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.

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.

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.

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 evaluate the impact of cold-air anesthesia on patients′ comfort and side effects during ablative fractional carbon-dioxide (CO 2) laser treatment for acnescars. Methods:Eighteen patients with atrophic acne scars treated with CO 2 laser were used as split-face comparative study with a cold-air device combined with 5% lidocaine cream on the left side of the face, and the right side as a control group treated with 5% lidocaine cream only. Symptoms and signs of patients were observed during treatment, immediately after treatment, 15 minutes, 30 minutes and 1 month after treatment. The score of patient′s comfort and incidence of adverse events was evaluated. Results:The results were obvious difference between each group. The surface temperature in combined group (33.1±1.3) showed significantly better results compared with other groups (36.9±0.4) during the operative period while the same result after the treatment immediately shown in the combined group (35.1±1.3) compared with other groups (36.4±0.2). The score of erythema shown that combined group (48.7±8.4) was significantly lower than that of the control group (54.8±8.0) ( P<0.05) as the score of exudation in combined group (6.2±1.6) was lower than that in the control group (7.8±1.6). There was significant statistical difference regarding scores of erythema between combined group (46.9±6.6) and control group (51.8±6.9) a month after the treatment. The pigmentation score revealed the same result that the combined group (48.9±8.8) was lower than the other groups (51.4±7.0). No patients had severe adverse events. Conclusions:The cold-air cooling application is safe and effective to reduce the surface temperature, pain and side effects during fractional carbon-dioxide laser treatment.

Objective To explore the application effect of upper abdominal moxibustion combined with bedside ultrasound monitoring of gastric residual volume(GRV)in pre-pyloric feeding in stroke patients.Methods Eighty stroke patients admitted to the Department of Rehabilitation Medicine of Zhejiang Provincial People's Hospital from January 1,to December 31,2023 were selected as the study subjects.They were divided into control group(n=38)and observation group(n=42)using a random number table method.All patients had a nasogastric tube for pre-pyloric feeding.The control group used the traditional syringe aspiration method to monitor GRV,while the observation group used upper abdominal moxibustion combined with bedside ultrasound to monitor GRV.The study compared the differences between two groups in terms of enteral nutrition intolerance,feeding complications,enteral nutrition compliance rate within 7 days of admission,time to achieve enteral nutrition compliance,and changes in hemoglobin(Hb),serum prealbumin,serum albumin(ALB),and serum transferrin before and after 14 days of feeding.Results The incidence rates of vomiting,abdominal distention,intra-abdominal hypertension,reflux,and aspiration pneumonia in observation group were lower than those in control group(P＜0.05).The rate of achieving intestinal nutrition standard within 7 days of hospitalization was significantly higher in observation group compared to the control group.The time to achieve intestinal nutrition standard was shorter in observation group compared to control group.Furthermore,after 14 days of feeding,the levels of Hb and ALB in observation group were higher than those in control group,and the differences were statistically significant(P＜0.05).Conclusion Upper abdominal moxibustion combined with bedside ultrasonic monitoring of GRV can significantly reduce intestinal nutrition intolerance and feeding complications during pre-pyloric feeding in stroke patients,shorten the time to achieve nutritional benchmarks,and improve nutritional status.

As a noval class of nucleic acid drugs,messenger ribonucleic acid(mRNA)has great application potential in vaccines,immunotherapy,regenerative medicine,gene editing and so on.In particular,coronavirus disease 2019(COVID-19)in 2020 has greatly accelerated the mRNA technology development globally.However,mRNA being negatively charged,face challenges in cell entry and is easy to be phagocytized by cells of the innate immune system or degraded by nucleases in vivo.The instability and low delivery efficiency hinder widespread application of mRNA-based therapy.Therefore,safe,effective and stable delivery was needed carriers to protect mRNA from degradation and break through the barrier of cell membrane in order to ensure it express in intracellular.This paper systematically reviews the latest research progress of mRNA delivery carriers and briefly describes lipid carriers,polymer carriers,peptide carriers and viral carriers.The future directions of mRNA delivery carriers research are prospected so as to provide reference for the development of new mRNA drug delivery carriers.

AIM:To explore the effect of polyphenolic compound 3,5-dihydroxy-4-methoxybenzyl alcohol(DHMBA)on hypoxia/reoxygenation(H/R)injury of human umbilical vein endothelial cells(EA.hy926 cells)and its po-tential mechanisms.METHODS:To construct an H/R model,the EA.hy926 cells were cultured in an acidic hypoxia buffer while in an anaerobic workstation.The cells were divided into control,H/R,H/R+different doses of DHMBA,H/R+edaravone(antioxidant)and H/R+reactive oxygen species(ROS)inducer oligomycin A+DHMBA groups.Cell viability was measured by CCK-8 assay,and tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)levels in cells were mea-sured by ELISA.Phosphorylation of endothelial nitric oxide synthase(eNOS)and nuclear factor-κB(NF-κB)p65 were measured by Western blot.Intracellular NO levels were determined by laser confocal microscopy.Glutathione(GSH)/glu-tathione disulfide(GSSG)oxidation balance was determined by the dinitrobenzoic acid chromogenic method.Intracellular ROS levels were measured by flow cytometry.Lactate dehydrogenase(LDH)leakage was determined using nitro blue tet-razolium staining.Scratch assays were performed to assess cell migration.RESULTS:DHMBA exhibited no significant cytotoxicity between 125 and 1 000 μmol/L.In H/R-injured human umbilical vein endothelial cells,DHMBA improved cell survival,inhibited phosphorylation of NF-κB p65,reduced the content of TNF-α and IL-6,and increased phosphory-lation of eNOS and NO levels.DHMBA also suppressed ROS overload and restored the ratio between GSH and oxidized GSH,decreased in LDH leakage and increased cell migration in H/R-injured human umbilical vein endothelial cells.CONCLUSION:DHMBA can alleviate H/R-induced oxidative stress,inflammation,cellular damage,and dysfunction,which are associated with the ability of DHMBA to inhibit ROS production in human umbilical vein endothelial cells.