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 retrospectively analyze the clinical characteristics, co-mutated genes in newly diagnosed acute myeloid leukemia (AML) patients with NRAS and KRAS gene mutations, and the impact of NRAS and KRAS mutations on prognosis. METHODS: The clinical data and next-generation sequencing results of 80 newly diagnosed AML patients treated at our hospital from December 2018 to December 2023 were collected. The clinical characteristics, co-mutated genes of NRAS and KRAS , and the impact of NRAS and KRAS mutations on prognosis in newly diagnosed AML patients were analyzed. RESULTS: Among 80 newly diagnosed AML patients, NRAS mutations were detected in 20 cases(25.0%), and KRAS mutations were detected in 9 cases(11.3%). NRAS mutations predominantly occurred at codons 12 and 13 of exon 2, as well as codon 61 of exon 3, while KRAS mutations were most commonly occurred at codons 12 and 13 of exon 2, all of which were missense mutations. There were no statistically significant differences observed in terms of age, sex, white blood cell count(WBC), hemoglobin(Hb), platelet count(PLT), bone marrow blasts, first induction chemotherapy regimen, CR1/CRi1 rates, chromosome karyotype, 2022 ELN risk classification and allogeneic hematopoietic stem cell transplantation(allo-HSCT) among the NRAS mutation group, KRAS mutation group and NRAS/KRAS wild-type group (P >0.05). KRAS mutations were significantly correlated with PTPN11 mutations (r =0.344), whereas no genes significantly associated with NRAS mutations were found. Survival analysis showed that compared to the NRAS/KRAS wild-type group, patients with NRAS mutation had a relatively higher 5-year overall survival (OS) rate and relapse-free survival (RFS) rate, though the differences were not statistically significant (P =0.097, P =0.249). Compared to the NRAS/KRAS wild-type group, patients with KRAS mutation had a lower 5-year OS rate and RFS rate, with no significant differences observed (P =0.275, P =0.442). There was no significant difference in the 5-year RFS rate between the KRAS mutation group and NRAS mutation group (P =0.157), but the 5-year OS rate of patients with KRAS mutation was significantly lower than that of patients with NRAS mutation (P =0.037). CONCLUSION In newly diagnosed AML patients, KRAS mutation was significantly correlated with PTPN11 mutation. Compared to patients with NRAS/KRAS wild-type, those with NRAS mutation showed a more favorable prognosis, while patients with KRAS mutation showed a poorer prognosis; however, these differences did not reach statistical significance. Notably, the prognosis of AML patients with KRAS mutation was significantly inferior compared to those with NRAS mutation.
Humans ; Leukemia, Myeloid, Acute/diagnosis* ; Mutation ; Prognosis ; Proto-Oncogene Proteins p21(ras)/genetics* ; GTP Phosphohydrolases/genetics* ; Retrospective Studies ; Membrane Proteins/genetics* ; Female ; Male ; Middle Aged ; Adult ; Aged

This study investigates the pharmacokinetics and metabolic characteristics of three marine-derived piericidins as potential drug leads for kidney disease: piericidin A (PA) and its two glycosides (GPAs), glucopiericidin A (GPA) and 13-hydroxyglucopiericidin A (13-OH-GPA). The research aims to facilitate lead selection and optimization for developing a viable preclinical candidate. Rapid absorption of PA and GPAs in mice was observed, characterized by short half-lives and low bioavailability. Glycosides and hydroxyl groups significantly enhanced the absorption rate (13-OH-GPA > GPA > PA). PA and GPAs exhibited metabolic instability in liver microsomes due to Cytochrome P450 enzymes (CYPs) and uridine diphosphoglucuronosyl transferases (UGTs). Glucuronidation emerged as the primary metabolic pathway, with UGT1A7, UGT1A8, UGT1A9, and UGT1A10 demonstrating high elimination rates (30%-70%) for PA and GPAs. This rapid glucuronidation may contribute to the low bioavailability of GPAs. Despite its low bioavailability (2.69%), 13-OH-GPA showed higher kidney distribution (19.8%) compared to PA (10.0%) and GPA (7.3%), suggesting enhanced biological efficacy in kidney diseases. Modifying the C-13 hydroxyl group appears to be a promising approach to improve bioavailability. In conclusion, this study provides valuable metabolic insights for the development and optimization of marine-derived piericidins as potential drug leads for kidney disease.
Animals ; Male ; Mice ; Aquatic Organisms/chemistry* ; Biological Availability ; Cytochrome P-450 Enzyme System/metabolism* ; Glucuronosyltransferase/metabolism* ; Microsomes, Liver/metabolism* ; Molecular Structure ; Biological Products/pharmacokinetics* ; Pyridines/pharmacokinetics*

The efficient production of L-glutamate is dependent on the product's rapid efflux, hence researchers have recently concentrated on artificially modifying its transport system and cell membrane wall structure. Considering the unique composition and structure of the cell wall of Corynebacterium glutamicum, we investigated the effects of CmpLs on L-glutamate synthesis and transport in SCgGC7, a constitutive L-glutamate efflux strain. First, the knockout strains of CmpLs were constructed, and it was confirmed that the deletion of CmpL1 and CmpL4 significantly improved the performance of L-glutamate producers. Next, temperature-sensitive L-glutamate fermentation with the CmpL1 and CmpL4 knockout strains were carried out in 5 L bioreactors, where the knockout strains showcased temperature-sensitive characteristics and enhanced capacities for L-glutamate production under high temperatures. Notably, the CmpL1 knockout strain outperformed the control strain in terms of L-glutamate production, showing production and yield increases of 69.2% and 55.3%, respectively. Finally, the intracellular and extracellular metabolites collected at the end of the fermentation process were analyzed. The modification of CmpLs greatly improved the L-glutamate excretion and metabolic flux for both L-glutamate production and transport. Additionally, the CmpL1 knockout strain showed decreased accumulation of downstream metabolites of L-glutamate and intermediate metabolites of tricarboxylic acid (TCA) cycle, which were consistent with its high L-glutamate biosynthesis capacity. In addition to offering an ideal target for improving the stability and performance of the industrial strains for L-glutamate production, the functional complementarity and redundancy of CmpLs provide a novel target and method for improving the transport of other metabolites by modification of the cell membrane and cell wall structures in C. glutamicum.
Corynebacterium glutamicum/genetics* ; Glutamic Acid/biosynthesis* ; Fermentation ; Metabolic Engineering ; Bacterial Proteins/metabolism* ; Bioreactors/microbiology* ; Gene Knockout Techniques

AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P＜0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P＜0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P＜0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P＜0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.05,P＜0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.05,P＜0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.

Objective:To evaluate the efficacy of gadolinium ethoxybenzyl- diethy-lenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI features in the preoperative prediction of tertiary lymphoid structures (TLS) within hepatocellular carcinoma (HCC) lesions.Methods:This retrospective cross-sectional study included clinical and pathological data from 297 HCC patients treated at the Southwest Hospital, Army Medical University between June 2021 and November 2022. Based on postoperative pathology, patients were categorized into TLS-negative ( n=93) and TLS-positive ( n=204) groups. MRI features of HCC lesions using Gd-EOB-DTPA enhancement and relevant clinical data were analyzed. Intergroup comparisons of imaging features and laboratory findings were performed using independent sample t-test, Mann-Whitney U test, χ2 test, or Fisher exact test, as appropriate. The logistic regression analysis was conducted to identify independent predictors of TLS positivity. A predictive model was constructed and visualized using a nomogram. The model′s predictive performance and clinical utility were assessed using the receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). The area under the ROC curve (AUC) was compared using the DeLong test. Results:Significant differences were observed between the TLS-negative and TLS-positive groups in alpha-fetoprotein (AFP) levels, intratumoral hemorrhage, and peritumoral satellite nodules in the hepatobiliary phase ( P<0.05). Multivariate logistic regression identified intratumoral hemorrhage ( OR=0.123, 95% CI 0.070-0.216, P<0.001) and peritumoral satellite nodules in the hepatobiliary phase ( OR=0.236, 95% CI 0.093-0.596, P=0.002) as independent predictive factors for TLS-positivity. The imaging model based on these two features yielded an AUC of 0.764 (95% CI 0.709-0.809) for predicting TLS-positivity. When combined with AFP levels, the resulting clinical-imaging model achieved a superior AUC of 0.784 (95% CI 0.732-0.829), which was significantly higher than that of the imaging model alone ( Z=2.20, P=0.028). A nomogram was constructed based on the clinical-imaging model. The calibration curve demonstrated good predictive performance of the nomogram, and the DCA showed that the curve remained above the default line across a range of reasonable threshold probabilities, indicating that patients could derive clinical benefit. Conclusion:A nomogram model based on Gd-EOB-DTPA enhanced MRI features combined with AFP levels can effectively predict the presence of TLS in HCC.

Purpose To explore the predictive value of CT-enhanced for tumor mutation burden(TMB)in hepatocellular carcinoma(HCC).Materials and Methods A total of 22 patients with pathologically confirmed HCC after undergoing radical resection in the First Affiliated Hospital,Army Medical University(Third Military Medical University)from January 2020 to January 2023 were collected,all of whom were quantified for TMB.Clinical,laboratory tests,CT imaging characteristics and follow-up of patients were recorded.Variables with P<0.2 were screened by stepwise regression analysis for independent risk factors for TMB.The area under the curve of receiver operating characteristic was used to assess the diagnostic efficacy.Results High TMB level was a risk factor for disease-free survival after HCC surgery(HR=1.115,P<0.05).According to the optimal cut-off value,TMB was classified into a high-risk group(>9.25 mutation/Mb)and low-risk group(≤9.25 mutation/Mb).Univariate analysis of intratumor ischemia or necrosis was statistically different between the high-risk and low-risk groups(P=0.005),and only intratumor ischemia or necrosis was an independent risk factor for predicting high TMB level by stepwise regression analysis(P<0.05).The area under the curve for predicting disease-free survival was 0.833(95%CI 0.615-0.956,P<0.001),with a sensitivity of 100.0%and a specificity of 66.7%.Conclusion High TMB level is associated with poor prognosis after HCC resection.Intratumor ischemia or necrosis have certain clinical value in predicting high TMB level,and are expected to provide a reference basis for personalized diagnosis and treatment of HCC patients.

Medical ultrasound technology is widely used for diagnosis and therapy in clinical practice.Ultrasound probes,which are directly contact with patients,pose a potential risk of pathogen transmission.This expert consen-sus was developed by a multidisciplinary team based on international guidelines,standards in China,and the results of a national survey,aiming to reduce the risk of healthcare-associated infection through standardizing reprocessing of medical ultrasound probes,and formulating consensus recommendations with the Delphi method.The consensus clarifies the reprocessing principles for three types of ultrasound probes of different infection risks:external-use ul-trasound probes,interventional percutaneous ultrasound probes,and internal-use ultrasound probes,puts forward systematic suggestions on the reprocessing standards and disinfection levels of ultrasound probe isolation covers and coupling agents,the reprocessing procedures and methods of ultrasound probes,as well as architectural layout and management of reprocessing,so as to provide a scientific prevention and control framework for ensuring ultrasound diagnosis and therapy safety.

This study was aimed at understanding the prevalence and influencing factors of food-borne parasitic diseases in ethnic minority areas of Guizhou Province,to provide a scientific basis for the development of appropriate intervention measures based on the human-animal-environment One Health concept.In 2023,the infection status of the human population,reservoir hosts,intermediate hosts,food-borne parasitic diseases,and related social and environmental factors were investigated in Congjiang County in Qidongnan Miao and Dong Autonomous Prefecture;Luodian County in Qiannan Buyi and Miao Autonomous Prefecture;and Ceheng County in Qianxinan Buyi and Miao Autonomous Prefecture.At least 1 000 individuals were sampled from each county,along with at least 50 insect-protected host samples from each location.Food-borne parasite infections were detected with the modified Kato thick smear method.A questionnaire survey was administered to the population.Detection of food-borne parasitic metacercariae was performed in intermediate host fish through the flaking and digestion method,and in crabs through the pounding and sedimentation method.The chi-square test was used to compare rates,and logistic regression was applied for multivariate analysis.A total of 3 023 questionnaires and fecal samples were collected.Males accounted for 47.50%,females accounted for 52.50%,and members of ethnic minorities accounted for 96.06%.A total of 186 food-borne parasitic infections were identified,and the infection rate was 6.15%.Five insect species were detected,which showed an infection rate of 5.39%.The infection rate of Clonorchis sinensis was 0.33%,that of Taenia was 0.40%,that of Heteroceles was 0.17%,that of Acanthus was 0.17%,and that of Echinostoma was 0.03%.Human infections with Echinostomus colloides and Echinostomia transferoris had not previously been reported in China.Single-factor analysis revealed statistically significant differences in food-borne parasite infections according to various factors,including the consumption of untreated water,raw fish and shrimp,raw pig blood,raw cow gastric juice,and raw pork and beef,as well as raw pig and cow viscera(P<0.05).Multivariate analysis indicated that the risk factors for food-borne parasite infections among residents in minority areas of Guizhou Province included the consumption of raw pig blood(OR=2.841,95%CI:1.809-4.463),raw cow gastric juice(OR=2.122,95%CI:1.297-3.469),and raw fish and shrimp(OR=1.779,95%CI:1.049-3.018).A total of 173 fecal samples of the reservoir host were examined,which showed a rate of food-borne parasite infection of 5.2%.A total of 510 intermediate host fish were examined,which showed a 4.51%positivity rate of encysted metacercaria of Clonorchis sinensis.The crab,pig,and beef samples were not positive.In conclusion,food-borne parasitic infections were prevalent in ethnic minority regions of Guizhou Province,and consumption of raw food were influencing factors.A focus on populations with raw food consumption habits,including raw pig blood,cow gastric juice,fish and shrimp,is essential.Concurrently,monitoring of animal hosts must be strengthened to perform key interventions according to the One Health concept.

Objective:To investigation the situation of water improvement projects in villages affected by drinking water-type endemic fluorosis in Qinghai Province and the prevalence of dental fluorosis among children, in order to provide a basis for consolidating the achievements in prevention and control of drinking water-type endemic fluorosis and adjusting prevention and control measures.Methods:The monitoring data on drinking water-type endemic fluorosis were collected from the disease prevention and control centers in various counties of Qinghai Province from 2021 to 2023, the situation of water improvement projects, the fluorine content of domestic drinking water and the prevalence of dental fluorosis in children aged 8 to 12 years old were retrospectively analyzed.Results:From 2021 to 2023, the numbers of villages affected by drinking water-type endemic fluorosis in Qinghai Province were 338, 335, and 328, respectively. The numbers of water improvement projects were 125, 127 and 124, respectively. The normal operation rates were 100%, 100% and 99.19% (123/124), respectively. The qualified rates of water fluoride level were 100%, 99.21% (126/127) and 99.19% (123/124), respectively. The detection rates of dental fluorosis among children aged 8 to 12 were 4.34% (515/11 877), 5.70% (646/11 331) and 4.48% (490/10 943), respectively. There was a statistically significant difference in the detection rate of dental fluorosis among children in different years (χ 2 = 22.79, P < 0.001). Conclusions:The overall operation status of water improvement project in villages affected by drinking water-type endemic fluorosis in Qinghai Province is generally good, but there has been some relaxation in management and maintenance in the later stage, and there is a phenomenon of project intermittency. The detection rate of dental fluorosis among children aged 8 to 12 remains low, and endemic fluorosis caused by drinking water is under continuous control.