ObjectiveTo observe the effects of modified Chaihu Shugansan on the calmodulin-dependent protein kinase Ⅱ（CaMKⅡ）/cAMP-response element binding protein （CREB） signaling pathway in the hippocampus and heart tissue of a rat model with myocardial ischemia and depression and explore the mechanism by which this formula prevents and treats coronary heart disease combined with depression. MethodsThe model of myocardial ischemia combined with depression was established by high-fat diet， intraperitoneal injection of isoproterenol （ISO）， and chronic unpredictable mild stress （CUMS）. A total of 108 SD male rats were randomly divided into normal group， model group， high （23.4 g·kg^-1）， medium （11.7 g·kg^-1）， and low （5.85 g·kg^-1） dose groups of modified Chaihu Shugansan， CaMKⅡ inhibitor （KN93） group， and KN93 + high， medium， and low dose groups of modified Chaihu Shugansan， with 12 rats in each group. From the first day of modeling to the end of modeling， drugs were administered once a day. In the seventh and eighth weeks， the KN93 group and the KN93 + high， medium， and low dose groups of modified Chaihu Shugansan were intraperitoneally injected with KN93 three times weekly. At the end of the eighth week， behavioral tests including sucrose preference， open field， and elevated plus maze were conducted. Electrocardiogram （ECG） lead Ⅱ changes were observed in each group of rats， and hematoxylin-eosin （HE） staining was performed to observe changes in heart tissue. Serum levels of triglycerides （TG）， total cholesterol （TC）， high-density lipoprotein （HDL）， low-density lipoprotein （LDL）， and lactate dehydrogenase （LDH） were measured by using an enzyme-labeled instrument. Creatine kinase （CK） and creatine kinase-MB （CK-MB） were detected by ultraviolet spectrophotometry， while serum monocyte chemoattractant protein-1 （MCP-1） was measured by enzyme-linked immunosorbent assay （ELISA）. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of CaMKⅡ and CREB in hippocampal and heart tissue， and Western blot was performed to assess protein expression of CaMKⅡ， phosphorylated （p）-CaMKⅡ， CREB， and p-CREB. ResultsCompared to the normal group， the model group showed significant reductions in sucrose preference rate， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）. The ECG showed ST-segment elevation， and HE staining showed serious degeneration of myocardial fibers， disordered arrangement， and infiltration of a large number of inflammatory cells. In addition， serum TC and LDL levels increased （P<0.01）， and HDL level decreased （P<0.01）. CK， CK-MB， LDH， and MCP-1 levels significantly increased （P<0.05， P<0.01）. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB decreased in the hippocampal tissue （P<0.05， P<0.01）， but those increased in the heart tissue （P<0.01）. Compared to the model group， the high， medium， and low dose groups of modified Chaihu Shugansan showed improvements in these abnormalities. The KN93 group had reduced sucrose preference， total activity distance in the open field， number of entries into the center area of the open field， and percentage of entries into the open arms of the elevated plus maze （P<0.01）， as well as decreased serum CK， CK-MB， LDH， and MCP-1 levels （P<0.05， P<0.01）. KN93 also reduced ST-segment elevation， alleviated the degeneration degree of myocardial fibrosis， and lowered inflammatory cell infiltration. The mRNA expression of CaMKⅡ and CREB and the protein expression of p-CaMKⅡ and p-CREB in both the hippocampal and heart tissue were reduced （P<0.05， P<0.01）. The KN93 + high， medium， and low dose groups of modified Chaihu Shugansan showed further improvements in these abnormalities compared to the KN93 group. ConclusionThe modified Chaihu Shugansan exerts antidepressant and myocardial protective effects in rats with myocardial ischemia and depression， possibly related to bidirectional regulation of the CaMKⅡ/CREB signaling pathway， with the high-dose modified Chaihu Shugansan showing the best effects.

Objective: To determine the clinical efficacy of platelet-rich plasma (PRP) injection combined with warm acupuncture and moxibustion for treating patients with knee osteoarthritis and cold dampness obstruction syndrome. Methods: One hundred and twenty-eight patients with knee osteoarthritis and cold dampness obstruction syndrome who visited the Rehabilitation Department and Orthopedics Department of the Second Affiliated Hospital of Anhui University of Chinese Medicine from January 2023 to March 2024 and who met the inclusion and exclusion criteria were randomly divided into an experimental (n=64) and control group (n=64) using the random number table method. The experimental group was treated with PRP injection combined with warm acupuncture and moxibustion, whereas the control group was treated with normal saline injection combined with warm acupuncture and moxibustion treatment. PRP and normal saline injections were administered once every two weeks, a total of four times. Patients were treated with warm acupuncture and moxibustion once a day, six times a week, for four consecutive weeks. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Traditional Chinese Medicine (TCM) syndrome, visual analog scale (VAS), and Lysholm scores were determined before treatment, at week 4 and week 8 of treatment, and week 16 of follow-up. Serum interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), tumor necrosis factor-α (TNF-α), osteoprotegerin (OPG), bone gla protein(BGP), and cartilage oligomeric matrix protein (COMP) levels were compared between the two groups before and after 8 weeks of treatment. The clinical efficacy and safety indicators between the two groups were also compared. Results: There was no statistical difference in baseline data such as gender, age, disease duration, and body mass index between the two groups of patients. Compared with before treatment, both groups showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm scores at 4, 8, and 16 weeks after treatment. After treatment, serum IL-6, MMP-3, TNF-α, and COMP levels decreased, whereas serum OPG and BGP levels increased (P<0.05). Compared with the control group, patients in the experimental group showed decreased WOMAC total and subscale, TCM syndrome total score and symptom scores, and VAS scores, and an increase in Lysholm score at 4, 8, and 16 weeks after treatment. Compared with the control group, patients in the experimental group showed decreased serum IL-6, MMP-3, TNF-α, and COMP levels and an increase in serum OPG and BPG levels after treatment (P<0.05). The total effective rate of the experimental group was 91.94%, higher than that of the control group (81.97%; P<0.05). Conclusion PRP injection combined with warm acupuncture and moxibustion can improve various TCM symptoms, improve knee joint function and bone metabolism, and reduce inflammation in patients with knee osteoarthritis and cold dampness obstruction syndrome.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Aim To establish NCI-H446/EP for small cell lung cancer resistant cells resistant to cisplatin and etoposide, and to evaluate their biological characteristics and multidrug resistance. Methods Nude mice were subcutaneously inoculated with NCI-H446 cells of SCLC to construct an in vivo model of xenograft tumor, and were given first-line EP regimen treatment for SCLC, inducing drug resistance in vivo, and stripping tumor tissue in vitro culture to obtain drug-resistant cells. The resistance coefficient, cell doubling time, cell cycle distribution, expression of multidrug resistance gene (MDR1), and drug resistance-related protein were detected in vitro, and the drug resistance to cisplatin and etoposide in vivo were verified. Results Mice with NCI-H446 tumors acquired resistance after eight weeks' EP regimen treatment, and the drug-resistant cell line NCI-H446/EP was obtained by isolation and culture in vitro. The resistance factors of this cell line to cisplatin, etoposide, SN38 and doxorubicin were 12.01, 18.36, 65.4 and 10.12, respectively. Compared with parental cells, the proportion of NCIH446/EP cells in Q

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Background The staff in centers for disease control and prevention (CDC) were at a great risk for psychological distress when they were faced with outbreak-related prevention and control work and routine tasks during the COVID-19 period. Psychological resilience and burnout are two key influencing factors on psychological distress. Objective To explore the status and mechanisms of psychological resilience, burnout, and psychological distress among CDC staff. Methods From September to October 2022, a cross-sectional survey was conducted in all CDC staff in Beijing, and 2228 CDC staff from 17 units (including 1 municipality-level CDC and 16 district-level CDCs) participated the questionnaire survey. The basic information questionnaire, Connor-Davidson Resilience Scale (CD-RISC-10) Chinese version, Maslach Burnout Inventory-General Survey (MBI-GS) Chinese version, and the 10-item Kessler Psychological Distress Scale (Kessler10) Chinese version were selected in our study. Mann-Whitney U test or Kruskal-Wallis H test was used to analyze the differences in the scores of psychological resilience, burnout, and psychological distress by demographic and sociological characteristics. The correlations among the three elements were analyzed by Spearman correlation analysis. Potential influencing factors of psychological distress of the CDC staff were evaluated by multiple linear regression. A potential mediating effect of psychological resilience-burnout-psychological distress was analyzed by the mediation package of R 4.2.0, and validated by Bootstrap method. Results Of 2228 questionnaires distributed, 2022 valid questionnaires were collected, and the recovery rate was 90.75%. The median (P₂₅, P₇₅) psychological distress score of CDC staff was 13.00 (8.00, 24.00), and the number of participants with psychological distress levels of 1, 2, 3, and 4 was 358 (17.71%), 546 (27.00%), 362 (17.90%), and 756 (37.39%), respectively. The median (P₂₅, P₇₅) psychological resilience score was 24.00 (20.00, 30.00) and the median (P₂₅, P₇₅) burnout score was 38.00 (25.00, 50.00). The results of the multiple linear regression showed that psychological resilience, burnout, caring for the elderly, having a chronic disease, and monthly income had independent influences on psychological distress (P<0.05), and emotional exhaustion, cynicism, and reduced personal accomplishment (reversed) in the case of burnout had a great effect on psychological distress (P<0.05). After controlling general demographic characteristic variables, total burnout score exerted a partial mediation effect on the relationship between psychological resilience and psychological distress, with a mediation effect value of −0.439 (95%CI: −0.483, −0.397), and a total mediation effect contribution rate of 60.89%. The two dimensions of burnout (emotional exhaustion and cynicism) played a partial mediating role between psychological resilience and psychological distress, with mediating effect contribution rates of 42.44% and 41.41%, respectively. Conclusion Psychological distress among CDC staff in Beijing was prominent during COVID-19. Psychological resilience can act directly on psychological distress or indirectly on psychological distress through burnout. Both emotional exhaustion and cynicism dimensions of burnout have a partial mediating role between psychological resilience and psychological distress. Increasing psychological resilience and decreasing burnout may reduce the occurrence of psychological distress.

Objective To study the application effect of quality control circle(QCC)in reducing the dissatisfaction rate of physical examination clients in health management center.Methods To establish QCC,selected the health check-up popula-tion in our hospital in September-2019 and March-2020,through the questionnaire investigation and analysis,compare the dis-satisfaction of the clients before and after the quality control circle.Results After carrying out QCC activities,the dissatisfaction of physical examination clients was significantly lower than that before QCC,and the difference was statistically significant(P＜0.05).Conclusion The activities of QCC in the health management center can effectively improve the quality of the physical examination work and reduce the dissatisfaction of the customers in the physical examination.It is of great significance to the health management.

Objective : To analyze the difference of urinary iodine level in Hashimoto thyroiditis ( HT) patients， and to explore the possible relationship between urinary iodine level and HT under different iodine nutritional sta- tus，so as to provide some references for reasonable iodine intake in HT patients． Methods : A total of 101 hospi- talized HT patients were selected as HT group and divided into 3 groups according to thyroid function : HT group with hyperthyroidism (41 cases) ．There were 25 cases in HT group with normal thyroid function．There were 35 cases in HT combined with hypothyroidism group．In addition，30 healthy subjects were selected as control group. Serum levels of thyroid stimulating hormone(TSH) ，triiodothyronine(T3 ) ，thyroxine (T4 ) ，thyroid peroxidase an- tibody (TPOAb) and thyroglobulin antibody (ATG) were detected by chemiluminescence assay．The size and mor- phological structure of thyroid organs were examined by ultrasonography．Urinary iodine was determined by catalytic spectrophotometry with arsenic and cerium．The nutritional status of iodine was classified into iodine deficiency ( < 100 μg/ L) ，iodine adequacy( 100 －199 μg/ L) ，iodine adequacy (200 －299 μg/ L) and iodine excess ( ≥ 300 μg/ L) ．Non-parametric test was used to compare urinary iodine level between HT group and control group，one- way ANOVA and t test were used to compare urinary iodine level between HT group and control group ，and Spearman correlation analysis was used to compare the correlation between urinary iodine level and T3 ，T4 ，TSH， ATG and TPOAb under different iodine nutrition status. Results : Compared with control group，ATG and TPOAb levels in HT group increased (P＜0. 001) ，and urinary iodine levels increased (P＜0. 05) ，with statistical signifi- cance．Compared with the control group in different thyroid function states，only the HT group with hypothyroidism increased the urinary iodine level (P＜0. 01) ，and the difference was statistically significant．Spearman correlation analysis showed that urine iodine level was positively correlated with ATG and TPOAb levels in iodine excess condi- tion (P＜0. 05) ，and urine iodine level was positively correlated with TSH level in iodine sufficient condition and iodine excess condition in HT patients (P＜0. 05) ． Conclusion The urinary iodine level of HT patients was high- er than that of normal people．When the urinary iodine level of residents is ≥ 300 μg/ L，iodine intake is prone to HT．When the urinary iodine level of HT patients is ≥ 200 μg/ L，iodine consumption is prone to hypothyroidism， and iodine intake should be limited.

AIM:To establish a model of meibomian gland dysfunction in rats induced by eyeliner tattoo and investigate its potential mechanisms.METHODS:A total of 40 SD rats were selected, with 30 randomly chosen to have eyeliner tattoo applied their right eyes and designated as the eyeliner group. The remaining 10 rats were not given any treatment and served as the normal group. The corneal morphology of both groups was observed using a slit lamp at 1, 2, and 4 wk after establishment, and the tear film break-up time(BUT), Schirmer I test(SIt), corneal fluorescein staining score, and corneal irregularity score were calculated. The corneal Placido rings were examined using an ocular surface analyzer, and the corneal tissue structures of both groups were observed under a confocal microscope. After 4 wk and completion of clinical indicator recording, the eyeballs and upper and lower eyelid tissues were taken for pathological examination. The meibomian gland structures were observed through HE staining, the conjunctival goblet cells were observed using PAS staining, and the lipid droplets were observed with ORO staining.RESULTS:The slit lamp examination results showed that the eyeliner group rats exhibited in situ black pigmentation in the eyelids, with no eyelid deformation or scarring. The corneal epithelium was rough, with positive fluorescein staining, presenting as spotty staining that worsened over time. Compared with the normal group, the BUT was significantly shortened, tear secretion volume was significantly decreased, and the corneal fluorescein staining score and corneal irregularity score were significantly increased at 1, 2, and 4 wk after modeling in the eyeliner group(all P<0.01). The corneal confocal microscopy results showed a decrease in corneal epithelial cells in the eyeliner group, with the appearance of abnormally bright cells, and inflammatory cell infiltration visible in the stromal layer. The ORO staining results revealed a decrease in lipid droplets in the eyeliner group, showing a downward trend with increasing observation time. The HE staining results showed that pigment blocked the meibomian gland openings in the eyeliner group, and the density of meibomian gland acini showed a downward trend over time. The PAS staining results showed a decreasing trend in the number of PAS-positive cells in the eyeliner group.CONCLUSION:Eyeliner tattoo can induce meibomian gland dysfunction, and the blockage of meibomian gland openings caused by the pigment particles used may be an important cause of meibomian gland dysfunction.

Objective To evaluate the bioequivalence and safety of ibuprofen arginine granules test and reference formulations in Chinese healthy volunteers under fasting and postprandial conditions,and to provide evidence for consistency evaluation and clinical application of the drugs.Methods A single-center,single-dose,randomized,open-label,fasting and postprandial,two-period,two-crossover trial design was used.Twenty-four healthy Chinese volunteers were enrolled in the fasting and postprandial trial,respectively.The test preparation and reference preparation of ibuprofen arginine granules 0.4 g were taken orally in a randomized crossover single dose.Data analysis was performed using Phoenix WinNonlin 8.3.Results In the fasting group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(51.07±7.43)and(50.10±7.64)μg·mL-1;AUC0-,were(122.78±20.62)and(119.94±21.03)μg·h·mL-1;AUC0_∞ were(125.84±21.31)and(122.64±21.87)μg·h·mL-1,respectively.In the postprandial group,the main pharmacokinetic parameters of ibuprofen in plasma after administration of the test and reference formulations of ibuprofen arginine granules were as follows:Cmax were(17.47±3.56)and(17.89±4.47)μg·mL-1;AUC0-twere(114.33±17.12)and(122.13±29.46)μg·h·mL-1;AUC0_∞ were(134.04±36.72)and(133.96±30.35)μg·h·mL-1,respectively.The 90％confidence intervals of the geometric mean ratio of the two preparations were as follows:Cmax 97.96％-106.02％,AUC0_t 98.77％-105.14％,AUC0-∞ 99.34％-105.19％in fasting group;in postprandial group,Cmax was 92.37％-103.05％,AUC0-t was 93.31％-99.56％,AUC0-∞ was 93.89％-102.91％.Conclusion The test preparation and reference preparation of ibuprofen arginine granules in this study are bioequivalent in healthy adult Chinese volunteers.