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 value of albumin-bilirubin （ALBI）， easy albumin-bilirubin （EZ-ALBI）， and platelet-albumin-bilirubin （PALBI） scores in predicting 2-year survival in patients with HCV-associated hepatocellular carcinoma （HCV-HCC）. MethodsA retrospective analysis was performed for the clinical data of 174 patients with HCV-HCC who were admitted to The Third People’s Hospital of Kunming from January 2020 to January 2022， and the patients were followed up till 2 years after admission. According to the follow-up results， the patients were divided into survival group with 95 patients and death group with 79 patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the influencing factors for the survival of HCV-HCC patients. The Kaplan-Meier method was used to plot survival curves and analyze the 2-year survival rate of HCV-HCC patients with different EZ-ALBI grades， and the log-rank test was used for comparison between groups. ResultsThere were significant differences between the survival group and the death group in platelet count， aspartate aminotransferase （AST）， total bilirubin， albumin （Alb）， alpha-fetoprotein （AFP）， prealbumin， prothrombin time， international normalized ratio， PALBI score， ALBI score， EZ-ALBI score， Model for End-Stage Liver Disease （MELD） score， HCV genotype， peritoneal effusion， and vascular invasion （all P<0.05）. The univariate Cox regression analysis showed that AST， Alb， AFP， ALBI score， EZ-ALBI score， PALBI score， MELD score， Barcelona Clinic Liver Cancer Staging， and peritoneal effusion were influencing factors for the survival of patients （all P<0.05）， and the multivariate Cox regression analysis showed that EZ-ALBI score （hazard ratio ［HR］=1.850， 95% confidence interval ［CI］： 1.054 — 3.247， P=0.032） and peritoneal effusion （HR=1.993， 95%CI： 1.030 — 3.858， P=0.041） were independent risk factors for the survival of HCV-HCC patients. The survival curve analysis showed that the patients with EZ-ALBI grade 1/2/3 had a 2-year survival rate of 90.9%， 60.2%， and 32.2%， respectively， and there was a significant difference in cumulative survival rate between the patients with different EZ-ALBI grades （χ²=26.294， P<0.001）. ConclusionEZ-ALBI score and the presence or absence of peritoneal effusion can be used as predictors of the survival of HCV-HCC patients.

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 establish the precise management model for the centralized preparation of cytotoxic drugs in pharmacy intravenous admixture services （PIVAS）， and evaluate the effects of its application. METHODS Pharmacists in PIVAS established the precise management model by soliciting clinical opinions and consulting literature on the centralized preparation of cytotoxic drugs and continuously refining every step of the preparation of cytotoxic drugs， based on data feedback from the information closed-loop management system and the limit of stability time of finished solutions. The indicators such as the preparation time， delivery time， the storage time of finished infusion solutions after preparation， and the completion rate of infusion within the stability time limit were analyzed before the implementation （January to December 2023） and after the implementation （January to December 2024） of this model， to evaluate its application effectiveness. RESULTS The overall framework for the precise management model included upgrading the functions of the prescription review system， improving the prescription review database， providing specialized training for PIVAS pharmacists， managing dynamic batch decision for drug preparation， managing special drugs， managing finished infusion distribution， and establishing a continuous improvement mechanism. Compared with before implementation， the average preparation time of the second and third batches of cytotoxic drugs with more concentrated morning preparation tasks in this model was significantly shorter than before implementation （P＜0.05）； the delivery time of finished infusion after implementation （[ 11.49±2.92） min] was significantly shorter than the delivery time before implementation （[ 22.11±5.03） min] （P＜0.001）； the storage time of some drugs with shorter stable time limit and carboplatin in combination regimens （paclitaxel or docetaxel+carboplatin） was significantly shortened compared to before implementation （P＜0.05）， and the completion rate of infusion within the stability time limit was significantly improved compared to before implementation （P＜0.05）. CONCLUSIONS Our hospital has successfully established a precise management model for the centralized preparation of cytotoxic drugs in PIVAS. This mode can significantly shorten the preparation time of each batch of PIVAS in the morning， make batch decisions more reasonable and improve the infusion completion rate within the stable time limit of the finished product.

By systematically combing ancient and modern literature， this paper examined Tribuli Fructus and Astragali Complanati Semen（ACS） used in the famous classical formulas from the aspects of name， origin， production area， harvesting and processing， clinical efficacy， so as to provide a basis for the development of famous classical formulas containing such medicinal materials. The results showed that the names of Tribuli Fructus in the past dynasties were mostly derived from its morphology， and there were nicknames such as Baijili， Cijili and Dujili. The name of ACS in the past dynasties were mostly originated from its production areas， and there were nicknames such as Baijili， Shayuan Jili and Tongjili. Because both of them had the name of Baijili， confusion began to appear in the Song dynasty. In ancient and modern times， the main origin of Tribuli Fructus were Tribulus terrestris， and ancient literature recorded the genuine producing areas of Tribuli Fructus was Dali in Shaanxi and Tianshui in Gansu， but today it is mainly cultivated in Anhui and Shandong. The fruit is the medicinal part， harvested in autumn throughout history. There is no description of the quality of Tribuli Fructus in ancient times， and the plump， firm texture， grayish-white color is the best in modern times. Traditional processing methods for Tribuli Fructus included stir-frying and wine processing， while modern commonly used is purified， fried and salt-processed. The ancient records of Tribuli Fructus were spicy， bitter， and warm in nature， with modern research adding that it is slightly toxic. The main effects of ancient and modern times include treating wind disorders， improving vision， promoting muscle growth， and treating vitiligo. The mainstream base of ACS used throughout history is Astragalus complanatus. Ancient texts indicated ACS primarily originated from Shaanxi province. Today， the finest varieties come from Tongguan and Dali in Shaanxi. The medicinal part is the seed， traditionally harvested in autumn. Modern harvesting occurs in late autumn or early winter， followed by sun-drying. Ancient texts valued seeds with a fragrant aroma as superior， while modern standards prioritize plump， uniform and free of impurities. Traditional processing methods for ACS included frying until blackened and wine-frying， while modern practice commonly employs purification methods. In terms of medicinal properties， the ancient and modern records are sweet and warm in nature. Due to originally classified under Tribuli Fructus， its effects were thus regarded as equivalent to those of Tribuli Fructus， serving as the medicine for treating wind disorders， additional functions included tonifying the kidneys and treating vitiligo. The present record of its efficacy is to tonify the kidney and promote Yang， solidify sperm and reduce urine， nourish the liver and brighten the eye， etc. Based on the textual research results， it is suggested that when developing the famous classical formulas of Tribuli Fructus medicinal materials， we should pay attention to the specific reference object of Baijili， T. terrestris and A. complanatus should be identified and selected， and the processing method should be in accordance with the requirements of the formulas.

ObjectiveTo investigate the therapeutic efficacy， influencing factors， and safety of a treatment regimen based on coblopasvir hydrochloride capsules/sofosbuvir tablets in patients with chronic hepatitis C virus （HCV） infection in a real-world setting. MethodsA total of 253 patients who attended The Third People’s Hospital of Kunming from September 1， 2021 to May 31， 2024 were enrolled， among whom there were 86 patients with compensated liver cirrhosis （CLC group） and 167 patients with chronic hepatitis C （CHC group）. The patients were treated with coblopasvir hydrochloride capsules （60 mg）/sofosbuvir tablets （400 mg） with or without ribavirin tablets for 12 weeks， and they were followed up for 12 weeks after drug withdrawal. The primary outcome measures were the rate of sustained virologic response at week 12 after treatment （SVR12） and safety， and the secondary outcome measures were the changes in liver function， renal function， blood routine， and liver stiffness measurements （LSM） after 4 weeks of treatment， after 12 weeks of treatment， and at 12 weeks after drug withdrawal. The independent-samples t test and the Mann-Whitney U test were used for comparison of continuous data between two groups， and the Friedman test was used for comparison between multiple groups， while the Bonferroni method was used for paired comparison within each group； the chi-square test was used for comparison of categorical data between two groups. The Logistic analysis was used to investigate related influencing factors. ResultsThe 253 patients with chronic HCV infection had a mean age of 49.38±8.65 years， and there were 151 male patients （59.7%）. Of all patients， 33.99% （86/253） had liver cirrhosis， 25.69% （65/253） had hypertension， 10.67% （27/253） had HIV infection， 8.70% （22/253） had diabetes， 3.95% （10/253） had liver cancer， 1.98% （5/253） had chronic hepatitis B， and 7.91% （20/253） were treatment-experienced patients. As for genotype distribution， 2.77% （7/253） had genotype 1， 12.65% （32/253） had genotype 2， 66.01% （167/253） had genotype 3， 16.60% （42/253） had genotype 6， and 1.98% （5/253） had unknown genotype. The patients had an overall SVR12 rate of 92.09%， with an SVR12 rate of 93.02% in the CLC group and 91.02% in the CHC group. The multivariate logistic regression analysis showed that age （odds ratio ［OR］=1.086， 95% confidence interval ［CI］： 1.007 — 1.170， P=0.032） and HCC （OR=9.178， 95%CI： 1.722 — 48.912， P=0.009） were independent influencing factors for sustained virologic response. Compared with baseline data， the CLC group had significant reductions in alanine aminotransferase （ALT） （χ²=107.103， P0.05）， aspartate aminotransferase （AST） （χ²=90.602， P0.05）， and LSM （χ²=42.235， P0.05） after 12 weeks of treatment， while the CHC group had significant reductions in total bilirubin （χ²=15.113， P0.05）， ALT （χ²=202.237， P0.05）， AST （χ²=161.193， P0.05）， and LSM （χ²=37.606， P0.05）. The incidence rate of serious adverse events was 1.58%， and none of the patients withdrew from drug therapy； the patients with such events were relieved after active symptomatic treatment. The incidence rate of all adverse events was 23.72%， among which fatigue （17.39%） and nausea （2.37%） were the most common adverse events， and these events often disappeared within 2 weeks or were gradually relieved after symptomatic treatment. ConclusionCoblopasvir hydrochloride capsules/sofosbuvir tablets with or without ribavirin tablets has good efficacy and safety in the treatment of chronic HCV infection.

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