1.Establishment and evaluation of pendulum-like modified rat abdominal heart heterotopic transplantation model
Hongtao TANG ; Caihan LI ; Xiangyun ZHENG ; Senlin HOU ; Weiyang CHEN ; Zengwei YU ; Yabo WANG ; Dong TIAN ; Qi AN
Organ Transplantation 2025;16(2):280-287
Objective To introduce the modeling method of pendulum-like modified rat abdominal heart heterotopic transplantation model and evaluate the quality of the model. Methods An operator without transplantation experience performed 15 consecutive models, recorded the time of each step, changes in body weight and modified Stanford scores, and calculated the surgical success rate, postoperative 1-week survival rate and technical success rate. Ultrasound examinations was performed in 1 week postoperatively. Results The times for donor heart acquisition, donor heart processing, recipient preparation and transplantation anastomosis were (14.3±1.4) min, (3.5±0.6) min, (13.6±2.1) min and (38.3±5.2) min respectively. The surgical success rate was 87% (13/15), and the survival rate 1 week after operative was 100% (13/13). The improved Stanford score indicated a technical success rate of 92% (12/13), and the postoperative 1-week ultrasound examination showed that grafts with Stanford scores ≥3 had detectable pulsation and blood flow signals. Conclusions The pendulum-like modified rat abdominal heart heterotopic transplantation improved model further optimizes the operational steps with a high success rate and stable quality, may be chosen as a modeling option for basic research in heart transplantation in the future.
2.Degradation dynamics and residue determination of pyriclobenzuron in rice and paddy environments
Huanqi WU ; Junmin WANG ; Kongtan YANG ; Xumi WANG ; Nan FANG ; Liping DUAN ; Changpeng ZHANG ; Xiangyun WANG
Chinese Journal of Schistosomiasis Control 2025;37(2):201-208
Objective To establish a method for determination of pyriclobenzuron (PBU) residues in rice and paddy environments, and to determine the residual amounts and observe the degradation dynamics of PBU. Methods In July 2022, the paddies of Zhejiang Academy of Agricultural Sciences were selected as experimental fields, and were divided into the blank control group (no pesticide application), the 1-fold-concentration pesticide group (1 kg/667 m2), and the 5-fold-concentration pesticide group (5 kg/667 m2), with a 100 m2 area in each group. At the early tillering stage of rice, 20% suspension of PBU sulfate was sprayed once in the 1-fold-concentration and 5-fold-concentration pesticide groups, and rice plants, paddy water and soil samples were collected 2 h, and 1, 2, 3, 5, 7, 11, 14, 21, 28, 35, 49 d and 63 d following spraying PBU, while rice straw, field soil, brown rice and rice husk samples were collected 98 d following spraying. PBU was extracted and purified in samples using a quick, easy, cheap, effective, rugged, and safe (QuEChERS) pretreatment technique, and the PBU contents were determined in samples using ultrahigh performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The solvent standard working solution and matrix standard working solution were prepared. A linear regression equation was fitted between PBU concentration (x-axis) and peak area (y-axis), and the ratio of the slope (k) of the matrix standard curve to the slope (K) of the solvent standard curve was calculated to evaluate the matrix effect of PBU in samples. According to the Guidelines for Pesticide Residue Testing in Crops (NY/T 788—2018), the addition levels of PBU were set at 0.005, 0.050, 5.000, 1 000.000 mg/kg in rice plants, 0.005, 0.050, 2.000, 10.000 mg/kg in paddy water, 0.005, 0.050, 2.000 mg/kg in soil, and 0.005, 0.050, 5.000 mg/kg in brown rice and rice husks. The recovery and relative standard deviation (RSD) of PBU addition were calculated to evaluate the effectiveness of UPLC-MS/MS for determination of PBU contents. The first-order kinetic equation of PBU concentration was fitted in samples at different sampling time points to analyze the trends in PBU degradation in rice plants, paddy water, and soil, and the half-life of PBU was calculated in different samples. Results There was a good linear relationship between the mass concentration and peak area of PBU at concentrations of 0.000 1 to 0.020 0 mg/kg under solvent and matrix conditions (R2 = 0.985 8 to 0.999 7, t = -0.47 to 1.62, all P values < 0.01). The matrix effects of PBU were 70.26%, 65.42% and 65.12% in rice plants, brown rice and rice husks, indicating a matrix-inhibitory effect, and the matrix effect was 87.06% in soils, indicating a weak matrix effect. The recovery of PBU addition was 77.61% to 100.12% in different samples, with RSD of 1.43% to 6.74%, and a limit of quantification (LOQ) of 0.005 mg/kg, and the addition recovery and RSD met the requirements of the Guidelines for Pesticide Residue Testing in Crops (NY/T 788—2018), validating the effectiveness of UPLC-MS/MS assay. Following spraying PBU at a dose of 1 kg/667 m2, the half-life of PBU was 6.24 d in rice plants and 3.43 d in paddy water samples, respectively. The final residues of PBU were lower than the LOQ of 0.005 mg/kg in brown rice and rice husk samples 98 d following spraying PBU. Following spraying PBU at a dose of 5 kg/667 m2, the half-life of PBU was 15.75 d in rice plants and 7.62 d in paddy water samples, respectively. The final residue of PBU was lower than the LOQ of 0.005 mg/kg in brown rice 98 d following spraying PBU, and the final residue of PBU was 0.049 mg/kg in rice husks. Conclusions A simple, and highly accurate and precise UPLC-MS/MS assay has been developed for determination of PBU residues in rice plants and paddy environments through extraction and purification of PBU from matrix samples using QuEChERS pretreatment. After spraying PBU in paddies, the concentration of PBU gradually decreases in rice plants and paddy water over time, and the final residual concentration is low.
3.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
4.Renshentang Alleviates Atherosclerosis in Mice by Targeting TRPV1 to Regulate Foam Cell Cholesterol Metabolism
Yulu YUAN ; Ce CHU ; Xuguang TAO ; Zhen YANG ; Xiangyun CHEN ; Zhanzhan HE ; Yongqi XU ; Yuxin ZHANG ; Peizhang ZHAO ; Wanping CHEN ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):11-19
ObjectiveTo explore the effects of Renshentang on atherosclerosis (AS) in mice based on the role of transient receptor potential vanilloid1 (TRPV1) in regulating cholesterol metabolism in foam cells. MethodsNine SPF-grade 8-week-old C57BL/6J mice were set as a normal group, and 60 ApoE-/- mice were randomized into model, positive drug (simvastatin, 0.02 g·kg-1·d-1), and low-, medium-, and high-dose (1.77, 3.54, 7.08 g·kg-1·d-1, respectively) Renshentang groups (n=12) according to body weight. The normal group was fed with a normal diet, and the other groups were fed with a high-fat diet and given corresponding drugs by oral gavage for the modeling of AS. The mice were administrated with corresponding drugs once a day for 12 weeks. After the last administration and fasting for 12 h, the aorta was collected. Plaque conditions, pathological changes, levels of total cholesterol (TC), triglcerides (TG), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C), and the expression of TRPV1, liver X receptor (LXR), inducible degrader of the low-density lipoprotein receptor (IDOL), and low-density lipoprotein receptor (LDLR) in the aortic tissue were observed and detected by gross oil red O staining, HE staining, Western blot, immunohistochemistry, and real-time PCR. ResultsCompared with the normal group, the model group presented obvious plaque deposition in the aorta, raised levels of TC, TG, and LDL-C in the serum (P<0.01), up-regulated expression level of LDLR in the aorta (P<0.01), lowered level of HDL-C in the serum, and down-regulated expression levels of TRPV1, LXR, and IDOL in the aorta (P<0.05, P<0.01). Compared with the model group, the positive drug and Renshentang at different doses alleviated AS, elevated the levels of HDL-C, TRPV1, LXR, and IDOL (P<0.05, P<0.01), while lowering the levels of TC, TG, LDL-C, and LDLR (P<0.05, P<0.01). ConclusionRenshentang has a lipid-lowering effect on AS mice. It can effectively reduce lipid deposition, lipid levels, and plaque area of AS mice by activating TRPV1 expression and regulating the LXR/IDOL/LDLR pathway.
5.Rare giant solitary vagus neurofibroma of the neck: a case report and literature review.
Liaoliang HAO ; Xiangxiang WANG ; Jingxuan SHI ; Lu WANG ; Tianfeng DANG ; Xiangyun QIAO ; Qianqian ZHAO ; Leping LIANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2025;39(12):1192-1196
Neurofibromas are benign peripheral nerve sheath tumors. It is more common in neurofibromatosis type Ⅰ. However, isolated vagal nerve neurofibroma(VNN) of the neck is extremely rare, and only a few case reports have been reported. Its etiology and pathogenesis are not clear. The diagnosis is mainly based on pathological examination and immunohistochemistry, and surgical resection is the main treatment. This study reports a rare case of giant solitary vagus neurofibroma in the neck. The patient was a 29-year-old female who was found to have a mass on the right side of the neck by physical examination, which was considered to be a vagus nerve tumor by neck ultrasound and imaging examination. The tumor was completely removed during the operation, with the size of about 10.0 cm×2.5 cm, and the patient had no special discomfort. Postoperative pathology and immunohistochemistry confirmed neurofibroma. After surgery, the patient had right vocal cord paralysis, hoarseness, choking and paroxysmal cough. After swallowing function training and voice rehabilitation treatment in the department, the patient recovered satisfactorily. There was no complication and recurrence during the follow-up of 1 year. This article reviews the literature to improve the diagnosis and treatment of solitary vagus neurofibroma in the neck by combining its medical history, imaging features, pathology and immunohistochemistry, and surgical treatment.
Humans
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Female
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Adult
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Neurofibroma
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Vagus Nerve/pathology*
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Neck
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Cranial Nerve Neoplasms
6.Effects of infusion of irritant drugs on patients with midline catheter
Wenting XU ; Chang LIU ; Xiangyun LI ; Jie WANG ; Xiuzhu CAO ; Linfang ZHAO
Chinese Journal of Practical Nursing 2024;40(30):2351-2357
Objective:To explore the effects of infusion of irritant medications on the patients with midline catheter based on propensity score matching method and provide reference for medications infusion through midline catheter.Methods:Through a retrospective cohort study, the clinical data of 1 539 patients with midline catheter placement in Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from March 2019 to October 2022 were retrospectively analyzed, and the patients were divided into irritant medications group ( n=1 120) and non-irritant medications group ( n=419) according to the characteristics of the medications they were infused with, and then compared the patients of the two groups with midline catheter-related complications and catheter indwelling time based on the propensity score matching. Results:Among 1 539 patients, there were 656 males and 883 females, aged 18-92 (59.30 ± 18.76) years old. Before propensity score matching, there were statistically significant differences in age: (58.09 ± 18.72) years old, (62.55 ± 18.50) years old; hypertension:496 cases, 210 cases; diabetes:266 cases, 129 cases; white blood cell count:7.50(5.50, 9.70) × 10 9/L, 7.00(5.10, 9.50) × 10 9/L between the irritant medications group and non-irritant medications group ( t=4.18, χ2=4.18, 7.92, Z=-1.98, all P<0.05). After propensity score matching, there were 412 patients in the irritant medications group and 412 patients in the non-irritant medications group, and there was no significant difference in the general data between the two groups (all P>0.05). After propensity score matching, the rates of oozing, bleeding, catheter occlusion, catheter-related thrombosis, catheter dislodgement and total catheter complications between the two groups showed no statistically significant difference (all P>0.05). The catheter indwelling time in the irritant medications group was 10.00 (5.25, 16.75) days, which was longer than that in the non-irritant medications group for 6.00 (4.00, 11.00) days, the difference was statistically significant ( Z=-7.25, P<0.05). Conclusions:Infusion of irritant medications has no effect on the outcome of midline catheter, but monitoring and catheter maintenance should be strengthened in order to reduce the occurrence of cutheter related complications.
7.Burn-blast combined injury and important organ injury in rats induced by explosion in closed pipe:an observation study
Changmei WENG ; Guangming YANG ; Shuangbo ZHANG ; Yingguo ZHU ; Xiangyun CHENG ; Zhaoxia DUAN ; Jianyi KANG ; Jianmin WANG
Journal of Army Medical University 2024;46(12):1323-1335
Objective To establish a model of combined injury of thermal radiation and blast wave of gas explosion in closed pipeline,and investigate the characteristics of important organ injury induced by burn-blast combined injury in rats.Methods A total of 72 male SD rats(aged 8~10 weeks,weighing 200~10 g)were randomly divided into control group and mild and severe injured groups.After the model rats were inflicted with blast wave and thermal radiation,their physical parameters were detected and measured.The respiratory function of the survival rats was tested.In 24 h later,arterial blood gas analysis,blood biochemical tests,and detection for serum inflammatory factors and lung injury related protein levels were performed,and the pathological changes in the lung tissue and trachea were observed.Results The peak range of explosive blast wave overpressure was 209~493 kPa,and the temperature was 152~258 ℃.The mortality rate was 8.3%in the mild group and 53.1%in the severe group.Compared with the control group,longer inspiratory time(Ti)and relaxation time(Tr)and larger tidal volume(TV)(P<0.05),while lower respiratory frequency(f)were observed in the 2 injured groups within 6 h after injury(P<0.05).At 24 h after injury,the values of partial pressure of carbon dioxide(PaCO2),residual base value(BE)and bicarbonate(HCO3-)were increased significantly(P<0.05),while partial pressure of oxygen(PaO2)was decreased(P<0.05).The serum levels of alanine transaminase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP),total bilirubin(TBI)and total bile acid(TBA)were notably elevated(P<0.05).So were the levels of IL-1 β,TNF-α and IL-6(P<0.01).Various severities of hyperemia foci and inflammation in the tracheal mucosa were observed in the injured rats.The incidence of lung injury was high,and the pathological manifestations were dot-shaped hemorrhage to diffuse hemorrhage of the whole lobe,rupture of alveolar septum,thickening of septum,and infiltration of red blood cells and inflammatory cells.The levels of serum lung injury-related proteins were significantly increased(P<0.05).Conclusion A rat model which can highly simulate mild to severe burn-blast combined injury is constructed,which can meet the needs for rat model in study of explosive burn-blast compound injury.The main characteristics of the injury are lung injury,respiratory dysfunction,liver damage and secondary infection.
8.Study on the mechanism of Bushen Tongluo Prescription on mechanical injury of rat endometrium
Nian HUANG ; Xiaoou XUE ; Wei XIE ; Qing TONG ; Qian CHEN ; Xiangyun WANG
International Journal of Traditional Chinese Medicine 2024;46(10):1316-1322
Objective:To explore the effects and mechanism of Bushen Tongluo Prescription in mechanical injury of rat endometrium.Method:A total of 60 female SD rats were divided into the blank group, model group, estradiol valerate group, and Bushen Tongluo Prescription group according to the random number table method, with 15 rats in each group. Except for the blank group, the other three groups were used to establish a rat model of endometrial injury using mechanical injury method. After modeling, Bushen Tongluo Prescription group was orally administered with Bushen Tongluo Prescription decoction at a dosage of 2.1 g/kg, the estradiol group was orally administered with estradiol valerate at a dosage of 0.4 mg/kg, and the blank group and model group were orally administered with 0.5% CMC at an equal dosage, once a day, for a total of 8 days. Samples were taken on the 1st, 4th, and 8th day after gastric lavage. The thickness of the endometrium and glands were observed using HE staining, the degree of uterine tissue fibrosis was observed using Masson staining, and VEGF and TGF-β protein and mRNA expressions in uterine tissue were detected using Western blot and fluorescence quantitative PCR.Results:Compared with the Bushen Tongluo Prescription on the first day, the thickness of the endometrium and the number of glands increased on the eighth day ( P<0.05); compared with the model group, the number of glands in the Bushen Tongluo Prescription group increased on the 4th day of administration ( P<0.05), while the fibrotic area of the endometrium decreased on the 8th day of administration ( P<0.05); compared with the model group, on the 8th day of administration, the expression of VEGF protein and TGF-β1 in the Bushen Tongluo Prescription group increased ( P<0.05), and protein expression decreased ( P<0.05); compared with the model group, the group treated with Bushen Tongluo Prescription had TGFβ1 mRNA level on the first day increased ( P<0.05), while the level of TGF-β1mRNA decreased on the 8th day ( P<0.05). Conclusion:Bushen Tongluo Prescription can increase endometrial thickness and receptivity, effectively improve damaged endometrium, anti fibrotic and prevent endometrial adhesion by up-regulating VEGF protein expression and down-regulating TGF-β1 protein and mRNA expression.
9.Mechanism of Zhishi Xiebai Guizhitang in Treating AS Based on Regulation of Cholesterol Metabolism in Foam Cells by TRPA1
Zhanzhan HE ; Zhen YANG ; Xuguang TAO ; Xiangyun CHEN ; Wei DING ; Ce CHU ; Yulu YUAN ; Yuxin ZHANG ; Yongqi XU ; Peizhang ZHAO ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(10):1-10
ObjectiveTo explore the effect and mechanism of Zhishi Xiebai Guizhitang on the progression of atherosclerosis (AS) mice based on the regulation of cholesterol metabolism in foam cells by transient receptor potential channel ankyrin 1 (TRPA1). MethodThe AS model was established on apolipoprotein E knockout (ApoE-/-) mice with a high-fat diet. The mice were randomly divided into low-dose, middle-dose, and high-dose groups of Zhishi Xiebai Guizhitang (2.97, 5.94, 11.88 g·kg-1) and simvastatin group (0.002 g·kg-1), and the drug was administered along with a high-fat diet. C57BL/6J mice were fed an ordinary diet as a normal group. After the above process, the aorta and serum of mice were taken. The pathological changes of the aortic root were observed by hematoxylin-eosin (HE) staining. The lipid plaques in the aorta were observed by gross oil redness. Serum levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) were detected, and the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). Western blot and immunohistochemical method were used to analyze the expression of TRPA1, ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and mannose receptor (CD206). ResultFrom the perspective of drug efficacy, compared with the normal group, pathological changes such as plaque, a large number of foam cells, and cholesterol crystals appeared in the aorta of the model group, and the serum levels of TC, LDL-C, IL-1β, and IL-18 were significantly increased (P<0.01). The HDL-C level was significantly decreased (P<0.01), and the CD206 level in aortic tissue was significantly decreased (P<0.01). Compared with the model group, the lipid deposition in the aorta was alleviated in all drug administration groups. In addition, except for the high-dose group of Zhishi Xiebai Guizhitang, all drug administration groups could significantly decrease the levels of TC and LDL-C (P<0.01). In terms of inflammation, except for the middle-dose group of Zhishi Xiebai Guizhitang, the levels of IL-1β and IL-18 were significantly decreased in all drug administration groups (P<0.05). Moreover, Zhishi Xiebai Guizhitang could also up-regulate the levels of CD206, and the difference was significant in the middle-dose and high-dose groups (P<0.05). From the perspective of mechanism, the expression levels of TRPA1, ABCA1, and ABCG1 in the aorta in the model group were lower than those in the normal group (P<0.05). Compared with the model group, all drug administration groups significantly increased the expression of TRPA1 in the aorta (P<0.05), and the expressions of ABCA1 and ABCG1 were increased. The differences in the middle-dose and high-dose groups and the simvastatin group were significant (P<0.05), which was basically consistent with the trend of immunohistochemical results. ConclusionZhishi Xiebai Guizhitang can effectively reduce blood lipid and inflammation levels and inhibit the formation of aortic plaque. The mechanism may be explained as follows: the expressions of ABCA1 and ABCG1 downstream are increased through TRPA1, which promotes cholesterol outflow in foam cells, thereby regulating cholesterol metabolism, intervening in inflammation level to a certain extent, and finally treating AS.
10.Effect and Mechanism of Chinese Medicine in Treatment of Osteoporosis
Yulu YUAN ; Zhen YANG ; Wei DING ; Ce CHU ; Xuguang TAO ; Xiangyun CHEN ; Zhanzhan HE ; Peizhang ZHAO ; Yongqi XU ; Yuxin ZHANG ; Hongxia ZHAO ; Wenlai WANG
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(4):290-298
Osteoporosis (OP) is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation, which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity, reduce the calcium supply to the bone, and lower the calcium content in the bone, thus triggering OP. Drugs are the main anti-OP therapy in modern medicine, which, however, may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP, being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency, regulate bone cell and calcium metabolism, which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 (TRPV5 and TRPV6, respectively) affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine (TRPV6) and kidney (TRPV5). Therefore, TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines, which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades, especially the mechanism of regulating calcium metabolism, aiming to provide new ideas for the basic research, clinical application, and drug development of OP treatment.

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