ObjectiveThis study aims to investigate the effect of Liuwei Dihuangwan on the autophagy function in the hippocampus of senescence-accelerated mouse prone 8 （SAMP8） by regulating the expression of glycoprotein non-metastatic melanoma protein B （GPNMB）. Furthermore， it is designed to explore the mechanism of the method of tonifying the kidneys and replenishing essence in the treatment of Alzheimer's disease （AD）. MethodsIn experiment 1， 24 5-month-old SAMP8 mice were randomly and equally divided into the model group， and the low-， middle- and high-dose（0.59，1.18，2.36 g·kg^-1） Liuwei Dihuangwan groups. At the same time， six 5-month-old senescence accelerated mouse resistant 1 （SAMR1） mice were used as the control group. The learning and memory ability was evaluated through novel object recognition experiment. Serum cortisol （Cort）， adrenocorticotropic hormone （ACTH） and urine 17-hydroxycorticosteroid （17-OHCS） levels were detected by enzyme-linked immunosorbent assay （ELISA）. The ultrastructure of hippocampal neurons was observed by transmission electron microscope （TEM）， and the expression levels of hippocampal GPNMB， a disintegrin and metalloproteinase 10 （ADAM10） and autophagy-related proteins were detected by Western blot. In experiment 2， 18 SAMP8 mice were randomly and equally divided into the model group， vector control group （Vector）， and GPNMB overexpression group （GPNMB^OE）. Lentiviral vectors were stereotactically injected into the brain （2 μL per side in the GPNMB^OE group）. Western blot was used to detect the expression of the above target proteins in the hippocampus； In Experiment 3， 24 SAMP8 mice were randomly and equally divided into the model group， Liuwei Dihuangwan group， Liuwei Dihuangwan+negative control （NC） group， and Liuwei Dihuangwan+GPNMB silencing group （shGPNMB）. Before drug treatment， the Liuwei Dihuangwan+NC group and the Liuwei Dihuangwan+shGPNMB group were injected with negative control and GPNMB silencing lentivirus， respectively. Western blot was used to detect the expression of the above target proteins in the hippocampus. ResultsThe novel object discrimination index of mice in the model group was significantly lower than that of mice in the control group （P<0.01）. The novel object discrimination index of mice in the medium- and high-dose Liuwei Dihuangwan groups was significantly higher than that of mice in the model group （P<0.01）. Aggregated autolysosomes were observed in the normal hippocampus tissue by TEM. In the model group， mitochondria were dominant， and no typical characteristic autophagosomes were observed. In the low- and medium-dose Liuwei Dihuangwan groups， a small number of autolysosomes and autophagosomes with double-membrane structures were observed. In the high-dose Liuwei Dihuangwan group， the number of autophagosomes and autolysosomes was greater than that in the low- and medium-dose groups. The results of ELISA and Western blot showed that compared with the control group， the levels of serum Cort， ACTH， and urine 17-OHCS in the model group were substantially increased， while the expression of hippocampal ADAM10， Beclin1， and microtubule associated-protein light chain 3-Ⅱ/Ⅰ （LC3 Ⅱ/Ⅰ） was significantly decreased. The expression of GPNMB and ubiquitin binding protein p62 was significantly increased （P<0.05， P<0.01）. Compared with the model group， the serum Cort and ACTH levels in the low-， medium-， and high-dose Liuwei Dihuangwan groups were significantly reduced， while only the urine 17-OHCS level in the high-dose group was significantly reduced. The hippocampal GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ expression levels in the medium-， and high-dose groups of Liuwei Dihuangwan were significantly increased compared to the model group， whereas the expression of p62 was significantly reduced （P<0.01）. The above indicators showed a progressive trend among the three groups. Compared with the model group， the GPNMB^OE group showed a significant increase in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ expression， and a significant decrease in p62 expression （P<0.01）. Compared with the model group， the expression of GPNMB， ADAM10， Beclin1， and LC3 Ⅱ/Ⅰ in the hippocampus of the Liuwei Dihuangwan group significantly increased， while the expression of p62 significantly decreased （P<0.01）. Compared with the Liuwei Dihuangwan group， the Liuwei Dihuangwan+shGPNMB group showed a significant decrease in GPNMB， ADAM10， Beclin1， LC3 Ⅱ/Ⅰ， and a significant increase in p62 expression （P<0.01）. ConclusionLiuwei Dihuangwan can enhance hippocampal autophagy function and improve AD by upregulating GPNMB expression.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

ObjectiveTo evaluate the efficacy of Shuanghua drink in treating primary dysmenorrhea in the rat model and explore its mechanism of action. MethodsAn oxytocin-induced writhing mouse model was established to evaluate the analgesic effect of Shuanghua drink. Forty-eight non-pregnant female institute of cancer research （ICR） mice were randomly divided into six groups， including a blank group， a model group， an ibuprofen group （85.00 mg·kg^-1）， a low-dose group of Shuanghua drink （7.14 mL·kg^-1）， a medium-dose group of Shuanghua drink （14.28 mL·kg^-1）， and a high-dose group of Shuanghua drink （28.57 mL·kg^-1）. Each group consisted of eight mice. All treatment groups received daily intragastric administration at corresponding doses for 10 consecutive days. One hour after the final administration， 2 U of oxytocin was intraperitoneally injected per mouse. The writhing latency and number of writhing within 20 minutes were recorded. A primary dysmenorrhea rat model was established by using estradiol benzoate and oxytocin to evaluate the inhibitory effect of Shuanghua drink on the contraction of uterine smooth muscle. Forty-eight non-pregnant female Sprague-Dawley （SD） rats were divided into six groups， including a blank group， a model group， an ibuprofen group （51.00 mg·kg^-1）， a low-dose group of Shuanghua drink （4.28 mL·kg^-1）， a medium-dose group of Shuanghua drink （8.57 mL·kg^-1）， and a high-dose group of Shuanghua drink （17.10 mL·kg^-1）. Each group consisted of eight rats. Rats received subcutaneous injections of estradiol benzoate for 10 consecutive days to enhance uterine sensitivity. On the eleventh day， oxytocin （2 U/rat） was intraperitoneally administered to induce abnormal uterine contractions for establishing the primary dysmenorrhea model. All treatment groups received daily intragastric administration from the second day of modeling for 10 days. The effects of Shuanghua drink were evaluated by using parameters including uterine motility and the variation rate of uterine motility. The mechanism of action was investigated in rats with primary dysmenorrhea. The content of prostaglandin F_2α （PGF_2α）， prostaglandin E₂ （PGE₂）， thromboxane B₂ （TXB₂）， prostacyclin metabolite （6-keto-PGF_1α）， and β-endorphin （β-EP） in uterine tissue of rats was detected by using enzyme-linked immunosorbent assay （ELISA）. The changes in the content of nitric oxide （NO） and inducible nitric oxide synthase （iNOS） were analyzed via colorimetric assay. Western blot was performed to determine the content of phosphorylated inhibitor of kappa B kinase beta （p-IKKβ）/IKKβ， phosphorylated inhibitor of kappa B alpha （p-IκBα）， IκBα， phosphorylated p65 （p-p65）， p65， and cyclooxygenase-2 （COX-2） proteins in uterine tissue of rats. ResultsIn the oxytocin-induced writhing mouse model， the model group exhibited significantly shortened writhing latency and increased writhing frequency compared to the control group （P<0.01）. Both the ibuprofen group and the high-dose group of Shuanghua drink displayed prolonged writhing latency （P<0.05）， while the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink exhibited reduced writhing frequency （P<0.01）. In the primary dysmenorrhea rat model， the uterine motility and its variation rate in the model group were significantly higher than those in the blank group （P<0.01）. These parameters were markedly suppressed by ibuprofen and Shuanghua drink at all tested doses （P<0.01）. For the mechanism of action， the model group showed significantly increased PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， NO， and iNOS in uterine tissue （P<0.05， P<0.01） and significantly decreased β-EP （P<0.01）. These parameters were significantly attenuated in the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink. The PGF_2α/PGE₂ （P<0.01）， TXB₂/6-keto-PGF_1α （P<0.01）， NO （medium-dose group P<0.05）， and iNOS （P<0.01） were reduced， and the β-EP （medium-dose group P<0.05） was up-regulated. Compared to the model group， the ibuprofen group and medium-dose group of Shuanghua drink showed significantly increased content of β-EP in the serum of rats （P<0.05）. Compared to the blank group， the model group showed significantly elevated expressions of COX-2， p-IKKβ/IKKβ， p-IκBα/IκBα， and p-p65/p65 proteins （P<0.01） and significantly reduced anti-inflammatory protein IκBα （P<0.05）. Compared to the model group， the ibuprofen group and the low-dose， medium-dose， and high-dose groups of Shuanghua drink showed significantly reduced expressions of COX-2 （P<0.01）， p-IKKβ/IKKβ （P<0.01）， p-IκBα/IκBα （P<0.05， P<0.01）， and p-p65/p65（P<0.01） and up-regulated expression of IκBα protein （P<0.05， P<0.01）. ConclusionShuanghua drink effectively alleviates primary dysmenorrhea through analgesia and suppression of abnormal contractions of uterine smooth muscle. Its mechanism may be mediated by reduced levels of PGF_2α/PGE₂， TXB₂/6-keto-PGF_1α， iNOS， and NO， elevated β-EP level， and inhibited COX-2/NF-κB signaling pathway.

Objective:To develop a scale to measure the sense of gain of the elderly, and to evaluate its reliability and validity.Methods:According to the content of the sense of gain, combined with the literature research method and interview method, the scale entry pool was established.After the expert consistency evaluation and the optimal test assembly method (OTA) analysis, the formal version of the scale was formed.The stratified sampling method was used to select 1 043 community-dwelling elders for the survey, and the reliability and validity of the scale were evaluated by methods based on classical test theory.Results:The scale of elderly sense of gain, which was screened by OTA method, included four dimensions: health status, relationship and communication, social security, and ideal expectation, with a total of 17 items. The Cronbach's α value of the formal version of the scale was 0. 850, and the Cronbach's α coefficients of the four dimensions were 0.721, 0.772, 0.779, and 0.930, respectively. The CR values of the combined reliabilities of each dimension were all above 0.7. In terms of AVE values, except for the health status dimension was acceptable, the other three dimensions were all above 0.36. The correlation coefficient between the sense of health acquisition and life satisfaction of the elderly was 0.531 ( P<0.01). Conclusion:The developed scale for measuring the sense of gain of the elderly has good reliability and validity, which can be used as an effective tool for measuring the sense of gain of the elderly.

AIM:This study aims to investigate distinct patterns in food reward behavior and neuroinflammato-ry responses within the ventral tegmental area(VTA)between obesity-prone(OP)and obesity-resistant(OR)rats,while elucidating their potential interplay.METHODS:Twenty-four male Sprague-Dawley rats(5-week-old)were adminis-tered a high-fat diet(HFD)for 8 weeks.Based on body weight tertiles,rats were stratified into OP(highest tertile,n=8)and OR(lowest tertile,n=8)groups.Food reward function was evaluated through conditioned place preference(CPP)test and operant food-seeking task(OFST).Serum lipid profiles were quantified via colorimetric microplate assays,with 24-hour energy expenditure monitored using CLAMS.Western blot and immunofluorescence assays quantified ionized cal-cium-binding adaptor molecule 1(Iba1)and tyrosine hydroxylase(TH)protein expression,while immunofluorescence lo-calized VTA-positive cell spatial distribution and density.RT-qPCR quantified mRNA expression of Iba1,TH,and proin-flammatory cytokines(TNF-α,IL-1β and IL-6).ELISA quantified proinflammatory cytokine protein concentrations.RE-SULTS:Following 8-week HFD exposure,OP rats exhibited elevated body weight,total food and calories,adiposity,Lee index,and levels of TG,LDL-C,TC,and NEFA,while HLD-C levels and 24-hour energy metabolism significantly decreased(P<0.05).OP rats demonstrated enhanced CPP preference for HFD-paired cues,elevated lever pressing fre-quency,and increased breakpoints versus OR counterparts(P<0.05),positively correlating with body weight(r=0.766,0.561 and 0.606;P<0.05).OP rats demonstrated elevated Iba1 positive cell density,protein and mRNA expression,and inflammatory mediators in VTA versus OR counterparts,contrasting with diminished TH positive neurons showing re-duced protein and mRNA levels(P<0.05).VTA neuroinflammatory mediators(Iba1,TNF-α,IL-1β and IL-6)exhibited inverse correlations with TH protein expression(r=-0.953,-0.866,-0.881 and-0.886;P<0.05).CONCLUSION:The OP rats exhibit attenuated reward sensitivity,elevated HFD preference,and increased palatable food-seeking behavior.These behavioral modifications correlate with VTA neuroinflammation suppressing dopaminergic(DA)biosynthesis.

Allergic conjunctivitis has a high incidence rate, which is difficult to cure after repeated attacks, and seriously affects people's quality of life.Animal models are the main tools and means for the study of allergic conjunctivitis diseases, and animal modeling is an important step in the study of allergic conjunctivitis diseases.Because the study of allergic conjunctivitis is relatively late than that of other allergic diseases, the animal model of allergic conjunctivitis mainly refers to the animal model building methods of allergic asthma, rhinitis and other allergic diseases, or makes improvements on them, resulting in a variety of animal model building methods, poor reference of animal model building methods, and low survival rate and success rate of animal model building.This paper analyzes the pathogenic mechanism of allergic conjunctivitis and the purpose of animal modeling, searches and analyzes the modeling process of allergic conjunctivitis in Pubmed in the past 10 years, sorted and analyzed the modeling methods according to the sensitization mechanism, and summarized four modeling process models, which provided a reference for the selection of animal strains, sensitization dose and sensitization process in the modeling of allergic conjunctivitis.

Objective:To explore the correlation between phase angle, determined by bioelectrical impedance analysis, and common chronic metabolic diseases in centrally obese individuals, aiming to assess the role of phase angle as a potential biomarker in screening for and preventing common chronic metabolic diseases associated with central obesity.Methods:In this retrospectivel study, body composition measurement was conducted among centrally obese patients attending the outpatient clinic of the Department of Clinical Nutrition of the First Affiliated Hospital of Xinjiang Medical University from July 2022 to May 2024, along with the collection of current medical histories. The subjects were divided into three groups from Q1 to Q3 according to the tertiles of phase angle (Q1 group: phase angle<5.1°; Q2 group: phase angle≥5.1° but <5.6°; and Q3 group: phase angle>5.6°), and the prevalence of metabolic diseases and the differences in body compositions were compared among these three groups. Pearson's correlation was used to analyse the potential associations of phase angle and each body composition with common chronic metabolic diseases.Results:A total of 3 476 centrally obese individuals (1 141 males and 2 335 females) were included in the study. The Q1 group had significantly older age [(45.0±15.1) years vs. (36.1±10.0) years], higher prevalence of type 2 diabetes mellitus (T2DM) (23.9% vs. 17.3%), higher body fat percentage [(41.80%±6.36%) vs. (36.81%±7.21%)], and larger visceral fat area [(171.43±43.46) cm2 vs. (157.57±47.05) cm2] but significantly lower body mass index [(29.98±4.93) kg/m2 vs. (32.57±4.94) kg/m2], basal metabolic rate [(5 692.12±653.33) kJ/d vs. (6 809.04±923.49) kJ/d], skeletal muscle index [(7.16±0.86) kg/m2 vs. (8.60±0.94) kg/m2], body cell mass [(29.47±4.63)(38.18±6.70) kg], and waist-to-hip ratio [(0.972±0.069) vs. (0.977±0.063)] than the Q3 group (all P<0.001). However, there were no significant differences in the prevalence rates of hypertension and dyslipidemia among the three groups (all P>0.05). Among female centrally obese patients, those with all three metabolic diseases had significantly smaller phase angle (4.85°±0.54°) than those with 1-2 metabolic diseases (5.10°±0.62°) and those without metabolic diseases (5.17°±0.55°) (both P<0.001). Among T2DM patients receiving different treatment regimens, phase angle was significantly smaller in the insulin treatment group and the combined treatment group than in the lifestyle intervention group and oral hypoglycemic medication group (all P<0.05). Conclusions:Phase angle is an effective indicator of T2DM in centrally obese individuals and has potential clinical value in the screening and evaluation of metabolic diseases in centrally obese individuals.

Objective:To develop a scale to measure the sense of gain of the elderly, and to evaluate its reliability and validity.Methods:According to the content of the sense of gain, combined with the literature research method and interview method, the scale entry pool was established.After the expert consistency evaluation and the optimal test assembly method (OTA) analysis, the formal version of the scale was formed.The stratified sampling method was used to select 1 043 community-dwelling elders for the survey, and the reliability and validity of the scale were evaluated by methods based on classical test theory.Results:The scale of elderly sense of gain, which was screened by OTA method, included four dimensions: health status, relationship and communication, social security, and ideal expectation, with a total of 17 items. The Cronbach's α value of the formal version of the scale was 0. 850, and the Cronbach's α coefficients of the four dimensions were 0.721, 0.772, 0.779, and 0.930, respectively. The CR values of the combined reliabilities of each dimension were all above 0.7. In terms of AVE values, except for the health status dimension was acceptable, the other three dimensions were all above 0.36. The correlation coefficient between the sense of health acquisition and life satisfaction of the elderly was 0.531 ( P<0.01). Conclusion:The developed scale for measuring the sense of gain of the elderly has good reliability and validity, which can be used as an effective tool for measuring the sense of gain of the elderly.

Allergic conjunctivitis has a high incidence rate, which is difficult to cure after repeated attacks, and seriously affects people's quality of life.Animal models are the main tools and means for the study of allergic conjunctivitis diseases, and animal modeling is an important step in the study of allergic conjunctivitis diseases.Because the study of allergic conjunctivitis is relatively late than that of other allergic diseases, the animal model of allergic conjunctivitis mainly refers to the animal model building methods of allergic asthma, rhinitis and other allergic diseases, or makes improvements on them, resulting in a variety of animal model building methods, poor reference of animal model building methods, and low survival rate and success rate of animal model building.This paper analyzes the pathogenic mechanism of allergic conjunctivitis and the purpose of animal modeling, searches and analyzes the modeling process of allergic conjunctivitis in Pubmed in the past 10 years, sorted and analyzed the modeling methods according to the sensitization mechanism, and summarized four modeling process models, which provided a reference for the selection of animal strains, sensitization dose and sensitization process in the modeling of allergic conjunctivitis.