BACKGROUND:The guinea pig is considered to be the most useful spontaneous model for evaluating primary osteoarthritis in humans because of its similar knee joint structure and close histopathologic features to those of humans. OBJECTIVE:To investigate the pathological process of spontaneous knee osteoarthritis in guinea pigs by analyzing the histopathology of the total knee joint of guinea pigs aged 1 to 18 months. METHODS:Eight healthy female Hartley guinea pigs in each age group of 1,6,10,14,16,and 18 months old were selected.The quadriceps femoris was taken for hematoxylin-eosin staining,and the total knee joint was stained with hematoxylin-eosin and toluidine blue.The histopathology of the cartilage,subchondral bone,synovium,meniscus,and muscles were observed under light microscope.Mankin's score and synovitis score were compared,and the correlation analysis was conducted. RESULTS AND CONCLUSION:As the guinea pig age increased,the Mankin's score increased(P<0.05),and the pathological score of synovitis also gradually increased(P<0.05),and there was a significant positive correlation between the two(r=0.641,P<0.001).The incidence rate of subchondral bone marrow lesion in 18-month-old guinea pigs was 50%,and the incidence of meniscus injury was 37.5%.In addition,osteophyte and narrowing of the joint space were observed,and only a few guinea pigs had inflammation in the quadriceps femoris.To conclude,guinea pigs develop significant cartilage defects,synovial inflammation,subchondral bone lesions,meniscus injury,osteophyte formation,and joint space narrowing as they age,all of which are similar to the pathological processes of primary knee osteoarthritis in humans,making it an ideal model of spontaneous knee osteoarthritis.

BACKGROUND: Prospective evidence on how offspring number influences morbidity and mortality remains limited. This study investigated the associations between number of offspring and morbidity and mortality risks among 0.5 million Chinese adults. METHODS: By using data from the China Kadoorie Biobank (CKB; n = 512,723, an approximately 12-year follow-up), sex-stratified phenome-wide association study (PheWAS) analyses were conducted to investigate associations between offspring number (without vs . with offspring; more than one vs . one offspring) and risks of ICD10-coded morbidity and mortality. Sex-specific adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) were estimated by Cox proportional-hazards models. RESULTS: Among 210,129 men and 302,284 women aged 30-79 years, 1,338,837 incident events were recorded. PheWAS results revealed that offspring number was associated with disease risks across multiple systems. Cox models showed that childless men ( vs . one offspring) had higher risks for nine of 36 diseases, while childless women for five of 37. Each additional offspring was associated with reduced risks of mental and behavioral disorders in men (aHR [95% CI] = 0.93 [0.87-0.98]) and both mental and behavioral disorders (aHR [95% CI] = 0.93 [0.89-0.97]) and breast cancer (aHR [95% CI] = 0.82 [0.78-0.86]) in women. However, each additional offspring was associated with a 4% increase in the risk of cholelithiasis and cholecystitis in women (aHR [95% CI] = 1.04 [1.02-1.07]). Among 282,630 patients, 44,533 deaths were documented. Childless patients had higher mortality risk in both men (aHR [95% CI] = 1.37 [1.28-1.47]) and women (aHR [95% CI] = 1.27 [1.15-1.41]). For men, each additional offspring reduced mortality by 4% (aHR [95% CI] = 0.96 [0.95-0.98]), while for women, the lowest risk was observed among those with three to four offspring ( Pnonlinear <0.0001). CONCLUSIONS Offspring number is closely linked to morbidity and mortality risks. Further research is warranted to verify our findings and clarify the underlying mechanisms involved.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; China/epidemiology* ; Morbidity ; Proportional Hazards Models ; Prospective Studies ; Risk Factors ; Family Characteristics ; Mortality ; East Asian People

The antidepressant activity and molecular mechanisms of Yueju Wan volatile oil were investigated. The Yueju Wan volatile oil was extracted by using supercritical CO_2. Gas chromatography-mass spectrometry(GC-MS) combined with network pharmacology identified 28 chemical constituents in Yueju Wan volatile oil, primarily terpenes and lactones. A total of 123 overlapping targets were associated with depression, including core targets of interleukin-1β(IL-1β), signal transducer and activator of transcription 3(STAT3), and caspase-3(CASP3). These targets were mainly involved in the prolactin, advanced glycation end products/receptor(AGE/RAGE), and phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) signaling pathways. A reserpine-induced depression mouse model was established to evaluate the therapeutic effects and mechanisms of Yueju Wan volatile oil. The effects of Yueju Wan volatile oil on depression-like behavior in mice were evaluated by analyzing body mass, body temperature index, tail suspension immobility time, forced swimming immobility time, and sucrose preference. Hematoxylin-eosin(HE) staining revealed neuronal protection of Yueju Wan volatile oil in the brain of mice. Enzyme-linked immunosorbent assay(ELISA) and Western blot were employed to detect the protein expression of AGEs, IL-1β, phosphorylated PI3K(p-PI3K), Akt, phosphorylated Akt(p-Akt), nuclear factor κB(NF-κB), and brain-derived neurotrophic factor(BDNF). Behavioral evaluation showed that Yueju Wan volatile oil could effectively control the decline of body mass and body temperature of depressed mice, reduce tail suspension and swimming immobility time, and enhance their preference for sucrose. Histopathological examination showed that Yueju Wan volatile oil could alleviate the neuronal damage in CA1 and dentate gyrus(DG) of the hippocampus of mice. ELISA and Western blot results showed that Yueju Wan volatile oil could significantly increase the protein expression levels of PI3K, Akt, and BDNF and significantly decrease the protein expression levels of AGEs, IL-1β, p-PI3K, p-Akt, and NF-κB in the hippocampus of mice. Furthermore, the p-PI3K/PI3K and p-Akt/Akt ratios were significantly decreased at medium and high doses. These findings suggest that the aromatherapy of Yueju Wan volatile oil can significantly improve reserpine-induced depression-like behavior in mice, which may be related to reducing the expression of neuronal membrane protein AGEs, reducing the phosphorylation levels of PI3K and Akt, inhibiting NF-κB entry into the nucleus, and alleviating the release of pro-inflammatory factors and nerve injury.
Animals ; Antidepressive Agents/chemistry* ; Mice ; Proto-Oncogene Proteins c-akt/immunology* ; Phosphatidylinositol 3-Kinases/immunology* ; Oils, Volatile/chemistry* ; Male ; Drugs, Chinese Herbal/chemistry* ; Signal Transduction/drug effects* ; Depression/metabolism* ; Glycation End Products, Advanced/immunology* ; Humans

Fritillariae Cirrhosae Bulbus is the dried bulb of perennial herbaceous plants in the Fritillaria genus(Liliaceae family) and is a representative traditional Chinese medicinal material with distinctive regional characteristics. Clinically, it is widely used in the treatment of dry cough, bronchial asthma, and other respiratory diseases, possessing significant medicinal and economic value and being highly esteemed in TCM. Currently, Fritillariae Cirrhosae Bulbus primarily relies on wild harvesting. However, due to excessive collection, its wild resources have drastically declined, and all source species have been classified as category Ⅱ in the List of National Key Protected Wild Plants, exacerbating the supply-demand imbalance in the market. To mitigate this issue, large-scale cultivation through the domestication of wild Fritillariae Cirrhosae Bulbus has become an inevitable trend. However, its strict environmental requirements, low propagation efficiency, high seedling mortality, and immature cultivation techniques have severely hindered industrialization. This study investigates the domestication process of Fritillariae Cirrhosae Bulbus, focusing on seed propagation, seedling cultivation, and medicinal material production. It also reviews the species and distribution of wild resources, their endangered status, market supply-demand dynamics, and the historical and current development of domestication. The findings indicate that enhancing propagation efficiency, optimizing cultivation models, and distinguishing between seed propagation and medicinal material production are key measures to accelerate the industrialization of domesticated Fritillariae Cirrhosae Bulbus. This research aims to promote the industrialization of Fritillariae Cirrhosae Bulbus domestication and provide a reference model for the conservation and sustainable utilization of rare and endangered medicinal plant resources.
Fritillaria/chemistry* ; Endangered Species ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/economics* ; China

OBJECTIVE: To explore the displacement and pressure distribution of American Chiropractic in a model of third lumbar syndrome based on finite element analysis. METHODS: On March 2021, CT and MRI images of a 23-year-old male patient with right third lumbar syndrome were selected. A 3D stl model was established using Mimics and CATIA, and the data was imported into Hypermesh, Abaqus & ANSYS. The elastic modulus and Poisson's ratio of the affected side material were adjusted to establish its finite element model. Based on the comparison of the operating positions and routines of the American Chiropractic and the lumbar spine oblique pull method, but with differences in the focus and direction of force, the experimental group simulated the American Chiropractic with the healthy side (left side) lying position of the model. The upper endplate of L₃ and the lower part below L₃ twisted accordingly with the body position, we applied a vertical forward thrust of 246 N to the plane formed by the L₄, L₅ spinous processes and L₄ upper articular processes;The control group simulates the oblique pull method of the lumbar spine, requiring the model to lie on the healthy side (left side), fix the upper endplate of L₄, and perform a horizontal rotation along the longitudinal axis of L₃ vertebral body. At this time, the contact force in the upward direction is also set to 246 N. Compare the displacement and stress differences between the L₁-L₅ intervertebral bodies, intervertebral discs, articular processes, and transverse process muscles in two intervention models. RESULTS: ① Under safe load conditions, a test force of 246 N was applied to the model, and the maximum vertebral displacement occurred on the right side of the L₃ vertebral body (1.197 mm) after manual intervention in the control group. The vertebral displacement between L₁-L₅ induced by manual intervention in the experimental group was smaller than that of the control group's manual intervention (P<0.05). ② The maximum vertebral body stress occurred on the right side of the L₃ vertebral body after manual intervention in the control group (98.425 MPa). The stress on each vertebral body formed by the experimental group's manual intervention was lower than that of the control group's manual intervention (P<0.05). ③The maximum intervertebral disc stress occurred on the right side of the L_2,3 intervertebral disc (6.282 MPa) after manual intervention in the control group. ④ The maximum joint process stress occurred on the right side of the L₄ upper joint process after manual intervention in the experimental group (1.587 MPa). The joint process stress on the left side below L₁ and the left side above and below L₂ induced by manual intervention in the experimental group was lower than that of the control group (P<0.05). ⑤The maximum stress on the intertransverse process muscle was observed at the right lateral L₃ process end (31.960 MPa) of L_3,4 in the control group after manual intervention. The stress on the L_2,3 and L_4,5 segments of the intertransverse process muscle induced by manual intervention in the experimental group was lower than that of the control group's manual intervention (P<0.05). CONCLUSION The mechanical feedback of the L₁-L₅ vertebral body, the lower left side of the articular process L₁, the upper and lower left side of the articular process L₂, and the L_2,3 and L_4,5 segments of the transverse process muscle in the model indicates that performing American Chiropractic for the treatment of third lumbar transverse process syndrome can accurately hit the target pain point and allow the patient's tissue to form a low stress and low tension state after manual operation, thereby reducing the possibility of tissue damage caused by hypertonia after intervertebral joint movement, making it relatively safe. The application of American Chiropractic will be a new supplement to the traditional treatment plan for third lumbar transverse process syndrome.
Humans ; Finite Element Analysis ; Male ; Lumbar Vertebrae/physiopathology* ; Biomechanical Phenomena ; Young Adult ; Manipulation, Chiropractic ; Adult ; Tomography, X-Ray Computed ; Magnetic Resonance Imaging

Objective:To describe the distribution of lipoprotein (a) [Lp(a)] levels in non-arteriosclerotic cardiovascular disease (ASCVD) population in China and explore its influencing factors.Methods:This study was based on a nested case-control study in the CKB study measured plasma biomarkers. Lp(a) levels was measured using a polyclonal antibody-based turbidimetric assay certified by the reference laboratory and ≥75.0 nmol/L defined as high Lp(a). Multiple logistic regression model was used to examine the factors related to Lp(a) levels.Results:Among the 5 870 non-ASCVD population included in the analysis, Lp(a) levels showed a right-skewed distribution, with a M ( Q1, Q3) of 17.5 (8.8, 43.5) nmol/L. The multiple logistic regression analysis found that female was associated with high Lp(a) ( OR=1.23, 95% CI: 1.05-1.43). The risk of increased Lp(a) levels in subjects with abdominal obesity was significantly reduced ( OR=0.68, 95% CI: 0.52-0.89). As TC, LDL-C, apolipoprotein A1(Apo A1), and apolipoprotein B(Apo B) levels increased, the risk of high Lp(a) increased, with OR (95% CI) for each elevated group was 2.40 (1.76-3.24), 2.68 (1.36-4.93), 1.29 (1.03-1.61), and 1.65 (1.27-2.13), respectively. The risk of high Lp(a) was reduced in the HDL-C lowering group with an OR (95% CI) of 0.76 (0.61-0.94). In contrast, an increase in TG levels and the ratio of Apo A1/Apo B(Apo A1/B) was negatively correlated with the risk of high Lp(a), with OR (95% CI) of 0.73 (0.60-0.89) for elevated triglyceride group, and OR (95% CI) of 0.60 (0.50-0.72) for the Apo A1/B ratio increase group (linear trend test P≤0.001 except for Apo A1). However, no correlation was found between Lp(a) levels and lifestyle factors such as diet, smoking, and physical activity. Conclusions:Lp(a) levels were associated with sex and abdominal obesity, but less with lifestyle behaviors.

Objective:To investigate the effect of high-fat and low-carbohydrate diet combined with radiotherapy on the tumor microenvironment of mice with lung xenografts.Methods:C57BL/6J mice were selected to establish the Lewis lung cancer model, and they were divided into the normal diet group, the high-fat and low-carbohydrate diet group, the normal diet + radiotherapy group, and the high-fat and low-carbohydrate diet + radiotherapy group, with 18 mice in each group. The mice in the normal diet group and the normal diet + radiotherapy group were fed with the normal diet with 12.11% fat for energy supply, and the mice in the high-fat and low-carbohydrate diet group and the high-fat and low-carbohydrate diet + radiotherapy group were fed with high-fat and low-carbohydratediet with 45.00% fat for energy. On the 12th to 14th days, the tumor sites of the mice in the normal diet + radiotherapy group and the high-fat and low-carbohydrate diet + radiotherapy group were treated with radiotherapy, and the irradiation dose was 24 Gy/3f. The body weight, tumor volume, blood glucose and blood ketone level, liver and kidney function, and survival status of the mice were observed and monitored. Immunohistochemical staining was used to detect the tumor-associated microangiogenesis molecule (CD34) and lymphatic endothelial hyaluronan receptor 1 (LYVE-1), Sirius staining was used to detect collagen fibers, and multiplex immunofluorescence was used to detect CD8 and programmed death-1 (PD-1). Expression of immune cell phenotypes (CD3, CD4, CD8, and Treg) was detected by flow cytometry.Results:On the 27th day after inoculation, the body weigh of the common diet group was(24.78±2.22)g, which was significantly higher than that of the common diet + radiotherapy group [(22.15±0.48)g, P=0.030] and high-fat low-carbohydrate diet + radiotherapy group [(22.02±0.77)g, P=0.031)]. On the 15th day after inoculation, the tumor volume of the high-fat and low-carbohydrate diet + radiotherapy group was (220.88±130.05) mm 3, which was significantly smaller than that of the normal diet group [(504.37±328.48) mm 3, P=0.042)] and the high-fat, low-carbohydrate diet group [(534.26±230.42) mm 3, P=0.016], but there was no statistically significant difference compared with the normal diet + radiotherapy group [(274.64±160.97) mm 3]. In the 4th week, the blood glucose values of the mice in the high-fat and low-carbohydrate diet group were lower than those in the normal diet group, with the value being (8.00±0.36) mmol/L and (9.57±0.40) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). The blood ketone values of the mice in the high-fat and low-carbohydrate diet group were higher than those in the normal diet group, with the value being (1.00±0.20) mmol/L and (0.63±0.06) mmol/L, respectively, in the second week. In the third week, the blood ketone values of the two groups of mice were (0.90±0.17) mmol/L and (0.70±0.10) mmol/L, respectively, and the difference was statistically significant ( P＜0.05). On the 30th day after inoculation, there were no significant differences in aspartate aminotransferase, alanine aminotransferase, creatinine, and urea between the normal diet group and the high-fat, low-carbohydrate diet group (all P＞0.05). The hearts, livers, spleens, lungs, and kidneys of the mice in each group had no obvious toxic changes and tumor metastasis. In the high-fat and low-carbohydrate diet + radiotherapy group, the expression of CD8 was up-regulated in the tumor tissues of mice, and the expressions of PD-1, CD34, LYVE-1, and collagen fibers were down-regulated. The proportion of CD8 + T cells in the paratumoral lymph nodes of the high-fat and low-carbohydrate diet + radiotherapy group was (25.13±0.97)%, higher than that of the normal diet group [(20.60±2.23)%, P＜0.050] and the normal diet + radiotherapy group [(19.26±3.07)%, P＜0.05], but there was no statistically significant difference with the high-fat and low-carbohydrate diet group [(22.03±1.75)%, P＞0.05]. The proportion, of CD4 + T cells in the lymph nodes adjacent to the tumor in the normal diet + radiotherapy group (31.33±5.16)% and the high-fat and low-carbohydrate diet + radiotherapy group (30.63±1.70)% were higher than that in the normal diet group [(20.27±2.15)%, P＜0.05] and the high-fat and low-carbohydrate diet group (23.70±2.62, P＜0.05). Treg cells accounted for the highest (16.58±5.10)% of T cells in the para-tumor lymph nodes of the normal diet + radiotherapy group, but compared with the normal diet group, the high-fat and low-carbohydrate diet group, and the high-fat and low-carbohydrate diet + radiotherapy group, there was no statistically significant difference (all P＞0.05). Conclusion:High-fat and low-carbohydrate diet plus radiotherapy can enhance the recruitment and function of immune effector cells in the tumor microenvironment, inhibit tumor microangiogenesis, and thus inhibit tumor growth.

Trichinosis is a global food-borne zoonotic parasitic disease caused by Trichinella spiralis(T.spiralis),which causes serious harm to animal production,and the public health safety of humans and animals.T.spiralis has a complex devel-opment history,and its entire life cycle is completed in the same host.To coexist with the host,it has evolved various immune escape mechanisms for avoiding immune clearance by the host,thus establishing long-term chronic infection.In this study,to aid in understanding the pathogenic mechanism of T.spiralis,the immune escape mechanism of Trichinella is discussed from three aspects:the molecular role of antigens in various stages,the immune regulatory effect on the host,and the formation of cysts to generate immune isolation.

Objective:To compare the efficacy and clinical value of high-throughput sequencing(HTS)and Sanger sequencing in detecting ABL kinase domain mutations in patients with chronic myeloid leukemia(CML).Methods:A total of 198 samples of 147 CML patients from July 2017 to March 2021 in Henan Cancer Hospital were collected and underwent high-throughput sequencing and Sanger sequencing to detect the mutations in ABL kinase domain,and the relevant clinical data were collected for comparative analysis.Results:The proportion of total mutations and ≥ 2 mutations detected by high-throughput sequencing were significantly higher than those detected by Sanger sequencing(P=0.01;P=0.046).≥ 2 mutations were detected in 22 cases,of which 5 cases(22.7％)had compound mutations.High-throughput sequencing can detect low level mutations that cannot be detected by Sanger sequencing.In 198 samples,25(12.6％)were low level mutations,33(16.7％)were high level mutations and 10(5.1％)were mixed high and low level mutations.In the analysis of related clinical factors,the total mutation rate and the low level mutation rate in the optimal period,failure period and warning period were gradually increased(total mutation rate,P=0.016;low level mutation rate,P=0.005).The mutation rate of the samples with additional chromosomal abnormalities was also significantly increased(P=0.009).The mutation rate of patients who received first-and second-line treatment was significantly lower than that of patients who received third-or higher-line treatment(P=0.006).Analysis based on variant allele frequency(VAF)of the mutation site was helpful to visually evaluate the clonal evolution status of TKI-resistance CML cells.Conclusion:High-throughput sequencing is more sensitive and accurate than Sanger sequencing in mutation detection,which is helpful to accurately and visually evaluate TKI treatment response and optimize treatment strategy for CML.

Aim To investigate the mechanism of py-roptosis mediated by the NLRP3/caspase-1/GSDMD signaling pathway and the intervention effect of Radix Angelica Sinensis and Radix Astragalus ultrafiltration extract(RAS-RA)in radiation-induced pulmonary fi-brosis.Methods Fifty Wistar rats were randomly di-vided into five groups,with ten rats in each group.Ex-cept for the blank control group,all other groups of rats were anesthetized and received a single dose of 40 Gy X-ray local chest radiation to establish a radiation-in-duced pulmonary fibrosis rat model.After radiation,the rats in the RAS-RA intervention groups were orally administered doses of 0.12,0.24 and 0.48 g·kg-1 once a day for 30 days.The average weight and lung index of the rats were observed after 30 days of contin-uous administration.Hydroxyproline(HYP)content in lung tissue was determined by hydrolysis method.The levels of IL-18 and IL-1 β in serum were detected by ELISA.Lung tissue pathological changes were ob-served by HE and Masson staining.Ultrastructural changes in lung tissue were observed by transmission e-lectron microscopy.The expression levels of NLRP3/caspase-1/GSDMD pyroptosis pathway-related proteins and fibrosis-related proteins in lung tissue were detec-ted by Western blot.Results Compared with the blank group,the HYP content in lung tissue and the levels of IL-18 and IL-1 β in serum significantly in-creased in the model group(P＜0.01).HE and Mas-son staining showed inflammatory cell infiltration and collagen fiber deposition.Transmission electron mi-croscopy revealed increased damaged mitochondria,disordered arrangement,irregular morphology,shallow matrix,outer membrane rupture,mostly fractured and shortened cristae,mild expansion,increased electron density of individual mitochondrial matrix,mild sparse structure of lamellar bodies,partial disorder,unclear organelles,and characteristic changes of pyroptosis.Western blot analysis showed increased expression of caspase-1,GSDMD,NLRP3,CoL-Ⅰ,α-SMA,and CoL-Ⅲ proteins(P＜0.01).Compared with the model group,the RAS-RA intervention group showed signifi-cant improvement in body mass index and lung index of rats,decreased levels of IL-18 and IL-1 β inflammatory factors(P＜0.01),improved mitochondrial structure,reduced degree of fibrosis,and decreased expression of caspase-1,GSDMD,NLRP3,COL-Ⅰ,COL-Ⅲ,and α-SMA proteins in lung tissue(P＜0.01).Conclusion RAS-RA has an inhibitory effect on radiation-in-duced pulmonary fibrosis,and its mechanism may be related to the inhibition of pyroptosis through the regu-lation of the NLRP3/caspase-1/GSDMD signaling pathway.