ObjectiveTo elucidate the correlation between alterations in digestion and absorption functions and hepatic deficiency states in aging rats based on the R-spondin1/Wnt3a signaling pathway， and reveal the intervention mechanism of Bugansan. MethodsForty-eight SPF-grade male SD rats were randomly assigned to six groups： blank control， model， low-， medium-， and high-dose （7.03， 14.06， 28.12 g·kg^-1， respectively） Bugansan， and vitamin E （suspension， 27 mg·kg^-1）， with 8 rats in each group. The rat model of aging was established by intraperitoneal injection of D-galactose （400 mg·kg^-1）， while the blank control group was injected with normal saline. Since the day of modeling， rats in intervention groups received corresponding agents by gavage， and those in blank control and model groups received an equal volume of normal saline （10 mL·kg^-1）. General biological features such as fur color， activity， body mass， water intake， and food intake were observed. Meanwhile， the content of malondialdehyde （MDA） and the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH-Px） in the serum were measured to assess aging. Grip strength and the content of total bile acids （TBA） and the activity of α-amylase （AMY） in the serum were measured to evaluate hepatic deficiency states. The activity of β-galactosidase （β-gal） in the duodenum was measured to evaluate intestinal senescence. The levels of glucagon-like peptide-1 （GLP-1）， vasoactive intestinal peptide （VIP）， and D-xylose in the serum were determined to assess digestion and absorption functions of the small intestine. Hematoxylin-eosin staining was conducted to observe pathological changes of the duodenum to assess the small intestine damage. Immunohistochemical staining was employed to visualize the expression of B-cell-specific Moloney murine leukemia virus integration site 1 （Bmi1） and leucine-rich repeat-containing G protein-coupled receptor 5 （Lgr5） in the duodenal tissue. Moreover， Real-time quantitative polymerase chain reaction （Real-time PCR） was utilized to quantify the mRNA levels of Ki67， Bmi1， and Lgr5 to assess proliferation and regeneration of the small intestine. Additionally， the mRNA levels of R-spondin1， Wnt3a， β-catenin， and glycogen synthase kinase-3β （GSK-3β） and the protein levels of R-spondin1， Wnt3a， β-catenin， and phosphorylated GSK-3β （p-GSK-3β） in the duodenum were determined by Real-time PCR and Western blot， respectively， to analyze the mechanisms of intestinal digestion and absorption dysfunction in aging rats and the regulatory characteristics of Bugansan. ResultsCompared with blank control group， the model group showed decreases in body mass， water intake， food intake， grip strength， activities of SOD， GSH-Px， and AMY in the serum and content of GLP-1， VIP and D-xylose in the serum （P<0.05）， increases in the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）， reductions in villus length， villus width， crypt depth， and villi/crypt （V/C） value， down-regulated mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and up-regulated level of GSK-3β， phosphorylation （p）-GSK-3β （P<0.05）. Compared with the model group， Bugansan increased the body mass， water intake， food intake， grip strength， and activities of SOD， GSH-Px， and AMY and levels of GLP-1， VIP and D-xylose in the serum （P<0.05）， while decreasing the content of MDA and TBA in the serum and β-gal activity in the duodenum （P<0.05）. Furthermore， Bugansan increased the villus length， villus width， crypt depth， and V/C value， up-regulated the mRNA and protein levels of Ki67， Lgr5， Bmi1， R-spondin1， Wnt3a， β-catenin， and down-regulated the level of GSK-3β and p-GSK-3β （P<0.05）. ConclusionAging rats exhibit obvious impairments in digestion and absorption functions， accompanied by a state of hepatic deficiency. The traditional Chinese medicine approach of tonifying liver Qi effectively ameliorates aging-related changes by modulating the R-spondin1/Wnt3a signaling pathway to mitigate intestinal senescence and enhance digestion and absorption functions， ultimately contributing to the delay of aging.

This study explores whether the current external quality assessment (EQA) level and acceptable bias for basic semen analysis in China are clinically useful. We collected data of semen EQA from Andrology laboratories in the Hunan Province (China) in 2022 and searched for data in the published literature from January 2000 to December 2023 in China. On the basis of these data, we analyzed the coefficients of variation and acceptable biases of different quality control materials for basic semen analysis through robust statistics. We compared these findings with quality specifications based on biological variation from optimal, desirable, and minimum levels of bias to seek a unified and more suitable semen EQA bias evaluation standard for China's national conditions. Different sources of semen quality control material exhibited considerable variation in acceptable biases among laboratories, ranging from 8.2% to 56.9%. A total of 50.0% of the laboratories met the minimum quality specifications for progressive motility (PR), whereas 100.0% and 75.0% of laboratories met only the minimum quality specifications for sperm concentration and total motility (nonprogressive [NP] + PR), respectively. The Z value for sperm concentration and PR+NP was equivalent to the desirable performance specification, whereas the Z value for PR was equivalent only to the minimum performance specification. This study highlights the feasibility of operating external quality assessment schemes for basic semen analysis using quality specifications based on biological variation. These specifications should be unified among external quality control (EQC) centers based on biological variation.
Semen Analysis/standards* ; Humans ; China ; Male ; Quality Control ; Sperm Motility ; Sperm Count/standards*

Pelvic organ prolapse (POP), whose etiology is influenced by genetic and clinical risk factors, considerably impacts women's quality of life. However, the genetic underpinnings in non-European populations and comprehensive risk models integrating genetic and clinical factors remain underexplored. This study constructed the first polygenic risk score (PRS) for POP in the Chinese population by utilizing 20 disease-associated variants from the largest existing genome-wide association study. We analyzed a discovery cohort of 576 cases and 623 controls and a validation cohort of 264 cases and 200 controls. Results showed that the case group exhibited a significantly higher PRS than the control group. Moreover, the odds ratio of the top 10% risk group was 2.6 times higher than that of the bottom 10%. A high PRS was significantly correlated with POP occurrence in women older than 50 years old and in those with one or no childbirths. As far as we know, the integrated prediction model, which combined PRS and clinical risk factors, demonstrated better predictive accuracy than other existing PRS models. This combined risk assessment model serves as a robust tool for POP risk prediction and stratification, thereby offering insights into individualized preventive measures and treatment strategies in future clinical practice.
Humans ; Female ; Pelvic Organ Prolapse/epidemiology* ; Middle Aged ; Risk Assessment/methods* ; China/epidemiology* ; Multifactorial Inheritance ; Aged ; Risk Factors ; Genome-Wide Association Study ; Genetic Predisposition to Disease ; Case-Control Studies ; Adult ; Polymorphism, Single Nucleotide ; Genetic Risk Score ; East Asian People

OBJECTIVE: Varied acupoint selections represent a potential cause of the uncertainty surrounding the efficacy of acupuncture for knee osteoarthritis (OA). Skin temperature, a guiding factor for acupoint selection, may help to address this issue. This study explored thermal sensitization of acupoints used for the treatment of knee OA. METHODS: This cross-sectional case-control study enrolled cases aged 45-75 years with symptomatic knee OA and age- and gender-matched non-knee OA controls in a 1:1 ratio. All participants underwent infrared thermographic imaging. The primary outcome was the relative skin temperature of acupoint (STA), and the secondary outcome was the absolute STA of 11 acupoints. The Z test was used to compare the relative and absolute STAs between the groups. Principal component analysis was used to extract the common factors (CFs, acupoint cluster) in the STAs. A general linear model was used to identify factors affecting the STA in the knee OA cases. For the group comparisons of relative STA, P < 0.0045 (adjusted for 11 acupoints through Bonferroni correction) was considered to indicate statistical significance. For other analyses, P < 0.05 was used as the threshold for statistical significance. RESULTS: The analysis included 308 participants, consisting of 151 cases (mean age: [64.58 ± 6.67] years; male: 25.83%; mean body mass index: [25.70 ± 3.16] kg/m²) and 157 controls (mean age: [63.37 ± 5.96] years; male: 26.11%; mean body mass index: [24.47 ± 2.84] kg/m²). The relative STAs of ST34 (P = 0.0001), EX-LE2 (P < 0.0001), EX-LE5 (P = 0.0006), SP10 (P < 0.0001), BL40 (P = 0.0012) and GB39 (P = 0.0037) were higher in the knee OA group. No difference was found in the STAs of ST35, ST36, SP9, GB33 and GB34. Four CFs were identified for relative STA in both groups. The acupoints within each CF were consistent between the groups. The mean values of the relative STAs across each CF were higher in the knee OA group. In the knee OA cases, no factors were observed to affect the relative STA, while age and gender were found to affect the absolute STA. CONCLUSION Among patients with knee OA, thermal sensitization occurs in the acupoints of the lower extremity, exhibiting localized and regional thermal consistencies. The thermally sensitized acupoints that we identified in this study, ST34, SP10, EX-LE2, EX-LE5, GB39 and BL40, may be good choices for the acupuncture treatment of knee OA. Please cite this article as: Tu JF, Wang XZ, Yan SY, Wang YR, Yang JW, Shi GX, Zhang WZ, Jing LN, Yang LS, Liu DH, Wang LQ, Mi BH. Thermal sensitization of acupoints in patients with knee osteoarthritis: A cross-sectional case-control study. J Integr Med. 2025; 23(3): 289-296.
Humans ; Osteoarthritis, Knee/physiopathology* ; Male ; Cross-Sectional Studies ; Middle Aged ; Female ; Acupuncture Points ; Case-Control Studies ; Aged ; Skin Temperature ; Acupuncture Therapy

The PIF7 gene is a member of the bHLH family, playing a pivotal role in plant germination. However, its roles in tea plants (Camellia sinensis) remain largely unexplored. In this study, we cloned the phytochrome-interacting factor gene CsPIF7 to elucidate its role in the germination of tea plants. Subcellular localization analysis demonstrated that CsPIF7 was localized in the nucleus. Yeast one-hybrid and dual-luciferase reporter assays demonstrated that CsPIF7 directly bound to a specific region (7-321 bp) of the CsEXP promoter, thereby repressing the expression of CsEXP. These findings suggest that CsPIF7 may modulate the germination of tea plants by inhibiting the expression of CsEXP. Quantitative real-time PCR results showed that both CsPIF7 and CsEXP exhibited high expression levels in tea buds, with different expression patterns in response to abscisic acid (ABA) treatment. Furthermore, both CsPIF7 and CsEXP were upregulated under cold stress at 4 ℃, indicating their involvement in the cold response of tea plants. Taken together, these results suggest that CsPIF7 regulates CsEXP expression in an ABA-dependent manner, thereby influencing the germination of tea plants. This study provides both theoretical and experimental insights into the molecular mechanisms governing the germination of tea plants, laying the groundwork for further exploring the role of PIF7 in plant development and stress responses.
Camellia sinensis/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Abscisic Acid/pharmacology* ; Germination/genetics* ; Basic Helix-Loop-Helix Transcription Factors/metabolism* ; Promoter Regions, Genetic ; Cold Temperature

Objective:To develop a task-oriented exercise(TOE)program suitable for hospitalized elderly frailty patients, and to evaluate its effects on patients' upper and lower limb mobility and activities of daily living.Methods:Using the convenience sampling method, 60 elderly frailty patients admitted to Beijing Hospital between August and December 2019 were selected and randomly divided into a TOE group and a conventional care group, with 30 in each group.In addition to conventional treatment and care, the TOE group performed task-oriented training(turning to fetch objects and multidirectional stepping), while the conventional care group performed aerobic training and resistance training.Both groups completed 10 training sessions.Baseline data of patients in both groups were assessed before intervention.Grip strength(as a measure of upper limb motor function), the motor component of the World Health Organization disability assessment schedule(WHODAS)2.0(as a measure of lower limb motor function), and the modified Barthel index(as measure of the ability to perform activities of daily living)were assessed after intervention.Results:Before intervention, the grip strength values of the TOE group and the conventional care group were(20.21±6.39)kg and(17.61±10.59)kg, and the scores of the motor component of WHODAS 2.0 were(16.07±6.64)and(20.23±1.18), respectively.After intervention, the grip strength value and the score of the motor component of WHODAS 2.0 of the TOE group were(22.13±5.97)kg and(12.86±5.17)kg, respectively, with statistically significant differences compared with those of the conventional care group, which were(19.05±9.16)kg for grip strength and(15.67±1.11)for the motor component of WHODAS 2.0( t=2.005, P=0.049; t=-18.210, P<0.001).The value of grip strength and the score of the motor component of WHODAS 2.0 were higher post-intervention than pre-intervention in the TOE group( t=5.005、-5.291, P<0.001 for both), but they showed no statistical differences in the conventional care group( t=0.247、1.614, P=0.806, 0.112).After intervention, the total modified Barthel index scores of the TOE and conventional care groups were (55.27±37.12)and(57.27±33.39), respectively, higher than the pre-intervention scores, which were(42.27±29.92)and(40.54±20.55), respectively(both P<0.05).There was no statistical difference in total Barthel score between the two groups after intervention( t=1.042, P=0.303). Conclusions:For hospitalized elderly frailty patients, the TOE program is simple, easy to implement, safe and effective, and can not only achieve the same purpose of improving the ability to perform activities of daily living as the conventional exercise program, but also improve the performance of upper and lower limb motor function more quickly.

Background The senescence of alveolar type II epithelial cells is an important driving factor for the progression of silicotic fibrosis, and the regulatory effects of oxamate on the senescence of alveolar type II epithelial cells is still unclear. Objective To explore whether lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting senescence of alveolar type II epithelial cellsMethods This study was divided into two parts: in vivo experiments and in vitro experiments. In the first part, forty SPF C57BL/6J male mice were randomly divided into four groups with 10 in each group: control group, silicosis model group, low-dose oxamate treatment group, and high-dose oxamate treatment group. The silicotic mouse model was established by intratracheal instillation of 50 μL SiO₂ suspension (100 mg·mL⁻¹). The treatment models were prepared by intraperitoneal injection of 100 μL oxamate (225 mmol·L⁻¹ and 1125 mmol·L⁻¹). In the second part, induction of MLE-12 mouse alveolar type II epithelial cells was conducted with SiO₂. The in vitro experimental groups were ① SiO₂ induction groups: control group, 50 μg·mL⁻¹ SiO₂ group, 100 μg·mL⁻¹ SiO₂ group, and 200 μg·mL⁻¹ SiO₂ group, and ② oxamate treatment groups: control group, SiO₂ group (100 μg·mL⁻¹), low-dose oxamate (25 mmol·L⁻¹) treatment group, and high-dose oxamate (50 mmol·L⁻¹) treatment group. Pathological morphology of lung tissues was evaluated after hematoxylin-eosin (HE) staining; deposition of collagen in lung tissues was evaluated after sirius red staining; positive co-expression of prosurfactant protein C (Pro-SPC) and β-galactosidase was detected by immunofluorescence staining; positive expression of β-galactosidase in MLE-12 cells was detected by immunofluorescence staining. The protein expression levels of collagen type I (CoL I), fibronectin1 (FN1), hexokinase 2 (HK2), pyruvate kinase isozyme type M2 (PKM2), lactate dehydrogenase A (LDHA), p-ataxia telangiectasia and Rad3-related kinase (ATR), and cyclin-dependent kinase inhibitors p21, and p16 were detected by Western blotting. Results Compared with the control group, the protein expression levels of HK2, PKM2, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group and the SiO₂-induced MLE-12 cells (P＜0.05). The in vivo studies showed that, compared with the control group, the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the protein expression levels of CoL I, FN1, LDHA, p-ATR, p21, and p16 were significantly upregulated in the silicosis model group (P＜0.05). Compared with the silicosis model group, the oxamate treatment groups showed significant downregulation of the silicon nodule area, the collagen deposition area, the proportion of β-galactosidase positive cells, and the the CoL I, FN1, LDHA, p-ATR, p21, and p16 protein expression levels, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). The in vitro studies showed that, compared with the control group, the proportion of β-galactosidase positive cells and the protein expression levels of p-ATR, p21, and p16 were significantly upregulated in the SiO₂-induced group (P＜0.05). Compared with the SiO₂ group, the proportion of β-galactosidase positive cells and the LDHA, p-ATR, p21 and p16 protein expression levels were significantly downregulated in the oxamate treatment groups, and the high-dose oxamate treatment group showed a higher efficacy on these indicators than the low-dose oxamate treatment group (P＜0.05). Conclusion Lactate dehydrogenase inhibitor oxamate can alleviate silicotic fibrosis in mice by inhibiting the senescence of alveolar type II epithelial cells.

Objective To investigate the effects and mechanisms of icariin on changes in fear memory in post-traumatic stress disorder(PTSD)rats.Methods Thirty male SD rats were used to construct a rat model of single prolonged stress(SPS).The model rats were randomly divided into the SPS,icariin,and icariin + K252a(tyrosine kinase receptor B inhibitor)groups(n= 10 each;another 10 normal rats were used as the control group).The icariin and icariin + K252a groups were administered 20 mg/kg icariin by gavage once per day after SPS,while the control and SPS groups were administered the same dose of normal saline.K252a cells were injected into the lateral ventricles.After 2 weeks,anxiety,depression,and fear memory disorder in rats in each group were detected by the mine experiment,ele-vated cross maze experiment,and conditional fear test.The binding activity of icariin to brain-derived neurotrophic factor(BDNF)and the BDNF and TrkB expressions in the rat amygdala were detected by immunohistochemistry.The relative expressions of BDNF and TrkB pro-teins were detected by Western blotting.The expressions of postsynaptic density protein 95(PSD95)and synaptophysin(SYN)in the rat amygdala were detected using immunofluorescence.Results Icariin showed strong binding to BDNF.Compared with the control group,the times of entering the central area and the percentage of movement distance in the central area in the SPS group and the icariin+K252a group were significantly reduced.The open arm entry(OE)and arm opening time(OT)were significantly reduced,the freezing time and defecation times were significantly increased,and the expressions of the BDNF,TrkB,PSD95,and SYN proteins were significantly reduced(P<0.05).Compared with the SPS group,the icariin group rats had significantly increased times of entering the central area and percentages of movement distance in the central area,significantly increased OE and OT,significantly reduced the time of immobilization and defecation,and significantly increased the expressions of BDNF,TrkB,PSD95,and SYN proteins(P<0.05).Conclusion Icariin effectively alleviated the fear memory impairment induced by SPS in rats.This protective effect is related to BDNF/TrkB signaling pathway activation and upregulated PSD95 and SYN expression.

Objective To investigate the changes of serum metabolites in patients with occupational chronic lead poisoning using non-targeted metabolomics, and to screen differential metabolic pathways. Methods A total of 14 patients with occupational chronic lead poisoning were selected as the poisoning group, and 14 healthy people without occupational hazard exposure history were selected as the control group using the judgment sampling method. Serum of the individuals from the two groups was collected. Non-targeted metabolomics technology based on ultra high performance liquid chromatography-tandem mass spectrometry was used to detect serum metabolite levels in the two groups. Differential metabolites (DMs) were screened by the principal component analysis, partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis, and related metabolic pathways were explored. Results The blood lead level in the poisoning group was higher than that in the control group (median: 359.59 vs 5.04 μg/L, P<0.01). There were significant differences in serum metabolites between the poisoning group and control group. After the combination of results from the positive and negative ion patterns, a total of 89 DMs were screened in serum of patients in the poisoning group, including 50 upregulated and 39 downregulated metabolites compared with the control group. The serum DMs of poisoning group were mainly enriched in arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism in malignant tumor, glycerophospholipid metabolism and ether lipid metabolism compared with the control group (all P<0.05). Conclusion Abnormal changes of serum metabolic profile occurred in patients with occupational chronic lead poisoning. The metabolic pathways such as arginine biosynthesis, ABC transporter, purine metabolism, choline metabolism, glycerophospholipid metabolism and ether lipid metabolism may be involved in the occurrence and development of lead poisoning.

Objective To compare the blood glucose control effect and safety between insulin degludec and insulin aspart and insulin aspart 30 in non-obese patients with type 2 diabetes mellitus(T2DM).Methods Non-obese patients with T2DM were divided into treatment group and control group according to different treatment methods.The control group was treated with insulin aspart 30,and the treatment group was treated with insulin degludec and insulin aspart.Pancreatic islet related indicators[fasting C-peptide(FCP)and 2-hour postprandial C-peptide(2 h CP)],blood glucose control effect[fasting blood glucose(FBG),2-hour postprandial blood glucose(2 h PG)and glycated hemoglobin(HbA1c)],serum 25-hydroxyvitamin D[25(OH)D]and the risk of hypoglycemia were compared between the two groups.Results There were 41 cases in treatment group and 39 cases in control group.After treatment,FCP levels in treatment group and control group were(0.84±0.09)and(1.07±0.14)nmol·L-1;2 h CP levels were(1.03±0.15)and(1.69±0.17)nmol·L-1;FBG levels were(5.46±0.57)and(6.18±0.67)mmol·L-1;2 h PG levels were(8.17±0.85)and(9.03±0.94)mmol·L-1;HbA1 c were(5.35±0.57)％and(6.47±0.68)％;25(OH)D levels were(26.33±2.75)and(20.54±2.17)nmol·L-1,all with significant difference(all P＜0.05).The incidence rates of non-severe hypoglycemia in treatment group and control group were 14.63％and 35.90％,with statistically significant difference(P＜0.05).The incidence rates of severe hypoglycemia in treatment group and control group were 9.76％and 12.82％;the incidence rates of nocturnal hypoglycemia were 19.51％and 17.95％,without statistically significant difference(all P＞0.05).Conclusion The overall therapeutic effect of insulin degludec and insulin aspart on non-obese patients with T2DM is better than that of insulin aspart 30.The former can effectively regulate blood glucose and pancreatic islet cell function,lower the risk of non-severe hypoglycemia.