Patients with alcoholic cirrhosis often experience varying degrees of malnutrition， and the patients with malnutrition are more susceptible to complications such as infections and ascites， which may lead to a poor prognosis. Therefore， it is particularly important to conduct nutritional risk screening for patients in clinical practice， and appropriate nutritional assessment tools should be used to evaluate the nutritional status of patients and develop individualized nutritional supplementation regimens， thereby promoting disease recovery and improving prognosis and quality of life. This article elaborates on the specific methods for nutritional screening， assessment， and management in patients with alcoholic cirrhosis and points out that systematic nutritional screening and assessment can help to identify the patients with malnutrition in the early stage and provide timely intervention. Individualized nutritional supplementation regimens should be adjusted based on the conditions of patients， so as to meet their nutritional needs， promote the recovery of liver function， improve overall health status， and enhance long-term quality of life.

Objective:To observe the effect of bone forming protein 4 (BMP4) on the proliferation and migration of human retinal pigment epithelium (RPE) cells under oxidative stress, and to preliminarily explore its effect on epithelial-mesenchymal transition (EMT) of RPE cells.Methods:Human RPE cells cultured in vitro were divided into normal group, pure 4-hydroxynonenal (HNE) group (4-HNE group), 4-HNE+NC group and 4-HNE+ small interfering BMP (siBMP4) group. The effect of 4-HNE on the proliferation of RPE cells was detected by thiazole blue colorimetry. The effects of 4-HNE and BMP4 on cell migration were determined by cell scratch test. The expression of BMP4 was detected by immunofluorescence staining, Western blot and real-time quantitative polymerase chain reaction. The transfection efficiency of siBMP4 was observed by fluorescence microscopy. Mitochondrial reactive oxygen species (MitoSOX) were detected by flow cytometry. The expression of EMT markers E-cadherin and Fibronection were detected by immunofluorescence assay. t-test was used for comparison between the two groups, and one-way analysis of variance was used for comparison between the three groups. Results:Compared with normal group, cell proliferation and migration ability of 4-HNE group were significantly enhanced, with statistical significance ( t=21.619, 24.469; P<0.05). The expression of BMP4 in cells was significantly increased, and the difference was statistically significant ( t=19.441, P<0.05). The relative expression levels of BMP4 mRNA and protein were also significantly increased, with statistical significance ( t=26.163, 37.163; P<0.05). After transfection with siBMP4 for 24 h, the transfection efficiency of BMP4 in RPE cells was>90%. Compared with 4-HNE group and 4-HNE+NC group, the relative expression levels of BMP4 protein ( F=27.241), mRNA ( F=36.943), cell mobility ( F=46.723) and MitoSOX expression levels ( F=39.721) in normal group and 4-HNE+siBMP4 group were significantly decreased. The differences were statistically significant ( P<0.05). The epithelial marker E-cadherin increased significantly, while the mesenchymal marker Fibronection decreased significantly, with statistical significance ( F= 51.722, 45.153; P<0.05). Conclusions:BMP4 inhibits RPE proliferation and migration under oxidative stress. BMP4 is involved in inducing EMT in RPE cells.

Objective:To explore the effect of cathepsin L (CTSL) inhibitor on apoptosis of retinal pigment epithelial (RPE) cells and mitochondrial oxidative stress.Methods:RPE cells were cultured in vitro and divided into control group, hydrogen peroxide (H 2O 2) group, and H 2O 2+CTSL inhibitor group. The cells of H 2O 2 group and H 2O 2+CTSL inhibitor group were incubated in the medium containing 400 μmol/L H 2O 2 for 24 hours and 10 μmol/L CTSL inhibitor was added in H 2O 2+CTSL inhibitor group at the same time. The cells of normal group were routinely cultured cells. The follow-up experiment was carried out 24 hours after modeling. The rate of apoptosis was detected by flow cytometry. The expression of CTSL was detected by immunofluorescence staining, Western blot and real time-polymerase chain reaction. The level of mitochondrial super oxide was detected by MitoSOX fluorescent probe, and the mitochondrial structure was observed after MitoTracker staining, the average area, form factors, and branch of mitochondria were quantitatively analyzed. The two groups were compared using two-tailed Student t test, while numerous groups were compared using one-way ANOVA. Results:Compared with control group, the rate of apoptosis in H 2O 2 group was significantly higher ( t=3.307, P=0.029 7), the expression level of CTSL was significantly increased ( t=19.950, 6.916, 14.220; P<0.05). Compared with H 2O 2 group, the expression level of CTSL, the rate of apoptosis and the mitochondrial ROS level in H 2O 2+CTSL inhibitor group were significantly lower ( t=11.940, 4.718, 16.680; P<0.05). The mitochondria of H 2O 2+CTSL inhibitor group were elongated, oval-shaped or rod-shaped, while the mitochondria of H 2O 2 group lost their continuous contour shape and complete structure. The differences of the average area, form factors, and brach of mitochondria among 4 groups were statistically significant ( F=251.700, 34.010, 60.500; P<0.000 1). Conclusions:H 2O 2 can significantly induce apoptosis in RPE cells and increase CTSL expression. CTSL inhibitor can inhibit the H 2O 2-induced apoptosis of RPE cells, lower the mitochondrial super oxide level, and successfully repair the mitochondrial structure.

Objective:To observe the effects of NDRG1 on proliferation, migration and lumen formation of retinal vascular endothelial cells (RF/6A cells) in monkeys under high glucose condition. Methods:RF/6A cells were divided into normal group, mannitol group, high glucose group, small interfering RNA (siRNA) negative control group without target gene (siRNA group), 30 nmol/L siRNA down-regulated NDRG1 genome (siNDRG1 group) and 50 nmol/L siNDRG1 group. Normal group cells were cultured conventionally. The mannitol group was added with 25 mmol/L mannitol, and the high-glucose group was added with 25 mmol/L glucose. In the siRNA group, 25 mmol/L glucose was added, and then blank siRNA was added for induction. The 30 and 50 nmol/L siNDRG1 groups were added with 25 mmol/L glucose and induced with 30 and 50 nmol/L siRNDRG1, respectively. All cells were incubated for 24 h for follow-up experiments. Cell proliferation was observed by 4', 6-diaminidine 2-phenylindole staining. Cell counting kit-8 staining was used to detect cell activity. The expression level of NDRG1 mRNA and protein was detected by Western blot and real-time quantitative polymerase chain reaction. Cell migration was observed by cell scratch assay. Cell lumen formation assay was used to detect lumen formation. The two-tailed Student t test was used to compare the two groups. One-way analysis of variance was used to compare groups. Results:There were significant differences in cell proliferation rate ( t=36.659, 57.645) mobility rate ( t=24.745, 33.638) and lumen formation number ( t=41.276, 22.867) between high glucose group and normal group and mannitol group ( P <0.01). Compared with normal group and mannitol group, the relative expression levels of NDRG1 gene mRNA and protein in high glucose group were significantly decreased, with statistical significance ( t=46.145, 21.541, 36.738, 32.976; P<0.001). Compared with the siRNA negative group, the relative expression levels of NDRG1 gene mRNA and protein in 30 nmol/L siNDRG1 group and 50 nmol/L siNDRG1 group were significantly decreased, and the differences were statistically significant ( t=44.275, 40.7577, 57.167, 25.877; P<0.01). Compared with normal group and siRNA group, cell mobility in 30 nmol/LsiNDRG1 group was increased, and the difference was statistically significant ( t=57.562, 49.522; P<0.01). Compared with normal group and siRNA group, the number of cell lumen formation in 30 nmol/LsiNDRG1 group was significantly increased in the same field of vision, and the difference was statistically significant ( t=63.446, 42.742; P<0.01). Conclusion:Down-regulation of NDRG1 gene can improve the activity, migration and lumen formation of RF/6A cells under hyperglycemia.

Objective:To observe the effect of Nodal on the biological behavior of retinal vascular endothelial cells (RF/6A cells) in monkeys with high glucose.Methods:RF/6A cells were divided into normal group, mannitol group, high glucose group, high glucose combined with non-specific small interfering RNA treatment group (HG+NC group), high glucose combined with small interfering Nodal treatment group (HG+siNodal group). The transfection efficiency of siNodal was observed by real-time fluorescence quantitative PCR and western blot protein immunoblotting. The effect of Nodal on the proliferation of RF/6A cells was detected by thiazole blue colorimetry. The effect of Nodal on migration ability of RF/6A cells was detected by cell scratch assay. The effect of Nodal on the formation of RF/6A cell lumen was measured by Matrigel three-dimensional in vitro. The expression of extracellular signal phosphorylated regulated kinase 1/2 (pERK1/2) in RF/6A cells was detected by western blot protein immunoblotting. One-way analysis of variance was used to compare groups.Results:Compared with HG+NC group, Nodal protein ( F=33.469) and mRNA relative expression levels ( F=38.191) in HG+siNodal group were significantly decreased, cell proliferation was significantly decreased ( F=28.548), and cell migration ability was significantly decreased ( F=24.182). The number of cell lumen formation was significantly decreased ( F=52.643), and the differences were statistically significant ( P<0.05). Compared with HG+NC group, the relative expression of pERK1/2 protein in HG+siNodal group was significantly decreased, and the difference was statistically significant ( F=44.462, P<0.01). Conclusions:Silencing Nodal expression can inhibit proliferation, migration and tube formation of RF/6A cells induced by high glucose. It may act by inhibiting pERK1/2 expression.

Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.

Drug loading is an important index to evaluate the quality of solid preparation of traditional Chinese medicine. Drug loading is restricted by drug characteristics, dosage form, process, and drug delivery in vivo, which affects the preparation process, therapeutic effect, and drug release rate. By consulting domestic and foreign literature, this paper put forward the significance of increasing the drug loading: improving the compliance of patients, reducing the production cost, reducing the risk of the excipients. In this review, the possible approaches to increase drug loading, such as the selection of high-efficiency excipients, suitable drug preparation techniques, and modification of the physical properties of drugs are summarized. It will provide theoretical basis through this review for the development of high drug loading and high-quality formulations.

Objective This study investigated the epidemic characteristics and spatio-temporal dynamics of hemorrhagic fever with renal syndrome (HFRS) in Qingdao City,China. Methods Information was collected on HFRS cases in Qingdao City from 2010 to 2022. Descriptive epidemiologic,seasonal decomposition,spatial autocorrelation,and spatio-temporal cluster analyses were performed. Results A total of 2,220 patients with HFRS were reported over the study period,with an average annual incidence of 1.89/100,000 and a case fatality rate of 2.52％. The male:female ratio was 2.8:1. 75.3％ of patients were aged between 16 and 60 years old,75.3％ of patients were farmers,and 11.6％ had both "three red" and "three pain" symptoms. The HFRS epidemic showed two-peak seasonality:the primary fall-winter peak and the minor spring peak. The HFRS epidemic presented highly spatially heterogeneous,street/township-level hot spots that were mostly distributed in Huangdao,Pingdu,and Jiaozhou. The spatio-temporal cluster analysis revealed three cluster areas in Qingdao City that were located in the south of Huangdao District during the fall-winter peak. Conclusion The distribution of HFRS in Qingdao exhibited periodic,seasonal,and regional characteristics,with high spatial clustering heterogeneity. The typical symptoms of "three red" and"three pain" in patients with HFRS were not obvious.

Objective To observe the change of human urinary microalbumin(MA)and α1-microglobulin(α1-MG)after different intensities and duration of+Gz exposure,and explore the effect of+Gz exposure on renal function.Methods Urinary samples of 62 young health male subjects were collected after human centrifuge training,the highest+Gz exposure intensity and duration were+6.5 G/10 s for group A(n=15),+6.5 G/45 s for group B(n=11),+8 G/10 s for group C(n=23)and+9 G/10 s for group D(n=13)respectively.Urinary MA and α1-MG were measured before and 2 hours and 24 hours after centrifuge training by rate scatteringimmune turbidimetric.The results were compared between four groups and between the different time after centrifuge training.Results The levels of urinary MA and α1-MG significantly increased 2 hours after training(P<0.05,P<0.01),and urinary MA of groups B,D were significantly higher than those of groups A,C(P<0.05,P<0.01).In subjects of A,B,C and D groups,the ratio of urinary MA beyond the normal value were 13.3%、54.5%、17.4%and 53.8%respectively and the ratio of urinary α1-MG beyond the normal value were 26.7%、36.4%、26.1%and 38.5%respectively.Urinary MA and α1-MG of four groups decreased 24 hours after centrifuge training,there were no significant changes compared with those before training(P>0.05),and all returned to normal levels within 48 hours after training.Conclusion Moderate and high level of+Gz exposure may cause recoverable glomeruli and renal tubule function abnormalities.This effect aggravates with the increase of+Gz exposure intensity,duration and has individual differences.The study shows that human renal function should be tested and careful protected after high intensity+Gz exposure.