ObjectiveTo explore the potential categories and characteristics of the public hospice care demand in Hainan Province， and analyze different potential types of influencing factors， so as to provide reference for relevant departments to improve the public awareness and demand of hospice care. MethodsUsing convenience sampling method， select 6484 cities of the public as the survey object， using the general data questionnaire， the hospice care demand questionnaire of the potential profile analysis， and analyze the influencing factors of the public hospice care demand category. ResultsThe characteristics of the hospice care demand in Hainan Province were divided into three potential categories： low demand group （14.19%）， medium demand group （49.99%） and high demand group （35.82%）. Multivariate analysis showed that gender， age， education level， cultural belief， and life-death education experience were the main influencing factors of public hospice care demand （p<0.05）. Males， those aged 41-60 years， and those with high school education or below had relatively lower hospice care demand， while those with life-death education experience had relatively higher demand. ConclusionRelevant departments should focus on hospice care knowledge popularization and demand enhancement for males， middle-aged groups， and people with low education levels， while strengthening universal life-death education through stratified and classified publicity strategies and educational interventions to improve different populations’ awareness and acceptance of hospice care.

ObjectiveBased on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance （IR） with type 2 diabetes mellitus （T2DM） were investigated. MethodsGoto-Kakizaki （GK） rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups： normal control group， model control group， metformin group （0.10 g·kg^-1）， and Huanglian Zhimutang group （3.60 g·kg^-1）， with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin （FINS） levels were measured using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. Total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin （HE） staining. Serum interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes （DEGs） in liver tissue from the normal control group， model control group， and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of insulin receptor substrate-1 （IRS-1）， PI3K， Akt， and peroxisome proliferator-activated receptor gamma （PPARγ） in liver tissue， while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention， typical symptoms of T2DM rats such as polydipsia， polyphagia， and polyuria were significantly alleviated， along with reductions in fasting blood glucose levels and insulin resistance（P<0.01）. Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC， TG， and LDL-C（P<0.01）. ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α（P<0.05，P<0.01）. Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue（P<0.05，P<0.01）， thereby reducing inflammation， alleviating hepatic lipid accumulation， and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway， which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.

ObjectiveBased on the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， the effects of Huanglian Zhimutang on glucose and lipid metabolism disorders and hepatic insulin resistance （IR） with type 2 diabetes mellitus （T2DM） were investigated. MethodsGoto-Kakizaki （GK） rats were fed a high-fat diet to induce a T2DM rat model and then randomly divided into four groups： normal control group， model control group， metformin group （0.10 g·kg^-1）， and Huanglian Zhimutang group （3.60 g·kg^-1）， with eight rats in each group. Drug intervention was administered continuously for 8 weeks. Serum and liver tissues were collected from each group. Fasting insulin （FINS） levels were measured using enzyme-linked immunosorbent assay （ELISA）， and the homeostasis model assessment of insulin resistance （HOMA-IR） index was calculated. Total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured using an automatic biochemical analyzer. Liver tissue pathology was observed via hematoxylin-eosin （HE） staining. Serum interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） levels were detected using ELISA. Network pharmacology and transcriptomics sequencing were combined to analyze differentially expressed genes （DEGs） in liver tissue from the normal control group， model control group， and Huanglian Zhimutang group. Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis was performed to identify pathways affected by Huanglian Zhimutang intervention in T2DM. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to assess the mRNA expression of insulin receptor substrate-1 （IRS-1）， PI3K， Akt， and peroxisome proliferator-activated receptor gamma （PPARγ） in liver tissue， while Western blot was used to evaluate corresponding protein expression levels. ResultsAfter 8 weeks of Huanglian Zhimutang intervention， typical symptoms of T2DM rats such as polydipsia， polyphagia， and polyuria were significantly alleviated， along with reductions in fasting blood glucose levels and insulin resistance（P<0.01）. Histopathological results revealed that Huanglian Zhimutang effectively improved hepatic steatosis and inflammatory edema and reduced lipid vacuole formation. Biochemical tests demonstrated that Huanglian Zhimutang significantly reduced serum levels of TC， TG， and LDL-C（P<0.01）. ELISA results showed that Huanglian Zhimutang effectively decreased serum concentrations of IL-6 and TNF-α（P<0.05，P<0.01）. Combined network pharmacology predictions with KEGG pathway analysis of transcriptomics showed that DEGs between the Huanglian Zhimutang and model control groups were significantly enriched in the PI3K/Akt signaling pathway. Real-time PCR and Western blot results confirmed that Huanglian Zhimutang upregulated the expression of PI3K/Akt signaling pathway-related mRNAs and proteins in liver tissue（P<0.05，P<0.01）， thereby reducing inflammation， alleviating hepatic lipid accumulation， and enhancing insulin sensitivity. ConclusionHuanglian Zhimutang effectively ameliorates glucose and lipid metabolism disorders in T2DM rats. Its mechanism may be related to the regulation of the PI3K/Akt pathway， which reduces inflammation and hepatic lipid deposition and relieves hepatic insulin resistance.

ObjectiveTo investigate the dynamic trajectories of prognostic scores and key clinical indicators in hepatitis B virus-related acute-on-chronic liver failure （HBV-ACLF） patients without liver cirrhosis， to clarify their association with outcomes， and to provide new evidence for individualized prognostic assessment. MethodsA prospective study was conducted for the data of 154 non-cirrhotic HBV-ACLF patients who attended Beijing YouAn Hospital of Capital Medical University from January 2016 to December 2023， including prognostic scores and key biochemical indicators on Days 3， 7， 14， 21， and 28 of the disease course. According to the outcome of patients at 1 year， they were divided into death/liver transplantation group with 43 patients， liver cirrhosis group with 23 patients， and non-liver cirrhosis group with 88 patients， and the trajectory heterogeneity of different outcome subgroups was analyzed. A one-way analysis of variance was used for comparison of normally distributed continuous data among the three groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data among the three groups； the Wilcoxon test was used between two groups. the chi-square test was used for comparison of categorical data between groups. The mean and its 95% confidence interval （CI） were calculated for each indicator at difference time points； the linear interpolation method was used to connect the means at adjacent time points and construct the group-specific longitudinal trend curve； the 95%CI was visualized using the semi-transparent ribbon area， with the transparency parameter （α=0.2） optimized to enhance the visual discrimination of overlapping intervals across multiple groups. A linear mixed-effects model was used to compare the longitudinal changing trend of each indicator between the patients with different outcomes； likelihood ratio was used to evaluate the significance of the interaction effect between time and group， and in case of the significant interaction effect， the slope based on the estimated marginal mean was used for comparison between two groups. ResultsThere were significant differences between the three groups in the incidence rates of ascites and grade Ⅲ — Ⅳ hepatic encephalopathy， MELD score， MELD-Na score， CLIF-C ACLF score， COSSH-ACLF Ⅱ score， total bilirubin （TBil）， international normalized ratio （INR）， alpha-fetoprotein， blood sodium， alanine aminotransferase， and procalcitonin at the baseline（all P0.05）. The analysis of dynamic trajectories showed that the death/liver transplantation group had high levels of prognostic scores and the biochemical parameters of TBil and INR （TBil400 μmol/L， INR2.5）， as well as a low level of platelet count （PLT） （100×10⁹/L）. The non-liver cirrhosis group had rapid improvements in indicators， with TBil200 μmol/L， INR1.5， and PLT100×10⁹/L by day 28， while the liver cirrhosis group showed a trend of recovery， with TBil200 μmol/L， INR2.0， and PLT 100×10⁹/L on day 28， with significant global heterogeneity in the temporal trends of the above indicators across the three groups （all P0.01）. ConclusionDynamic monitoring of prognostic scores and key clinical indicators can effectively stratify the 1-year outcomes of non-cirrhotic patients with HBV-ACLF. Patients with poor prognosis were typically characterized by INR 2.5 and TBil 400 μmol/L. Among those who survived beyond 1 year， individuals who subsequently progressed to cirrhosis were frequently identified by the presence of INR 1.5， TBil 200 μmol/L， and PLT 100×10⁹/L at day 28.

Objective:This study was aimed to evaluate the clinical effectiveness of tympanoplasty using auricular cartilage combined with balloon eustachian tuboplasty for the treatment of adhesive otitis media（adhesive otitis media, AdOM） under endoscopic. Methods:A retrospective analysis was conducted on 60 patients with unilateral adhesive otitis media who visited Department of Otolaryngology Head and Neck Surgery, the First Affiliated Hospital of Xiamen University between January 2017 and February 2022. All patients were divided into three groups: ①conservative treatment group;②simple tympanoplasty group; ③tympanoplasty combined with balloon dilation group（BET group）. All patients were regularly assessed for the improvement of tympanic membrane morphology, hearing, and Eustachian tube function, as well as complications, after treatment. Results:There was no significant improvement in eardrum morphology, hearing, or eustachian tube function in the conservative treatment group（P>0.05）; both the simple tympanoplasty group and the BET group showed significant improvements in eardrum morphology and hearing after surgery（P<0.01）; In terms of Eustachian tube function improvement, the BET group showed significantly greater improvements in Eustachian tube manometry（TMM） and Eustachian Tube Dysfunction Questionnaire（ETDQ-7） scores compared to the tympanoplasty alone group（P<0.01）. Conclusion:Tympanoplasty using auricular cartilage combined with balloon eustachian tuboplasty shows good clinical outcomes in the treatment of adhesive otitis media, significantly ameliorating patients' subjective symptoms such as tinnitus and ear congestion after surgery, thereby improving the patient's quality of life.
Humans ; Eustachian Tube/surgery* ; Retrospective Studies ; Tympanoplasty/methods* ; Otitis Media/surgery* ; Ear Cartilage/surgery* ; Endoscopy ; Dilatation ; Treatment Outcome ; Male ; Female ; Adult ; Middle Aged

Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective To explore the clinical effect and mechanism of Shenqi Shiyiwei granules(SQSYW)on improving colorectal cancer anemia.Methods Through database and network pharmacology analysis,the potential targets and core genes of SQSYW in the treatment of colorectal cancer anemia were obtained.The potential gene targets were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.A total of 80 patients with colorectal cancer anemia admitted in Sichuan Provincial Hospital of Integrated Traditional Chinese and Western Medicine were selected as subjects,according to the treatment plan,they were divided into experimental group(n=40)and control group(n=40).Control group received standard Western medical treatment including subcutaneous erythropoietin injections,while experimental group received additional administration of SQSYW on the base of control group's treatment regimen.Effective treatment rates,TCM symptom score,hemoglobin levels,and red blood cell counts were compared between two groups.Results Five key active ingredients,10 core targets and 30 main pathways were identified through pharmacological screening.Red blood cell count,hemoglobin,TCM syndrome and overall western medicine efficacy were better in experimental group than in control group(P＜0.05).Conclusion SQSYW can treat colorectal cancer anemia through multiple components,multiple targets and multiple pathways.The treatment effect of colorectal cancer anemia combined with SQSYW is better than that of simple western medicine.

Objective To explore the clinical effect and mechanism of Shenqi Shiyiwei granules(SQSYW)on improving colorectal cancer anemia.Methods Through database and network pharmacology analysis,the potential targets and core genes of SQSYW in the treatment of colorectal cancer anemia were obtained.The potential gene targets were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.A total of 80 patients with colorectal cancer anemia admitted in Sichuan Provincial Hospital of Integrated Traditional Chinese and Western Medicine were selected as subjects,according to the treatment plan,they were divided into experimental group(n=40)and control group(n=40).Control group received standard Western medical treatment including subcutaneous erythropoietin injections,while experimental group received additional administration of SQSYW on the base of control group's treatment regimen.Effective treatment rates,TCM symptom score,hemoglobin levels,and red blood cell counts were compared between two groups.Results Five key active ingredients,10 core targets and 30 main pathways were identified through pharmacological screening.Red blood cell count,hemoglobin,TCM syndrome and overall western medicine efficacy were better in experimental group than in control group(P＜0.05).Conclusion SQSYW can treat colorectal cancer anemia through multiple components,multiple targets and multiple pathways.The treatment effect of colorectal cancer anemia combined with SQSYW is better than that of simple western medicine.

Objective:To explore the application effect of Kaitianmen point massage on pain, faligue, anxiety and depression in patients with rheumatoid arthritis.Methods:This study was a randomized controlled study, a total of 80 patients with rheumatoid arthritis who were admitted to Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine from May to November 2023 were selected as the research objects. The control group was given routine treatment and nursing, and the experimental group was given Kaitianmen acupoint massage on the basis of routine treatment and nursing. The differences in pain score, fatigue score, anxiety and depression score before and after intervention were compared between the two groups.Results:In the final, there were 37 cases in the experimental group and 36 cases in the control group completed the study. Before intervention, there was no statistically significant difference in pain scores, fatigue scores, anxiety and depression scores between the two groups (all P>0.05). After four weeks of intervention, the pain score of the experimental group was (2.06 ± 0.35), and that of the control group was (3.72 ± 0.59), the difference was statistically significant ( t=14.57, P<0.05). After four weeks of intervention, the fatigue score of the experimental group was (20.11 ± 8.03), and that of the control group was (25.02 ± 8.32), the difference was statistically significant ( t=2.55, P<0.05). After four weeks of intervention, the anxiety score of the experimental group was (48.33 ± 6.13), which was significantly different from (53.99 ± 4.91) of the control group ( t=4.35, P<0.05), and the depression score of the experimental group was (49.99 ± 6.33), compared with the (54.86 ± 4.83) of control group, the difference was statistically significant ( t=3.69, P<0.05). Conclusions:Kaitianmen acupoint massage can relieve limb pain, fatigue, anxiety and depression in patients with rheumatoid arthritis, which is worthy of clinical promotion.

Objective To establish the content determination method of Zhihuoding granules(ZHDG)by the anti-inflammatory active ingredients and fingerprint.Methods The inflammatory model of BEAS-2B cells was established by LPS(10 μg·mL-1)stimulation for 24 h,and the level of TNF-α in the supernatant was detected by enzyme-linked immunosorbent assay(ELISA).Using the reverse high-performance liquid chromatography(RP-HPLC)of 7 batch ZHDG fingerprint;HPLC was used to determine the content of geniposide and baicalin in granules.Results Compared with LPS Group,ZHDG,prim-O-glucosylcimifugin,5-O-methylvisammioside,baicalin,geniposide,and total polysaccharide extract all significantly decreased TNF-αlevels in BEAS-2B cells induced by LPS(P＜0.05).Fingerprint spectra of 7 batches of ZHDG were established,with a similarity of 1.000 to the reference.A total of 15 peaks were calibrated,and 7 chromatographic peaks were identified.Gardenin and baicalin were selected as the index components of ZHDG for evaluation.The established method was rapid and accurate.Conclusion The method for the determination of baicalin and geniposide in ZHDG are exclusive,accurate,and effective,providing reference for the quality control and clinical application of ZHDG.