Objective To explore the mediating role of activities of daily living (ADL) in pain and depressive symptoms in the elderly in China. Methods Utilizing the data from 2020 China Health and Retirement Longitudinal Study, 4403 Chinese elderly individuals aged ≥ 60 years old were selected as the research subjects. Depression Scale (CES-D 10) of the Center for Epidemiological Survey and ADL scale were used in the study. The PROCESS4.1 macro was used to test the mediating effect of daily living activities between pain and depressive symptoms, and the Bootstrap method was applied for verification of the mediating variables. Results A total of 2368 cases of depressive symptoms were detected in the elderly in China, with a detection rate of 53.78%. Pain was positively correlated with depressive symptoms (r=0.27, P<0.01), and activities of daily living were negatively correlated with pain and depressive symptoms (r=-0.27, -0.337, P<0.01). The results showed that the total effect value of pain on depressive symptoms was 0.33, the direct effect value was 0.24, and the mediating effect value of daily living activities was 0.09, accounting for 27.27%. Conclusion Pain and activities of daily living are important factors influencing depressive symptoms in the elderly, and activities of daily living play a partial mediating role in the relationship between pain and depressive symptoms in the elderly.

ObjectiveTo investigate the influence of empagliflozin combined with donafenib or lenvatinib on the pharmacokinetic parameters of each drug， and to provide a reference for combined medication in clinical practice. MethodsA total of 48 healthy male Sprague-Dawley rats were divided into 8 groups： empagliflozin group 1 and 2， donafenib group， lenvatinib group， donafenib pretreatment+empagliflozin group， lenvatinib pretreatment + empagliflozin group， empagliflozin pretreatment+donafenib group， and empagliflozin pretreatment+lenvatinib group， with 6 rats in each group. The doses of empagliflozin， donafenib， and lenvatinib were 2.5 mg/kg， 40 mg/kg， and 1.2 mg/kg， respectively. The rats in the empagliflozin group， donafenib group， and lenvatinib group were given a blank solvent by gavage for 7 consecutive days， followed by a single dose of empagliflozin， donafenib， or lenvatinib on day 7 after the administration of the blank solvent； the rats in the pretreatment groups were given the pretreatment drug by gavage for 7 consecutive days， followed by a single dose of drug combination on day 7 after administration of the pretreatment drug. Blood samples were collected at different time points， and plasma was separated to measure the concentration of each drug. A validated ultra-performance liquid chromatography-tandem mass spectrometry method was used to measure the plasma concentrations of donafenib， lenvatinib， and empagliflozin， and a non-compartmental model was used to calculate the main pharmacokinetic parameters of each drug （area under the plasma concentration-time curve ［AUC］， time to peak ［T_max］， peak concentration ［C_max］， and half-life time ［t_1/2］）. 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. ResultsCompared with the empagliflozin group， the donafenib pretreatment+empagliflozin group had significant increases in the AUC_0-t and AUC_0-∞ of empagliflozin （P=0.011 and 0.008）， while the lenvatinib pretreatment+empagliflozin group had no significant change in the AUC of empagliflozin， with a slightly shorter T_max （P=0.019）. Compared with the donafenib group， the empagliflozin pretreatment+donafenib group had significant increases in the AUC_0-t and AUC_0-∞ of donafenib （P=0.027 and 0.025）， as well as a significant increase in C_max （P=0.015） and significant reductions in CLz/F and Vz/F （P=0.005 and 0.004）； compared with the lenvatinib group， the empagliflozin pretreatment+lenvatinib group had a reduction in the t_1/2 of lenvatinib by approximately 5 hours （P=0.002）， with a trend of reduction in AUC_0-t （P0.05）. ConclusionEmpagliflozin combined with donafenib may alter the pharmacokinetic parameters of both drugs， leading to a significant increase in the exposure levels of both drugs， and efficacy and adverse reactions should be monitored during co-administration. There are no significant changes in the exposure levels of empagliflozin and lenvatinib during co-administration.

There is a certain correlation and interaction between circulating tumor cells and recurrence-metastasis of colorectal cancer. The circulating tumor cells hidden in the human body can lead to the recurrence and metastasis of colorectal cancer， and the recurrence and metastasis of colorectal cancer can in turn cause a sharp increase in the number of circulating tumor cells， which is consistent with the characteristics of latent pathogens in traditional Chinese medicine leading to diseases. Starting from the theory of latent pathogens， this article summarized the etiology and disease mechanism of recurrence-metastasis of colorectal cancer as harmed healthy qi， latent pathogenic qi， prolonged latent pathogens， and triggering healthy qi deficiency. This article also proposes four major treatment methods as reinforcing healthy qi， assisting yang， opening the exterior， and expelling pathogen， in order to provide ideas and methods for the prevention and treatment of recurrence and metastasis of colorectal cancer.

Peripapillary pachychoroid syndrome (PPS), a new entity in pachychoroid disease spectrum, is characterized by the thickening of the choroid in the peripapillary area.PPS is more likely to occur in middle-aged and older males, and some of the affected eyes are hyperopic and have short axial lengths.The diagnosis and differentiation of PPS depends mainly on the imaging characteristics.Optical coherence tomography shows that dilated Haller layer vessels are located in the nasal macula and associated with intraretinal fluid in the corresponding locations.Indocyanine green angiography shows dilated large choroidal vessels and choroidal hyperpermeability in the nasal maculal and peripapillary region.PPS should be differentiated from uveal effusion syndrome, central serous chorioretinopathy, and pachychoroid neovascularization.Photodynamic therapy may improve retinal effusion in patients with PPS.At present, the research on PPS is insufficient.It is still controversial whether PPS can be considered as a separate entity.The effectiveness of treatment needs more prospective studies.Further research is needed to provide new insights into the definition, diagnosis, treatment and pathogenesis of PPS.

Objective:To explore the neuroprotective effects and mechanisms of memantine on sepsis-associated encephalopathy (SAE) model mice.Methods:Totally 90 male C57BL/6J mice aged 8-12 weeks were randomly divided into 3 groups (with 30 mice in each group) : sham group, model group and memantine group. The SAE mouse model was established by cecum ligation and puncture while mouse in sham group received open and closed abdomen only. The mice in the memantine group were irrigation with memantine (15 mg · kg -1· d -1) 3 hours before surgery and 7 consecutive days after modeling. The mice in the model group and sham group were irrigation with an equal volume of 0.9% sodium chloride solution. The 7-day survival rate was observed, neurobehavioral and cognitive function scores of each group of mice after modeling were assessed.Blood-brain barrier permeability was measured by detecting the content of Evans blue. Immunofluorescence staining was used to detect the expression of astrocytes. Enzyme linked immunosorbent assay was conducted to detect cellular inflammatory factors and the glutamic acid content detection kit was used to detect the expression of glutamic acid. All data were analyzed by Graphpad Prism 8.3.0 software, survival rate was analyzed using Kaplan-Meier survival curve.Multigroup comparisons were conducted by one-way ANOVA or Kruskal-Wallis test. Results:(1) There was a statistically significant difference in the 7-day survival rate among the three groups of mice after modeling ( F=24.11, P<0.01), and the 7-day survival rate of the memantine group was higher than that of the model group (57% (17/30), 27% (8/30), P<0.01). (2)The behavioral results showed that after 7 days of modeling, there were statistically significant differences in the total distance of the open field test, central area stay time, four corner area stay time, neurobehavioral scores, pole climbing test, and preference index for new object recognition test among the three groups of mice ( F/ χ2=17.67, 17.30, 9.39, 14.06, 10.36, 14.81, all P<0.05).The neurobehavioral score, pole climbing test score, preference index for new object recognition test, total distance of open field test, and central area stay time of the model group were all lower than those of the sham group (all P<0.05), while four corner area stay time of the model group was higher than that of the sham group ( P<0.05).The total distance of open field test (1 564.07(1 363.24, 1 988.19) cm, 913.91 (574.32, 1 096.23) cm), central area stay time (5.21 (4.91, 8.76) s, 1.09 (0.25, 1.64) s), neurobehavioral scores (9.75±0.50, 8.25±0.50), pole climbing test scores (5.67±0.52, 4.56±0.53), and preference index for new object recognition test (56.50±10.59, 26.84±2.91) of the memantine group were all higher than those of the model group (all P<0.05). The four corner area stay time was lower than that of the model group ((480.30±50.64) s, (529.80±36.20) s, P<0.05).(3)The comparison of molecular indicators showed that there were statistically significant differences in the content of Evans blue in the brain, the number of astrocytes in the hippocampus and cerebral cortex, pro-inflammatory cytokines (TNF-α、IL-1β、IL-6), anti-inflammatory cytokines (IL-10), and glutamic acid among the three groups of mice ( F/ χ2=8.84, 6.43, 28.46, 23.63, 12.23, 16.04, 69.22, 6.65, all P<0.05).The content of Evans blue, the number of astrocytes in the hippocampus and cerebral cortex, the expression of TNF-α、IL-1β、IL-6, and glutamate in the model group were all lower than those in the sham group(all P<0.05). The levels of IL-10 in the model group was lower than that in the sham group ( P<0.05).The content of Evans blue ((5.67±1.38)μg/g, (11.08±2.79)μg/g), the number of astrocytes in the hippocampus (16.50 (13.75, 22.25)/μm 2), 80.00 (73.50, 83.50)/μm 2) and the cerebral cortex (40.00 (29.00, 48.00)/μm 2, 81.50 (72.25, 89.00)/μm 2) in the memantine group were lower than those in the model group (all P<0.05).The pro-inflammatory factor TNF-α, IL-1β, IL-6 and glutamic acid expression in the memantine group were lower than those in the model group (all P<0.05), and the anti-inflammatory cytokine IL-10 was higher than that in the model group ( P<0.05). Conclusions:Memantine can improve the neurobehaviors and cognitive functions of SAE mice through improving the integrity of the damaged blood-brain barrier, alleviating inflammation in the brain, as well as reducing glutamate levels in the brain.

Objective To investigate the role of sodium-glucose cotransporter 1(SGLT1)inhibitor mizagliflozin(MIZA)in autosomal dominant polycystic kidney disease(ADPKD).Methods Western blotting,quantitative polymerase chain reaction(qPCR),and immunofluorescence staining were used to determine the expression and distribution of SGLT1 in kidney tissues of PKD1-/-and PKD1+/+mice,human renal cancer adjacent tissue and ADPKD tissue.Renal cyst lining epithelial cells OX161 and renal tubular epithelial cells UCL93 were treated with MIZA,incubated at 37℃for 24,48,and 72 h,and then were subjected to methyl thiazolyl tetrazolium and colony formation assay to observe cell proliferation.The qPCR method was used to determine the mRNA levels of collagen 1α1,collagen 3α1,and fibronectin 1 in OX161 cells treated with 100 μmol/L MIZA for 48 h.The Madin-Darby canine kidney(MDCK)cell 3D cyst formation assay verified the effect of MIZA on cyst formation.The mRNA-seq technology was used to detect differentially expressed genes between UCL93 cells and OX161 cells,and between OX161 cells and OX161 cells treated with 100 μmol/L MIZA for 48 h,and then the differentially expressed genes were analyzed with Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Results The expression level of SGLT1 was significantly increased in the tissues of ADPKD patients and PKD1-/-mice compared to those in normal kidney tissues(P＜0.05,P＜0.01).Immunofluorescence staining revealed that SGLT1 was mainly expressed in the cystic lining epithelial cells.Additionally,MIZA inhibited the proliferation and fibrosis of polycystic kidney cells in a concentration-and time-dependent manner,and also inhibited cyst formation in 3D formation assay in vitro.The mRNA-seq analysis and KEGG enrichment analysis showed that differentially expressed genes between OX161 cells and OX161 cells cultured in 100 μmol/L MIZA for 48 h were mainly enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)and mitogen-activated protein kinase(MAPK)signaling pathways,which were the same as those between OX161 cells and UCL93 cells.Conclusion The SGLT1 inhibitor MIZA may inhibit the proliferation and fibrosis of polycystic kidney cells through signaling pathways such as PI3K-Akt and MAPK,delaying the growth of polycystic kidney,and it is a potential therapeutic target for ADPKD.

In the context of the digital economy， the operational relationship between traditional Chinese medicine （TCM） and Internet healthcare organizations as well as related governance institutions has attracted much attention. As the market scale of the Internet healthcare has continued to grow in recent years， the quality of Internet TCM healthcare has also been improved. By analyzing the development status of Internet TCM healthcare， it is proposed that Internet TCM health service should seize the opportunities and challenges in future， promote the growth of market scale from varied aspects， enhance patient-centered care awareness， and strengthen the promotion and popularization of digital services， thereby promoting the high-quality development of Internet TCM health service in the context of the digital economy.

Objective:To explore whether barium chloride (BaCl 2) preconditioning has the protective effect on lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) model in mice and the possible mechanism. Methods:Sixty 8-12 week old healthy C57BL/6 male mice were randomly divided into control group, ARDS model group and BaCl 2 pretreatment group, with 20 mice in each group. The BaCl 2 pretreatment group was continuously injected with BaCl 2 (4 mg/kg through the tail vein) for 3 days before ARDS model establishment. ARDS model was established by intratracheally injecting (3 mg/kg) LPS. The control group was intratracheally given the same volume of 0.9% normal saline. On 24th hour after ARDS model establishment, some mice were sacrificed for obtaining fresh lung tissue. And the right lower lobe of the lung was separated for observing the pathological changes of lung tissue while the left lung tissue was used to measure the wet/dry weight ratio (W/D) of the lung. Some mice were sacrificed for observing pulmonary microvascular permeability at 2nd hours after injecting Evans blue (EB) through tail vein. The left mice were killed for alveolar lavage to measure the levels of tumor necrosis factor-α (TNF-α) via enzyme linked immunosorbent assay (ELISA). Results:Comparing with the control group, ARDS model group showed typical ARDS pathological changes, which included the increased W/D ratio (4.951±0.161 vs. 3.449±0.299, P < 0.01) and the content of EB in the lung tissue (μg/g: 0.130±0.027 vs. 0.085±0.011, P < 0.01), the damaged alveolar wall structure, lung congestion and exudates in the alveoli, as well as amounts of inflammatory cells. The pathological score of lung injury (10.33±1.15 vs. 1.67±0.58) and the level of TNF-α in BALF (ng/L: 900.85±247.80 vs. 68.21±5.79) were significantly increased in the ARDS model group (both P < 0.01). Comparing with the ARDS model group, the lung W/D ratio (4.620±0.125 vs. 4.951±0.161) and the EB content in the lung tissue (μg/g: 0.108±0.011 vs. 0.130±0.027) of BaCl 2 pretreatment group were significantly reduced (both P < 0.01). And the damaged pulmonary structural BaCl 2 pretreatment group were significantly alleviated. In addition, the pulmonary pathological score (5.00±1.00 vs. 10.33±1.15) and the level of TNF-α in BALF (ng/L: 169.16±73.33 vs. 900.85±247.80) were significantly decreased (both P < 0.01). Conclusion:Barium chloride pretreatment can improve the lung histopathological changes of ARDS model mice induced by LPS by reducing the permeability of pulmonary capillaries and local inflammatory reaction.Barium chloride has the protective effect against LPS attack in mice model of ARDS.

The most common neurological clinical manifestations of refeeding syndrome(RFS)are seizures and altered consciousness. This article presents a case in which central pontine myelinolysis(CPM) is a complication of RFS and describes its diagnosis and treatment process. This case highlights the importance of early cranial MRI examination to exclude CPM in patients with persistent hypoghosphatemia and altered consciousness during the course of RFS treatment.

Trench foot was first seen in World War Ⅰ and was one of the reasons for non combat attrition. We reviewed and analyzed 15 cases of trench foot admitted from 2010 to 2021, summarized clinical treatment methods and experiences, analyzed the causes, population characteristics, treatment methods, and treatment experiences of trench foot during peacetime, strengthened attention to high-risk groups, and improved the success rate of clinical treatment.