ObjectiveTo investigate the independent predictive factors for 90-day mortality in patients with acute-on-chronic liver failure （ACLF）， to establish a risk predictive model， and to assess its predictive efficacy in comparison with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ. MethodsA retrospective analysis was performed for the clinical data of 394 patients with ACLF who were admitted to The Affiliated Hospital of Inner Mongolia Medical University and Hohhot Second Hospital from July 2018 to July 2024， and general information and laboratory markers on admission were collected from all patients. The independent-samples t test or the Mann-Whitney U test was used for comparison of quantitative data between two groups， and the chi-square test or the adjusted chi-square test was used for comparison of qualitative data between two groups. The LASSO regression analysis was used to identify related variables， and the multivariate logistic regression analysis was used to establish a predictive model and generate a nomogram. The receiver operating characteristic （ROC） curve， the area under the ROC curve （AUC）， calibration curve， and clinical decision curve were used to assess the performance of the model. ResultsA total of 394 patients with ACLF were included in this study， with 136 patients in the training set， 58 in the internal validation set， and 200 in the external validation set. The cohort had a mean age of 52.9±11.7 years， among whom male patients accounted for 72.84% （287/394）， the patients with HBV infection accounted for 22.33% （88/394）， the patients with alcohol-related causes accounted for 45.94% （181/394）， and the patients with other causes （including drug-induced and autoimmune diseases） accounted for 31.73% （125/394）. The overall 90-day mortality rate was 27.41% （108/394）. The multivariate logistic regression analysis showed that diabetes （odds ratio ［OR］= 5.831， 95% confidence interval ［CI］： 1.587 — 21.424， P=0.008）， cystatin C （Cys-C） （OR=2.984， 95%CI： 1.501 — 5.933， P=0.002）， and spontaneous peritonitis （SBP） （OR=5.692， 95%CI： 2.150 — 15.071， P<0.001） were independent risk factors， and a nomogram was generated based on these factors. This model had an AUC of 0.836 in the training set， 0.881 in the internal validation set， and 0.878 in the external validation set， showing a good discriminatory ability. The calibration curve showed a good degree of fitting， with a relatively high net clinical benefit. The subgroup analysis based on etiology showed that the model had an AUC of 0.850 in the patients with HBV infection， 0.858 in the patients with alcohol-induced ACLF， and 0.908 in the patients with other etiologies， indicating that the model had a good discriminatory ability across the populations with different etiologies. Compared with traditional scores， the model （AUC=0.836） had a significantly better predictive value than MELD （AUC=0.619， Z=3.197， P=0.001）， MELD-Na （AUC=0.651， Z=2.998， P=0.003）， MELD 3.0 （AUC=0.601， Z=3.682， P<0.001）， and COSSH-ACLF Ⅱ （AUC=0.719， Z=2.396， P=0.017） alone. ConclusionDiabetes， SBP， and Cys-C are independent risk factors for 90-day mortality in patients with ACLF. Compared with MELD， MELD-Na， MELD 3.0， and COSSH-ACLF Ⅱ scores， this model has a higher predictive value for 90-day prognosis in patients with ACLF and is suitable for patients with ACLF caused by various etiologies.

Investigator initiated trial （IIT） represents a primary format for clinical research in traditional Chinese medicine （TCM）. As key implementation sites for TCM-based IIT targeting malignant tumors， western medicine institutions often face unique challenges in conducting such studies， which limit their feasibility and standardization. This paper reviews the registration status of TCM-based IIT for malignancies conducted in western medical institutions and analyzes key difficulties， including complex project initiation and management processes， limited TCM knowledge and skills among western medicine physicians， and relatively low patient acceptance of TCM. From a practical perspective， the study proposes several optimization strategies. These include improving the review and management mechanisms of TCM-related IIT within western medical institutions， establishing multidisciplinary clinical research teams that integrate TCM and western medicine， and enhancing investigators' training in TCM theory and clinical skills. Additionally， the study suggests standardizing IIT operational procedures， objectifying the collection of TCM diagnostic information， refining subject recruitment methods， and increasing TCM involvement in patient follow-up and management. These investigator-oriented， TCM-featured， and operable strategies aim to promote the high-quality development of TCM-based IIT in western medicine institutions and enhance the clinical application of TCM.

Chemotherapy based on cisplatin or its combination therapy is a common cancer treatment method. However， the non-specific side effects of cisplatin， poor pharmacokinetic properties of small molecule drugs， and susceptibility to drug resistance greatly limit the clinical application of cisplatin as first-line anti-tumor drug. With the development of nanocarrier technology， liposomes have become an ideal carrier for delivering cisplatin drugs due to their excellent properties of targeting， reducing toxicity， and enhancing efficacy. This paper reviews the status of cisplatin liposome both domestically and internationally which have entered clinical trials， including L-NDDP，SPI-077®， Lipoplatin®，LiPlaCis，SLIT and ILC， etc. Currently， only Lipoplatin® and ILC are showing good potential in cancer therapy. Although cisplatin liposome has made some progress in reducing systemic toxicity and improving treatment efficiency in clinical research， there is still potential for further improvement in tumor targeting and reducing side effects. In the future， more low-toxicity and efficient cisplatin liposomes can be developed through formulation technologies such as co-delivery liposome， stimuli-responsive liposome and targeting liposome.

ObjectiveTo investigate the preventive effect and mechanism of Dendrobium officinale （DO） on non-alcoholic fatty liver disease （NAFLD） by network pharmacology and animal experiments. MethodsDO components in blood after administration were identified and analyzed using ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-QE-HF-MS/MS）. Network pharmacology and molecular docking methods were employed to obtain active ingredients and potential targets of DO for NAFLD control. High-fat feeds were used to replicate the NAFLD rat model. Biochemical kits were used for detecting the expression levels of blood lipids， hepatic lipids， and liver functions of rats. Hematoxylin-eosin （HE） staining and oil red O staining were employed to observe pathological changes in rat liver， and real-time fluorescence quantitative PCR （Real-time PCR） assay was performed to validate potential targets obtained from the network pharmacology analysis. ResultsA total of 13 DO components were identified in blood， including berberine， dihydrosanguinarine， and oxypeucedanin. A total of 14 potential targets were screened through network pharmacology， including Forkhead box protein O1 （FoxO1）， epidermal growth factor receptor （EGFR）， and insulin-like growth factor 1 （IGF-1R）， involving pathways such as the advanced glycation end product （AGE）/receptor for AGE （RAGE） signaling pathway， blood lipids and atherosclerosis， insulin resistance， and FoxO signaling. The results of animal experiments showed that the NAFLD rat model was successfully replicated. After the preventive treatment with DO for NAFLD rats， the indexes of blood lipids， hepatic lipids， and liver function were normalized； lipid deposition and lesions in the liver were significantly improved； the expression level of FoxO1 mRNA in the liver was significantly reduced （P<0.05）， and the mRNA expression levels of phosphatidylinositide 3-kinases （PI3K）， protein kinase B （Akt）， EGFR， and IGF-1R were significantly increased （P<0.05）. ConclusionDO has a preventive effect on NAFLD rats， and the mechanism of action may be related to the modulation of IGF1R and EGFR targets and activation of the PI3K/Akt/FoxO1 signaling pathway.

This paper introduces the academic characteristics of Professor ZHANG Ren in treatment with acupuncture for refractory eye diseases in modern times, guided by "homotherapy for heteropathy" (same therapy for different diseases sharing the same pathogenesis). The refractory eye diseases in modern times include a variety of conditions such as glaucoma, macular degeneration, diabetic retinopathy, high myopia and its complications, dry eye, cortical visual impairment and genetic eye diseases. The same therapy is used because these diseases share the similar location and pathogenesis. Professor ZHANG optimizes the methods of acupoint selection and provides the comprehensive prescriptions, "basic prescription, prescription based on disease differentiation, and supplementary prescription". A variety of acupuncture manipulation techniques are operated in clinical practice, such as compound needling methods, penetration needling, manipulations for promoting qi movement and conducting qi flow. "Early, regular and persistent" treatment is the common requirement with "the same acupoints, the same prescription and the same acupuncture method" as well as at "the same time". It is also proposed that the treatment should be provided flexibly according to the different symptoms, "identifying the differences within similarities".
Acupuncture Therapy/methods* ; Humans ; Eye Diseases/history* ; Acupuncture Points ; History, 20th Century ; China ; History, 21st Century

OBJECTIVE: To analyze RELT gene mutation found in a pedigree with clinical features and inheritable pattern consistent with amelogenesis imperfecta (AI) in China, and to study the relationship between its genotype and phenotype. METHODS: Clinical and radiological features were recorded for the affected individuals. Peripheral venous blood samples of the patient and family members were collected for further study, and the genomic DNA was extracted to identify the pathogenic gene. Whole exome sequencing (WES) was performed to analyze the possible pathogenic genes, and Sanger sequencing was performed for validation. SIFT and PolyPhen-2 were used to predict and analyze the mutation effect. Comparison of RELT amino acids across different species were performed by using Uniprot website. In addition, the three-dimen-sional structures of the wild type and mutant proteins were predicted by Alphafold 2. RESULTS: The proband exhibited typical hypocalcified AI, with heavy wear, soft enamel, rough and discolored surface, and partial enamel loss, while his parents didn ' t have similar manifestations. WES and Sanger sequencing results indicated that the proband carries a homozygous frameshift mutation in RELT gene, NM_032871.3: c.1169_1170del, and both of his parents were carriers. This mutation was predicted to be pathogenic by SIFT and PolyPhen-2. Up to now, there were 11 mutation sites in RELT gene were reported to be associated with AI, and all of the patients exhibited with hypocalcified AI. Compared with the wild-type RELT protein, the mutant protein p. Pro390fs35 conformation terminated prematurely, affecting the normal function of the protein. CONCLUSION Through phenotype analysis, gene sequencing, and functional prediction of a Chinese family with typical amelogenesis imperfecta, this study found that RELT gene frameshift mutation can lead to protein dysfunction in AI patients. Further research will focus on the role and mechanism of RELT in enamel development at the molecular and animal levels, providing molecular biology evidence for the genetic counseling, prenatal diagnosis, and early prevention and treatment of AI.
Humans ; Amelogenesis Imperfecta/genetics* ; Frameshift Mutation ; Male ; Pedigree ; Female ; China ; Exome Sequencing ; Phenotype ; Adult

Objective To develop an endothelialized microfluidic chip model that simulates the spatial architecture and bioactivity of retinal vasculature,enabling thrombosis modeling and thrombolytic efficacy validation.Methods A tri-level microvascular network chip(300/200/100 μm diameters)with bifurcated architecture was fabricated using soft lithography.Human retinal microvascular endothelial cells(HRMECs)were perfused into channels,with endothelial coverage monitored via phase-contrast microscopy and F-actin staining.Cellular bioactivity was assessed using mitochondrial membrane potential probes(5,5,6,6-Tetrachloro-1,1,3,3-tetraethylbenzimidazolylcarbocyanine iodide,JC-1)and nitric oxide(NO)quantification.Fresh blood samples from 10 healthy donors(Yongchuan Hospital Affiliated to Chongqing Medical University,March to June 2024)were perfused with digital injection pump to mimic blood flow in human body into 3 experimental groups:normal whole blood,and TNF-α-activated endothelium+normal blood,TNF-α-activated endothelium+TNF-α-treated blood.Three inlet blood flow rates of 37.8、11.1 and 3.5 μL/min were set in each group.Two experimental groups,normal saline and recombinant human tissue-type plasminogen activator(rtPA),were established using the endothelialized microfluidic thrombosis model to validate thrombolytic efficacy.Endothelial functional impacts were assessed through integrated DAPI/NO staining and thrombosis model analysis across 3 intervention phases:pre-thrombosis,post-thrombosis,and post-thrombolysis.Results A tri-level microfluidic vascular model(300/200/100 μm diameters)was successfully constructed.In 72 h after endothelial cell perfusion,complete channel coverage was achieved,with phase-contrast microscopy and F-actin staining confirming confluent cellular alignment.JC-1/NO assays validated preserved endothelial bioactivity.Compared with the whole blood group,both TNF-α-activated endothelium+normal blood and TNF-α-activated endothelium+TNF-α-treated blood groups exhibited significantly increased thrombus occupancy rates at identical flow rates(all P<0.001).Notably,TNF-α-activated endothelium+TNF-α-treated blood group demonstrated the highest thrombus ratio at 3.5 μL/min(P<0.001).The rtPA group showed superior thrombolytic efficacy versus saline(P<0.001).Endothelial monolayer integrity was maintained across intervention phases,with thrombosis triggering significant NO elevation(P<0.001).Conclusion Our retinal vasculature-mimetic microfluidic model enables precise thrombosis modeling and drug evaluation,providing new methodology for studying retinal vascular occlusive diseases.

Objective:To analyze the current status of clinical research registration on TCM prevention and treatment of malignant tumors in the Chinese Clinical Trail Registry (ChiCTR); To summarize its characteristics and shortcomings.Methods:Clinical studies on the TCM prevention and treatment for malignant tumors registered from the establishment of ChiCTR database to July 15, 2024 were retrieved. Excel 2019 software was used to sort out the data, including basic research information (registration time, registration number status, registration title, test organizer, research implementation location, etc.), design scheme (disease type, research type, intervention measures, sample size, blind method, etc.), research funding or material sources, as well as other information such as human specimen collection and recruitment of research objects. SPSS 27.0 software was used for frequency statistics.Results:A total of 891 registered studies were included, including 783 interventional studies and 108 observational studies; the areas with a large number of registrations were mainly Shanghai, Beijing, Guangdong Province, etc. ; the research funds mainly came from local finance; a total of 46 tumor diseases were involved in the study, with the largest number of lung cancer (209 items), followed by tumor-related syndromes (155 items), colorectal cancer (148 items), and breast cancer (136 items); the type of research design was mainly random parallel control; the main intervention measures were TCM decoction or herbal decoction pieces (373 items), and the dosage form was mostly decoction (216 items), followed by granules (94 items); single-blind or double-blind design was used in 217 registered trials; 663 registration trials involved the collection of human samples.Conclusions:The number of clinical research registrations on the TCM prevention and treatment for malignant tumors is increasing day by day. The shortcomings such as insufficient standardization of research design and lack of research transparency still exists. In the future, TCM researchers need to strengthen cooperation with international traditional medicine clinical trial registry, giving full play to the leading role of standardization of TCM trials, and using registration as a starting point to improve the quality of clinical research.

ObjectiveTo investigate the efficacy of percutaneous transhepatic variceal embolization （PTVE） alone or in combination with partial splenic embolization （PSE） in the treatment of portal hypertensive hemorrhage in liver cirrhosis through a meta-analysis. MethodsThis study was conducted according to PRISMA guideline， with a PROSPERO registration number of CRD42023396690. Wanfang Med Online， CNKI， CBM， VIP Databases， PubMed， Embase， the Cochrane Library， and Web of Science databases were searched for articles on PTVE alone or in combination with PSE in the treatment of portal hypertensive hemorrhage in liver cirrhosis published up to December 23， 2022. The articles were selected based on inclusion and exclusion criteria， and related data were extracted. The RevMan 5.4.1 statistical analysis software was used to perform the meta-analysis. ResultsEight articles were finally included， with a total sample size of 592 cases， among which there were 316 cases in the PTVE+PSE group and 276 cases in the PTVE group. The meta-analysis showed that compared with the PTVE group， the PTVE+PSE group had significantly lower postoperative portal vein pressure （standardized mean difference ［SMD］=-1.75， 95% confidence interval ［CI］： -2.33 to -1.16， P<0.05）， postoperative diameter of the portal vein （SMD=-0.87， 95%CI： -1.64 to -0.10， P<0.05）， postoperative rebleeding rate （odds ratio ［OR］=0.17， 95%CI： 0.11 — 0.28， P<0.05）， mortality rate （OR=0.13， 95%CI： 0.04 — 0.37， P<0.05）， and incidence rate of postoperative portal hypertensive gastrointestinal disease （OR=0.17， 95%CI： 0.07 — 0.45， P<0.05］， as well as a significantly higher postoperative platelet level （SMD=0.79， 95%CI： 0.52 — 1.06， P<0.05）， while there were no significant differences between the two groups in the incidence rates of postoperative ascites. ConclusionCompared with PTVE alone， PTVE combined with PSE can effectively reduce the rebleeding rate and mortality rate of portal hypertensive hemorrhage in liver cirrhosis， the incidence rate of portal hypertensive gastrointestinal disease， and portal vein pressure， and it can also shorten the diameter of the portal vein and increase platelet level. Therefore， it is an effective interventional method for the treatment of portal hypertension hemorrhage in liver cirrhosis.

Objective: To investigate the epidemiological characteristics of varicella outbreaks in primary and middle schools, and to establish a risk predictive model, so as to provide scientific guidance for the prevention of varicella outbreaks in schools. Methods: Based on a nested case-control study, primary and middle schools in 4 districts of Shanghai (Yangpu District and Jingan District) and Hangzhou (Xiaoshan District and Linping District) from January to December 2023 were selected to observe the status of varicella outbreaks. Associated factors of varicella outbreaks were investigated and used for establishing the predictive model, which was evaluated by the Hosmer-Lemeshow(H-L) goodness of fit test, receiver operating characteristic (ROC) curve, Calibration curve, decision curve analysis (DCA). Results: A total of 98 varicella outbreaks were included, with 195 schools without varicella outbreaks during the same period as controls. Eight factors, including the availability of warm water in restroom, availability of hand soap in restroom, average class size, duration of student attendance at school per day, presence of a fulltime school doctor, hesitancy of the school principal towards varicella vaccination, and rates of first and second doses of varicella vaccination, were identified as potential factors for school varicella outbreaks, with statistically significant differences (χ2/Z=10.01, 20.49, 17.43, 9.74, 32.17, 6.60, 2.20, 3.39, P<0.05). The 8 variables above were employed to construct a risk predictive model, and Hosmer-Lemeshow goodness of fit test yielded a χ2 value of 5.863 (P>0.05); the area under the ROC curve (AUC) was 0.846 (95%CI=0.799-0.893); Calibration curve analysis indicated good consistency between predicted and actual values of the model. DCA demonstrated favorable predictive performance of the model over a wide range. Conclusions The predictive model for school varicella outbreaks demonstrates satisfactory accuracy and efficacy. It suggested to make good use of this prediction model and take relevant measures to reduce the risk of varicella transmission in schools.