The alternative pathway (AP) of the complement system is a key contributor to the pathogenesis of several diseases including paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), C3 glomerular disease (C3G) and age-related macular degeneration (AMD). Complement factor B (CFB) is a trypsin-like serine protein that circulates in the human bloodstream in a latent form. As a key node of the alternative pathway, it is an important target for the treatment of diseases mediated by the complement system. With the successful launch of iptacopan, the CFB small molecule inhibitors has become a current research hotspot, a number of domestic and foreign pharmaceutical companies are actively developing CFB small molecule inhibitors. In this paper, the research progress of CFB small molecule inhibitors in recent years is systematically summarized, the representative compounds and their activities are introduced according to structural types and design ideas, so as to provide reference and ideas for the subsequent research on CFB small molecule inhibitors.

ObjectiveTo investigate the value of noninvasive imaging detection （FibroScan）， two serological models of gamma-glutamyl transpeptidase-to-platelet ratio （GPR） score and S index， and two inflammatory factors of interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） in predicting liver fibrosis in patients with HBeAg-positive chronic hepatitis B （CHB）， as well as the consistency of liver biopsy in pathological staging， and to provide early warning for early intervention of CHB. MethodsA retrospective analysis was performed for 131 HBeAg-positive CHB patients who underwent liver biopsy in The Third People’s Hospital of Kunming from January 2019 to December 2023. The results of liver biopsy were collected from all patients， and related examinations were performed before liver biopsy， including total bilirubin， alanine aminotransferase， platelet count， gamma-glutamyl transpeptidase， albumin， IL-6， TNF-α， liver stiffness measurement （LSM）， and abdominal ultrasound. An analysis of variance was used for comparison of normally distributed continuous data between groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between groups； the chi-square test was used for comparison of categorical data between groups. A Kappa analysis was used to investigate the consistency between LSM noninvasive histological staging and pathological staging based on liver biopsy， and the Spearman analysis was used to investigate the correlation between each variable and FibroScan in the diagnosis of liver fibrosis stage. The Logistic regression analysis was used to construct joint predictive factors. The receiver operating characteristic （ROC） curve was used to evaluate the value of each indicator alone and the joint predictive model in the diagnosis of liver fibrosis， and the Delong test was used for comparison of the area under the ROC curve （AUC）. ResultsIn the consistency check， inflammation degree based on liver biopsy had a Kappa value of 0.807 （P<0.001）， and liver fibrosis degree based on liver biopsy had a Kappa value of 0.827 （P<0.001）， suggesting that FibroScan noninvasive histological staging and liver biopsy showed good consistency in assessing inflammation degree and liver fibrosis stage. Age was positively correlated with LSM， GPR score， S index， IL-6， and TNF-α （all P<0.05）， and GPR score， S index， IL-6， and TNF-α were positively correlated with LSM （all P<0.05）. GPR score， S index， IL-6， and TNF-α were all independent risk factors for diagnosing significant liver fibrosis （≥S2） and progressive liver fibrosis （≥S3） （all P<0.05）. As for each indicator alone， GPR score had the highest value in the diagnosis of significant liver fibrosis （≥S2）， followed by S index， IL-6， and TNF-α， while S index had the highest value in the diagnosis of progressive liver fibrosis （≥S3）， followed by GPR score， TNF-α， and IL-6. The joint model had a higher predictive value than each indicator alone （all P<0.05）. ConclusionThere is a good consistency between FibroScan noninvasive histological staging and pathological staging based on liver biopsy. GPR score， S index， IL-6， and TNF-α are independent risk factors for evaluating different degree of liver fibrosis in CHB， and the combined prediction model established by them can better diagnose liver fibrosis.

ObjectiveTo investigate the efficacy and safety of the direct-acting antiviral agents coblopasvir hydrochloride/sofosbuvir （CLP/SOF） regimen used alone or in combination with ribavirin （RBV） in the treatment of patients with genotype 3 hepatitis C virus （HCV） infection in terms of virologic response rate， liver function recovery， improvement in liver stiffness measurement （LSM）， and adverse drug reactions， and to provide a reference for clinical medication. MethodsA total of 98 patients with genotype 3 HCV infection who attended The Third People’s Hospital of Kunming from January 2022 to December 2023 were enrolled， and according to the treatment method， the patients were divided into CLP/SOF+RBV treatment group with 55 patients and CLP/SOF treatment group with 43 patients. The patients were observed in terms of rapid virologic response at week 4 （RVR4）， sustained virologic response （SVR）， previous treatment experience， underlying diseases， laboratory and imaging indicators， and adverse reactions during treatment. The course of treatment was 12 weeks， and the patients were followed up for 12 weeks after drug withdrawal. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the Friedman test was used for comparison within each group at different time points， and the Bonferroni method was used for further comparison and correction of P value； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. The univariate and multivariate Logistic regression analyses were used to investigate the influencing factors for SVR12. ResultsBefore treatment， there were significant differences between the CLP/SOF+RBV treatment group and the CLP/SOF treatment group in terms of LSM， total bilirubin （TBil）， gamma-glutamyl transpeptidase （GGT）， HCV genotype， and the presence or absence of liver cirrhosis and compensation （all P<0.05）. The 98 patients with genotype 3 HCV infection had an RVR4 rate of 81.6% and an SVR12 rate of 93.9%. The patients with genotype 3a HCV infection had an RVR4 rate of 84.44% and an SVR12 rate of 97.78%， while the patients with genotype 3b HCV infection had an RVR4 rate of 79.25% and an SVR12 rate of 90.57%. There were significant differences in RVR4 and SVR12 rates between the patients without hepatocellular carcinoma and those with hepatocellular carcinoma， there was a significant difference in RVR4 rate between the patients without HIV infection and those with HIV infection， and there was a significant difference in SVR12 rate between the previously untreated patients and the treatment-experienced patients （all P<0.05）. The univariate Logistic regression analysis showed that treatment history， hypertension， hepatocellular carcinoma， ascites， albumin （Alb）， and platelet count were influencing factors for SVR12 （all P<0.05）， and the multivariate Logistic regression analysis showed that hepatocellular carcinoma （odds ratio=0.034， 95% confidence interval： 0.002‍ ‍—‍‍ 0.666， P=0.026） was an independent influencing factor for SVR12. After treatment with CLP/SOF combined with RBV or CLP/SOF alone， the patients with genotype 3 HCV infection showed gradual reductions in the liver function parameters of TBil， GGT， and alanine aminotransferase （all P<0.05） and a gradual increase in the level of Alb （P<0.05）. As for renal function， there were no significant changes in blood urea nitrogen and creatinine after treatment （P>0.05）. For the patients with or without liver cirrhosis， there was a significant reduction in LSM from baseline after treatment for 12 weeks （P<0.05）. Among the 98 patients with genotype 3 HCV infection， 9 tested positive for HCV-RNA at 12 weeks after treatment， 2 showed no response during treatment， 4 showed virologic breakthrough， and 3 experienced recurrence. The overall incidence rate of adverse events during treatment was 17.35% for all patients. ConclusionCLP/SOF alone or in combination with RBV has a relatively high SVR rate in the treatment of genotype 3 HCV infection， with good tolerability and safety in patients during treatment， and therefore， it holds promise for clinical application.

OBJECTIVE: To explore the current research status and hotspots in the field of biomechanics of diabetic foot by bibliometric analysis methods. METHODS: Literatures related to biomechanics of diabetic foot published in the Web of Scienc Core Collection (WoSCC) from 1981 to 2024 were searched. CiteSpace software and R language bibliometrics plugin were used to conduct a visual analysis of annual publication volume of the literature, including publication volume of each country and region, the publication situation of authors and institutions, the citation situation of individual literature, and the co-occurrence network of keywords. RESULTS: Totally 996 literatures were included, and the number of published papers increased steadily. The United States (261 papers) and China (89 papers) were the top two countries in terms of the number of published papers. The mediating centrality of the United States was 0.94, and that of China was 0.01. Scholars such as Cavanagh and institutions like the Cleveland Clinic were at the core of research in this field. High-frequency keywords include plantar pressure (plantar pressure), diabetic foot (diabetic foot), ulceration (ulcer), etc. The research focuses on plantar pressure, ulcer formation and prevention, etc. CONCLUSION Biomechanical research on diabetic foot mainly focuses on the pressure distribution on the sole of the foot, callus formation, mechanical analysis of soft tissues on the sole of the foot, and the study of plantar decompression caused by Achilles tendon elongation. The research trend has gradually shifted from focusing on joint range of motion to gait and the design of braces and assistive devices, and has begun to pay attention to muscle strength, gait imbalance and proprioception abnormalities.
Humans ; Diabetic Foot/physiopathology* ; Biomechanical Phenomena ; Bibliometrics

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

There are huge differences between tumor cells and normal cells in material metabolism, and tumor cells mainly show increased anabolism, decreased catabolism, and imbalance in substance metabolism. These differences provide the necessary material basis for the growth and reproduction of tumor cells, and also provide important targets for the treatment of tumors. Ferroptosis is an iron-dependent form of cell death characterized by an imbalance of iron-dependent lipid peroxidation and lipid membrane antioxidant systems in cells, resulting in excessive accumulation of lipid peroxide, causing damage to lipid membrane structure and loss of function, and ultimately cell death. The regulation of ferroptosis involves a variety of metabolic pathways, including glucose metabolism, lipid metabolism, amino acid metabolism, nucleotide metabolism and iron metabolism. In order for tumor cells to grow rapidly, their metabolic needs are more vigorous than those of normal cells. Tumor cells are metabolically reprogrammed to meet their rapidly proliferating material and energy needs. Metabolic reprogramming is mainly manifested in glycolysis and enhancement of pentose phosphate pathway, enhanced glutamine metabolism, increased nucleic acid synthesis, and iron metabolism tends to retain more intracellular iron. Metabolic reprogramming is accompanied by the production of reactive oxygen species and the activation of the antioxidant system. The state of high oxidative stress makes tumor cells more susceptible to redox imbalances, causing intracellular lipid peroxidation, which ultimately leads to ferroptosis. Therefore, in-depth study of the molecular mechanism and metabolic basis of ferroptosis is conducive to the development of new therapies to induce ferroptosis in cancer treatment. Ferroptosis, as a regulated form of cell death, can induce ferroptosis in tumor cells by pharmacologically or genetically targeting the metabolism of substances in tumor cells, which has great potential value in tumor treatment. This article summarizes the effects of cellular metabolism on ferroptosis in order to find new targets for tumor treatment and provide new ideas for clinical treatment.

The prevalence of diabetes mellitus in China has recently been increasing year by year,and spontaneous skin ulcers in diabetic patients,as one of the most serious complications,often develop on the patient's extremities represented by foot ulcers.Due to the complexity and variety of its pathogenesis,it leads to poor clinical outcomes and difficulty in healing.Thus,pa-tients often face the risk of amputation and death.Therefore,the exploration of mechanisms of the vascular pathogenesis of diabetic delayed-healing wounds and targeted screening of therapeutic agents has become a current research hotspot.Herein,in this paper,we briefly review the role of impaired angiogenesis and vascular dysfunction in diabetic skin ulcers,and the research progress of classical hypoglycemic and natural compounds against vascular lesions is preliminarily summarized to provide a theoretical basis for effective clinical treatment.

Objective:To investigate the independent and combined effects of maternal smoking during pregnancy and offspring genetic susceptibility on overall cancer mortality.Methods:Based on the United Kingdom Biobank ( n=419 228) data, the Cox proportional hazard regression model was used to estimate the effect of maternal smoking during pregnancy on offspring overall cancer (including 16 cancers in men and 18 in women) mortality and its combined effect and interaction with offspring genetic factors. Results:Maternal smoking during pregnancy was significantly associated with a 13% increased risk of overall cancer mortality in men [hazard ratio( HR)=1.13, 95% CI: 1.06-1.20] and 19% increased risk in women ( HR=1.19, 95% CI: 1.11-1.27). Participants with high genetic risk had the highest overall cancer mortality than those with low genetic risk (men: HR=1.42, 95% CI: 1.30-1.55; women: HR=1.38, 95% CI: 1.25-1.52). Compared with participants without maternal smoking during pregnancy and low genetic risk, those with maternal smoking during pregnancy and high genetic risk were associated with a 56% increased risk of overall cancer mortality in men ( HR=1.56, 95% CI: 1.37-1.77) and 59% in women ( HR=1.59, 95% CI: 1.39-1.83). Conclusion:Maternal smoking during pregnancy may increase offspring overall cancer mortality and more severe harm in individuals with high genetic risk.

Objective:To elucidate the etiological and epidemiological characteristics and epidemiological patterns of viral acute respiratory infections (ARI) in Shanghai during 2023, with the aim of providing robust laboratory evidence for effective prevention and control strategies against related respiratory diseases and facilitating risk assessment.Methods:Respiratory pathogens were detected in the clinical surveillance specimens submitted by sentinel hospitals through multiplex PCR, as part of the multi-pathogen surveillance of acute respiratory infections in Shanghai during 2023. The obtained detection result were statistically analyzed in conjunction with sample information.Results:The positive detection rate of viral pathogens in 2023 was 21.17% (984/4 648), with rates of 33.53% (504/1 503) observed in ILI cases and 15.62% (480/3 145) in SARI cases. Influenza A virus (FluA) was the predominant virus detected, accounting for 13.7% (637/4 648). Other viruses identified in the surveillance samples included influenza B virus (Flu B), human rhinovirus/enterovirus (HRV/HEV), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), parainfluenza virus (PIV), adenovirus (ADV) and human bocavirus (HBoV). Regarding temporal distribution, HRV/HEV and RSV exhibited the highest detection rates during the second quarter at 2.27% each (28/1 236). PIV had its peak during the third quarter at a rate of 2.49% (35/1 405), and HMPV showed prevalence mainly during the third and fourth quarters, with detection rates of 2.63% (37/1 405) and 2.35% (32/1 360), respectively.Conclusions:In acute respiratory infection surveillance cases in Shanghai in 2023, Flu A emerged as the predominant respiratory pathogen. The detection rate of HMPV ranked second only to Flu A, while other respiratory viruses such as HRV/HEV, RSV, and PIV were detected during different seasons and co-circulated. The prevalence of various respiratory viruses varied among different infected populations and over times.