ObjectiveTo investigate the effect of Danggui Shaoyaosan on the expression of Toll-like receptor 4/nuclear factor-kappa B p65/NOD-like receptor protein 3 （TLR4/NF-κB p65/NLRP3） signaling pathway in the renal tissues of db/db mice with spontaneous diabetes， and to explore the potential mechanism by which Danggui Shaoyaosan alleviates inflammation in diabetic kidney disease （DKD）. MethodsThirty db/db mice were divided into five groups： A model group， Danggui Shaoyaosan low- （16.77 g·kg^-1·d^-1）， medium- （33.54 g·kg^-1·d^-1）， and high-dose （67.08 g·kg^-1·d^-1） intervention groups， as well as an irbesartan group （0.025 g·kg^-1·d^-1） by the random number table method， with 6 mice in each group. Additionally， 6 db/m mice were assigned to the normal group. After 8 weeks of intervention， the following parameters were determined by corresponding methods： body weight， fasting blood glucose （FBG）， 24-hour urinary protein （24 h-UTP）， and serum creatinine （SCr） levels， renal histopathological analysis by hematoxylin-eosin （HE） staining， Masson staining， and periodic acid-Schiff （PAS） staining， the protein and mRNA expression levels of TLR4， NF-κB p65， NLRP3， tumor necrosis factor-alpha （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， interleukin-10 （IL-10）， and interleukin-18 （IL-18） by Western blot and Real-time quantitative polymerase chain reaction （Real-time PCR）， as well as TLR4， NF-κB p65， and NLRP3 protein expression in renal tissues by immunohistochemistry （IHC）. ResultsCompared with the normal group， the model group exhibited increased body weight， FBG， 24 h-UTP， and SCr levels （P<0.05）； disordered renal structure， thickened basement membrane， and interstitial inflammatory cell infiltration， elevated TLR4， NF-κB p65， NLRP3， TNF-α， IL-1β， IL-6， and IL-18 expression； as well as decreased IL-10 expression （P<0.05）. Compared with the model group， these pathological changes and biochemical abnormalities were reversed in the medicine intervention groups to varying degrees （P<0.05）. ConclusionDanggui Shaoyaosan may delay DKD progression by alleviating renal inflammatory response and reducing urinary protein excretion via modulating the TLR4/NF-κB p65/NLRP3 signaling pathway.

Objective: To investigate the protective effects and mechanisms of acellular nerve allografts (ANA) on motor neurons in the spinal cord anterior horn of sciatic nerve injury ( SNI) rats . Methods: SPF grade male SD rats were randomly divided into normal , model , ANA-bridged (bridge group) , and autologous nerve transplantation groups (autograft group) , with 6 rats in each group . The SNI rat model was established using the right sciatic nerve clamp method for 10 mm . In the bridge group , the ANA was bridged to the two severed ends of the injured sciatic nerve , and in the autograft group , the autologous nerves were flipped head to tail and then bridged to the two se- vered ends . A spectrophotometer was applied to determine the DNA content in normal nerves and ANA . The foot- print test was used to determine the sciatic nerve function index (SFI) of the rats in each group , the wet weight ra- tio of the anterior tibialis muscle was calculated . The morphology and structure of the anterior horn motor neurons of the spinal cord of each group were observed by HE staining. The immunofluorescence and Western blot were used to detect Apaf-1 , Caspase-3 , Bcl-2 , Bax , and Cyt-C proteins expression in the L4-6 segment of the spinal cord . Results: The DNA content in the ANA prepared in this study was significantly lower than that in normal nerves (P < 0. 05) . Compared with the normal group , the SFI and wet weight ratio of the anterior tibialis muscle were re- duced in the model group (P < 0. 001) ; compared with the model group , both SFI and wet weight ratio of the ante- rior tibialis muscle significantly increased in the bridge group and the autografts group ( P < 0. 05 , P < 0. 001) , and the SFI and wet weight ratio of the anterior tibialis muscle in the autograft group were higher than those in the bridge group (P < 0. 001 , P < 0. 01) . The results of HE staining showed that the motor neurons in the anterior horn of the spinal cord of the normal group were structurally intact and had clear cytosolic boundaries; the neurons in the model group were lysed and necrotic , with blurred cytosolic boundaries; the neurons in the bridge group were less lysed and necrotic , but the nuclear translocation phenomenon could still be seen; the neurons in the autograft group were morphologically and structurally intact with clear cytosolic boundaries . Compared with the normal group , the expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins significantly increased in the model group (P < 0. 001 , P < 0. 01 , P < 0. 01 , P < 0. 05) . Compared with the model group , the expression of Apaf-1 , Caspase- 3 , Bax , and Cyt-C proteins significantly decreased (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) ; but the expres- sion of Bcl-2 protein significantly increased in the bridge group and the autograft group (P < 0. 05) . The expression of Apaf-1 , Caspase-3 , Bax and Cyt-C proteins in the autografts group was lower than that in the bridge group (P < 0. 001 , P < 0. 05 , P < 0. 05 , P < 0. 05) . Conclusion ANA can exert a protective effect on motor neurons in the anterior horn of the spinal cord of SNI rats by improving the morphology and structure of neurons , increasing the ex- pression of Bcl-2 protein , but decreasing the expression of Cyt-C , Bax , Caspase-3 , and Apaf-1 proteins in the spi- nal cord . The mechanism of ANA may be related to the Bcl-2/Cyt-C/Apaf-1-mediated mitochondrial apoptosis sig- naling pathway .

Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P＜0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P＜0.05),fecal water content was lower(P＜0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P＜0.05);Lower pain threshold(P＜0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P＜0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P＜0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35％),organic acids and derivatives(22.8％),and organoheterocyclic compounds(15.79％).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective:To investigate the relationship between nerve growth factor (NGF) concentration in follicular fluid and abnormal menstrual cycle in infertile patients with polycystic ovary syndrome (PCOS).Methods:A retrospective cohort study was conducted on 100 infertile patients with PCOS who underwent in vitro fertilization and embryo transfer (IVF-ET) at Department of Obstetrics and Gynecology, Peking University Third Hospital from March 2017 to June 2019. For comparison, the 100 patients with PCOS were divided into low NGF group ( n=50) and high NGF group ( n=50) based on the median NGF concentration (1 644.03 ng/L) in follicular fluid. Baseline characteristics, menstrual status and clinical outcomes of assisted reproductive technology were compared. We performed multiple linear regression analysis to examine the effect of NGF in follicular fluid on menstrual cycle length for multivariate analysis. Results:1) PCOS patients in the low NGF group had significantly higher body mass index [(27.24±5.17) kg/m 2] and white blood cell count [7.31(5.99, 8.43)×10 9/L ] than those in the high NGF group [(25.03±4.46) kg/m 2, P=0.024; 5.95(5.08,7.01)×10 9/L, P=0.001], while high-density lipoprotein cholesterol [1.15 (0.98, 1.36) mmol/L] and basic follicle-stimulating hormone level [6.51 (5.10,7.95) U/L] in the low NGF group were significantly lower than those in the high NGF group [1.36 (1.09,1.52) mmol/L, P=0.039;6.51 (5.10,7.95)U/L, P=0.040]. 2) PCOS patients in the low NGF group had significantly higher menstrual cycle length [60.00 (35.00, 180.00) d] than the high NGF group [32.50 (27.00,67.50) d, P=0.001]. 3) Multiple linear regression analysis revealed that after adjustment for body mass index, age, infertility duration, infertility type, and glucose and lipid metabolic parameters, the NGF concentration in the follicular fluid independently and negatively correlated with menstrual cycle length ( P<0.05). 4) The NGF concentration in follicular fluid was not correlated with assisted reproductive outcomes. Conclusion:NGF concentration in follicular fluid is closely related to the degree of menstrual cycle abnormalities in patients with PCOS.

Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P＜0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P＜0.05),fecal water content was lower(P＜0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P＜0.05);Lower pain threshold(P＜0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P＜0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P＜0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35％),organic acids and derivatives(22.8％),and organoheterocyclic compounds(15.79％).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.

OBJECTIVE To analyze the cost-effectiveness of abemaciclib， palbociclib and ribociclib combined with aromatase inhibitors （AI） in first-line treatment of hormone receptor-positive （HR+） advanced breast cancer from the perspective of Chinese medical system. METHODS The 20-year disease course of the patients was simulated by the partitioned survival model， and the simulation period was determined to be 4 weeks， the model output was the total cost and quality-adjusted life year （QALY）， the cost and effect were discounted at a discount rate of 5%. A network meta-analysis was constructed by systematically searching relevant clinical trials to obtain the efficacy parameters of abemaciclib， palbociclib and ribociclib combined with AI. Survival fitting and extrapolation were performed based on the survival curve of the placebo group in MONALEESA-2 trial. Cost-effectiveness was assessed by incremental cost-effectiveness ratio （ICER） and incremental net monetary benefit （INMB）， with a willingness-to-pay threshold of 3 times China’s per capita gross domestic product （GDP） in 2023； one-way sensitivity analysis and probability sensitivity analysis were used to detect the influence of parameters on the results and the robustness of the incremental analysis results. RESULTS In the 20-year simulation， compared with palbociclib+AI scheme， the ICER of ribociclib+AI scheme was 58 558.38 yuan/QALY and the INMB was 62 988.20 yuan. Compared with ribociclib+AI scheme， the ICER of abemaciclib+AI scheme was 264 928.34 yuan/QALY and the INMB was 344.84 yuan. One-way sensitivity analysis showed that the incremental analysis results of abemaciclib+AI scheme compared to ribociclib+AI scheme were not robust. Probabilistic sensitivity analysis confirmed that the probability of ribociclib+AI scheme becoming the most economical was the highest when the threshold was 1-3 times China’s per capita GDP in 2023. CONCLUSIONS Ribociclib+AI scheme is more likely to be the most economical first-line treatment than abemaciclib+AI scheme and palbociclib+AI scheme in Chinese patients with HR+ advanced breast cancer when threshold is 1-3 times China’s per capita GDP in 2023.

ObjectiveTo investigate the effect and mechanism of Zhenwutang on renal oxidative damage in the mouse model of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency via the nuclear factor erythroid 2-related factor-2 （Nrf2）/heme oxygenase-1 （HO-1）/glutathione peroxidase 4 （GPX4） signaling pathway. MethodTwenty-five 7-week-old SPF-grade male db/m mice and 95 7-week-old SPF-grade male db/db mice were adaptively fed for a week. A blank group was set with the db/m mice without treatment， and the other mice were administrated with Rhei Radix et Rhizoma decoction and hydrocortisone for the modeling of diabetic kidney disease with the syndrome of spleen-kidney Yang deficiency. The modeled mice were randomized into the model， irbesartan （25 mg·kg^-1）， and high-， medium-， low-dose （33.8， 16.9， 8.45 g·kg^-1） Zhenwutang groups （n=15） and administrated with corresponding drugs for 8 weeks. The survival status of mice was observed， and the traditional Chinese medicine （TCM） syndrome score was recorded. The indicators related to spleen-kidney Yang deficiency， fasting blood glucose （FBG）， and renal function indicators were determined. Hematoxylin-eosin staining was employed to observe the histopathological changes of the renal tissue in each group. Biochemical kits were used to determine the oxidative stress-related indicators in the renal tissue. Real-time polymerase chain reaction and Western blotting were employed to determine the mRNA and protein levels， respectively， of Nrf2， HO-1， glutamate-cysteine ligase catalytic subunit （GCLC）， and GPX4 in the renal tissue of mice in each group. ResultCompared with the blank group， the modeling increased the TCM syndrome score （P<0.05）， elevated the estradiol （E₂） and FBG levels （P<0.05）， lowered the testosterone （T）， triiodothyronine （T3）， and tetraiodothyronine （T4） levels （P<0.05）， and weakened the renal function （P<0.05）. In addition， the modeling led to glomerular hypertrophy and glomerular mesangial and basal thickening， decreased the catalase （CAT） activity， total antioxidant capacity （T-AOC）， and glutathione （GSH） content （P<0.05）， increased the malondialdehyde （MDA） content （P<0.05）， and down-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. Compared with the model group， high and medium doses of Zhenwutang decreased the TCM syndrome score and E₂ content （P<0.05）， increased the T， T3， and T4 content （P<0.05）， improved the renal function （P<0.05）， alleviated the pathological changes in the renal tissue， increased CAT， T-AOC， and GSH （P<0.05）， reduced MDA （P<0.05）， and up-regulated the mRNA and protein levels of Nrf2， HO-1， GCLC， and GPX4 in the renal tissue （P<0.05）. ConclusionZhenwutang can improve the general state and renal function and reduce the oxidative damage and pathological changes in the renal tissue of db/db mice with spleen-kidney Yang deficiency by regulating the Nrf2/HO-1/GPX4 signaling pathway.

Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.

Reading is an important way for acquiring knowledge,enhancing humanistic literacy,and alleviating negative moods.This paper,based on a survey of the reading habits of medical staff at a public hospital with 1 508 valid samples,found that the reading preferences were closely associated with factors such as educational background,age,job position,gender,and length of service.Drawing from these insights,this paper proposed recommendations to improve the quantity and quality of read-ing among medical professionals.Additionally,suggestions were made for the construction of a humanistic environment and cul-tural development within public hospitals,aiming to foster a favorable cultural atmosphere and enhance the humanistic care pro-vided to patients.