technologies and to choose the most appropriate postpro-cessing procedures.

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.

Objective: To study the effect of p-phenylenediamine (PPD) on liver and kidney function in occupational exposed workers. Methods: Workers in a hair dye production enterprise which used p-phenylenediamine as a raw material for production were selected as the main research population. Then we conducted a questionnaire survey on the basic conditions of workers and conducted occupational health checkups on general health status, liver and kidney function. Occupational health examination assessment results were tested in Taizhou Cancer Hospital. All data was built using EpiData 3.1 software, and statistical analysis was performed using software SPSS 20.0. Results: The liver function indicators including direct bilirubin, prealbumin, total protein, and white protein, globulin, aspartate aminotransferase, glutamyl transpeptidase, and total bilirubin in the workers exposed to high concentration of PPD were at high normal values, and these indicators were significantly different from low PPD concentration group (P<0.05) . The serum creatinine and serum uric acid in the renal function index were significantly higher in workers exposed to PPD than in workers exposed to low concentrations and in the control group (P<0.05) . Conclusion Occupational exposed to PPD may have a hazard to the workers’ liver and kidney function. Long-term occupational exposure to PPD may lead to increased cumulative exposure of workers, which may cause potential chronic liver and kidney damage in occupationally exposed populations.

OBJECTIVETo evaluate the antioxidant effects of Taohong Siwu decoction and to exploit the bioactive constituents.

METHODThe samples were prepared by macroporous adsorptive resins (TH-1-TH-15). Three antioxidant models were adopted to evaluate the antioxidant activities of Taohong Siwu decoction and its different separated fractions in vitro. It was found that fractions (TH-2, TH-4, TH-7, TH-8, TH-9), separated from Taohong Siwu decoction, mainly contributed to the antioxidant effects. The chemical constituents in the most active fraction TH-8 were identified and determined by HPLC.

RESULTTH-8 showed significant antioxidant activities in the antioxidant experiments. Six compounds in the fraction were determined which were amygdalin, albiflorin, paeoniflorin, benzoic acid, coumaric acid and ferulic acid. The contents were 75.70, 31.26, 60.79, 1.196, 1.108, 4.861 mg L(-1), respectively.

CONCLUSIONGlycosides and aromatic acids may be the principle effective constituents in the active fraction.

Antioxidants ; chemistry ; Drugs, Chinese Herbal ; chemistry

OBJECTIVETo investigate Siwu decoction and its composite drugs on the blood-deficiency model mice induced by acetylphenyhydrazine and cyclophosphamide.

METHODAcetylphenyhydrazine and cyclophosphamide were used to copy the blood-deficiency model mice. Automatic hematology analyzer was used to test the peripheral hemogram. Weighting method was used to test the liver index and spleen index; Kits for ATPase test was used to test the activities of Na+ - K+ - ATPase/Ca2+ - Mg2+ - ATPase in erythrocyte membrane. Flow cytometry was used to test the bone marrow cells' cell cycle.

RESULTAngelicar Sinensis Radix and Paeoniae Radix Alba had the most effective activity on the peripheral hemogram. Paeoniae Radix Alba, the drug pair including Angelicar Sinensis Radix and the drug- group including Paeoniae Radix Alba had the most effective activity on the liver index. All the drugs, drug-pairs, drug-groups and the formula had effect on the spleen index. To the activity of Na+ - K+ - ATPase in erythrocyte membrane, Rehmanniae Radix Praeparata, the drug-pairs and drug-groups including Angelicar Sinensis Radix exhibited the most effective activity. All the drugs, drug-pairs, drug-groups and the formula had the protective effect on the damaged bone marrow cells.

CONCLUSIONSiwu decoction and its composite drugs all had effect on the blood-deficiency model mice, but the action intensity was different. Angelicar Sinensis Radix and Paeoniae Radix Alba exhibited the most effective activity to the protection of the blood-deficiency model mice.

Adenosine Triphosphatases ; drug effects ; metabolism ; Angelica sinensis ; Animals ; Bone Marrow Cells ; drug effects ; metabolism ; pathology ; Cell Cycle ; drug effects ; Cyclophosphamide ; Disease Models, Animal ; Drugs, Chinese Herbal ; metabolism ; pharmacology ; Female ; Glucosephosphate Dehydrogenase Deficiency ; chemically induced ; drug therapy ; metabolism ; pathology ; Liver ; drug effects ; metabolism ; Mice ; Mice, Inbred ICR ; Paeonia ; Phenylhydrazines ; Protective Agents ; pharmacology ; Spleen ; drug effects ; metabolism

The formulae decoctions are commonly used in clinic and have characteristics of simple preparation and rapid effect. It was considered as a complex physical and chemical system. In this article, the physical and chemical properties and chemical components and their relationships were investigated to explore the changes of characteristics resulted from different combinations of drugs of Shaofu Zhuyu decoction. The method of partial leasts-quares regression was adopted to evaluate the correlation between physical and chemical parameters and chemical components. These researches may provide a new way to investigate the state of bioactive components, the action mechanisms, and property of treating diseases of traditional Chinese medicine decoction.
Chemistry, Pharmaceutical ; Drug Combinations ; Drugs, Chinese Herbal ; chemistry