1.Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction
LIU Mingyi ; MIAO Xiaoyu ; CAI Yunfan ; WANG Yan ; SUN Xiaotang ; KANG Jingrui ; ZHAO Yao ; NIU Lina
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):29-40
Objective:
To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.
Methods:
The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group
Results:
The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group.
Conclusion
The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.
2.Development of brush ionization probe mass spectrometry for convenient on-site detection of traditional Chinese medicine
Junxian WU ; Chaofa WEI ; Ceyu MIAO ; Jiaquan XU ; Xiang LI ; Li ZHOU ; Shuanglong WANG ; Liping KANG ; Zidong QIU
Science of Traditional Chinese Medicine 2026;4(1):81-86
Objective: To develop a convenient, direct, and highly sensitive method for screening trace chemical additives in complex Chinese patent medicines, thereby addressing core technological bottlenecks in pharmaceutical analysis and quality control. Methods: A brush ionization probe device was independently designed and constructed, and an efficient detection method was established through systematic optimization of key parameters. Twenty-three Chinese patent medicine samples, representing 6 dosage forms (capsules, tablets, pills, granules, powders, and liquid preparations), were analyzed using 10 common chemical additives as target analytes. Results: All samples were successfully analyzed without complex pretreatment, and 5 chemical additives were detected in 7 Chinese patent medicines. The brush ionization probe device exhibited cost-effectiveness (~0.2 USD per probe), operational simplicity, rapid analysis (~10s per sample), high efficiency, and minimal reagent consumption (~10 μL per sample). Conclusion: This advancement is expected to provide an innovative scientific tool for improving the generality and convenience of on-site quality control, while promoting technological progress in disciplines such as pharmacology and traditional Chinese medicine.
3.Risk factors for deep vein thrombosis before lower limb fracture surgery in middle-aged and elderly patients
Bin KANG ; Fenfang HONG ; Jintu CHENG ; Yabin CHEN ; Jie MIAO
International Journal of Laboratory Medicine 2025;46(19):2402-2407
Objective To study the risk factors of preoperative deep vein thrombosis(DVT)in middle-aged and elderly patients with lower limb fractures,and establish and evaluate the constructed nomogram model.Methods A retrospective analysis was conducted on the clinical data of totally 240 middle-aged and elderly patients with lower limb fractures at Quanzhou First Hospital Affiliated to Fujian Medical University from July 2023 to June 2024.According to whether the patient had DVT before surgery,they were divided into a DVT group of 75 cases and a non DVT group of 165 cases.The differences in clinical data and some labora-tory indicators levels at the time of initial admission,including platelets(PLT),prothrombin time(PT),ac-tive partial thromboplastin time(APTT),fibrinogen(FIB),thrombin time(TT),D-dimer(D-D),total pro-tein(TP),albumin(ALB),triglycerides(TG),cholesterol(CHOL),high-density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C)between two groups were compared.Logistic binary regression was used to analyze the risk factors of DVT and a nomogram model was constructed.Receiver oper-ating characteristic(ROC)curve was used to evaluate the diagnostic efficacy of various risk factors and nomo-gram model in screening DVT.Results Compared age and D-D levels of the DVT group were significantly higher(P<0.001),while the levels of APTT,TP and ALB were significantly lower(P<0.05),and the pro-portion of DVT combined with internal diseases and the proportion of fractures in the femur were significantly higher(P<0.001).The above-mentioned differential indicators were all single risk factors for DVT.ROC curve analysis showed that except for comorbidities of internal medicine,all other risk factors could effectively screen for DVT(P<0.05),the area under the curve(AUC)was 0.573-0.706,and the constructed nomo-gram model could effectively improve AUC to 0.797.Conclusion The nomogram model constructed based on single risk factors for DVT in this study is helpful for clinical assessment of the risk of DVT occurrence in pa-tients at the early stage of admission,intuitively and effectively.
4.Differences and Mechanisms of Combined Use of "Raw and Fried Ziziphi Spinosae Semen" in Anmeidan and Its Disassembled Prescriptions in Improving Anxiety and Cognitive Impairment in Insomnia Rat Model Based on Serum Metabolomics
Kang SUN ; Bo XU ; Zijing YE ; Miao ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):36-43
ObjectiveTo investigate the differences in efficacy and endogenous metabolic mechanisms of Anmeidan with combined use of raw and fried Ziziphi Spinosae Semen and its disassembled prescriptions in treating anxiety and cognitive impairment in insomnia rats. MethodsSixty rats were randomly divided into six groups (n=10 per group): blank group, model group, suvorexant group (30 mg·kg-1), Anmeidan group (9.09 g·kg-1), Anmeidan with absence of raw Ziziphi Spinosae Semen group (7.38 g·kg-1), and Anmeidan with absence of fried Ziziphi Spinosae Semen group (7.38 g·kg-1). An insomnia model was constructed by intraperitoneal injection of para-chlorophenylalanine (PCPA), followed by gavage administration of Anmeidan or its disassembled prescriptions. Anxiety levels were assessed using the open field test, while cognitive ability was evaluated via the novel object recognition test. The pathological morphology of hippocampal neurons was examined using electron microscopy. Serum samples were analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) for principal component analysis, metabolic profiling, identification of differential metabolites, and metabolic pathway analysis. ResultsCompared with the blank group, the model group exhibited significantly increased exercise mileage, exercise time, and the ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones exhibited a marked increase (P<0.05, P<0.01), while the novel object recognition index significantly decreased (P<0.05). Compared with the model group, the Anmeidan and suvorexant groups showed significantly reduced exercise mileage and exercise time (P<0.01). The ratio of the number of entries into the peripheral zone to the total number of entries into both the peripheral and central zones decreased (P<0.05), and a significant increase in the novel object recognition index (P<0.01). However, the disassembled prescription groups showed no significant improvement in open field test and novel object recognition test indices. Electron microscopy revealed that the Anmeidan group improved the pathological morphology of hippocampal neurons in insomnia rats. Metabolomics analysis identified 10 potential differential metabolites associated with Anmeidan's therapeutic effects, involving metabolic pathways related to phenylalanine and tryptophan biosynthesis and metabolism, as well as the serotonergic pathway. ConclusionThe combined use of raw and fried Ziziphi Spinosae Semen in Anmeidan is more effective than its disassembled prescriptions in alleviating anxiety and cognitive impairment in PCPA-induced insomnia rats. The underlying mechanism may be associated with metabolic pathways related to phenylalanine, tryptophan, and serotonin.
5.Theoretical Exploration of Same "Etiology-Mechanism-Syndrome-Treatment-Prevention" in Insomnia and Skin Aging
Bo XU ; Miao ZHU ; Kang SUN ; Yuan PENG ; Ping WANG ; Li YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(10):72-78
Sleep, skin, and health are closely interconnected. Clinically, insomnia has a high incidence and is often accompanied by or secondary to skin aging. The two conditions exhibit "different diseases with the same syndrome", significantly affecting the physical and mental health of the Chinese population. Preventing and treating skin aging by improving insomnia is an important strategy, with the principle of "treating different diseases with the same approach" serving as a crucial therapeutic guideline. However, effective clinical prevention and treatment methods for both conditions remain lacking. Traditional Chinese medicine (TCM) has a profound theoretical foundation and notable efficacy in the concurrent treatment of insomnia and skin aging, yet there are few reports on the etiology, pathogenesis, therapeutic principles, and treatment methods of their shared treatment, warranting further exploration. Based on holistic view and syndrome differentiation and treatment in TCM, this study systematically investigates the theoretical origins of the shared manifestations of insomnia and skin aging from multiple dimensions, including etiology, pathological location, pathogenesis, disease nature, and prevention and treatment strategies. As early as Huangdi's Internal Classic (Huangdi Neijing), it was recognized that mental clarity during the day, sound sleep at night, and firm, healthy skin are key indicators of external health, whereas daytime lethargy, poor sleep quality, and dry, withered skin are prominent signs of aging. Maintaining mental clarity during the day and restful sleep at night is essential for skin integrity and healthy aging. Later medical scholars proposed that the common etiology of insomnia and skin aging lies in "internal-external interactions", with the pathological location involving "the five organ systems". The primary pathogenesis includes "deficiency, fire, stagnation, phlegm, and blood stasis", while the disease nature is often characterized by "a combination of deficiency and excess". Treatment should be guided by syndrome differentiation, following the principle of balancing Yin and Yang. This theoretical exploration enriches and advances TCM understanding of disease onset and prevention, providing theoretical guidance for the clinical prevention and treatment of insomnia-associated skin aging and contributing to the realization of the "Healthy China" initiative.
6.Predicting Postoperative Circulatory Complications in Older Patients: A Machine Learning Approach.
Xiao Yun HU ; Wei Xuan SHENG ; Kang YU ; Jie Tai DUO ; Peng Fei LIU ; Ya Wei LI ; Dong Xin WANG ; Hui Hui MIAO
Biomedical and Environmental Sciences 2025;38(3):328-340
OBJECTIVE:
This study examines utilizes the advantages of machine learning algorithms to discern key determinants in prognosticate postoperative circulatory complications (PCCs) for older patients.
METHODS:
This secondary analysis of data from a randomized controlled trial involved 1,720 elderly participants in five tertiary hospitals in Beijing, China. Participants aged 60-90 years undergoing major non-cardiac surgery under general anesthesia. The primary outcome metric of the study was the occurrence of PCCs, according to the European Society of Cardiology and the European Society of Anaesthesiology diagnostic criteria. The analysis metrics contained 67 candidate variables, including baseline characteristics, laboratory tests, and scale assessments.
RESULTS:
Our feature selection process identified key variables that significantly impact patient outcomes, including the duration of ICU stay, surgery, and anesthesia; APACHE-II score; intraoperative average heart rate and blood loss; cumulative opioid use during surgery; patient age; VAS-Move-Median score on the 1st to 3rd day; Charlson comorbidity score; volumes of intraoperative plasma, crystalloid, and colloid fluids; cumulative red blood cell transfusion during surgery; and endotracheal intubation duration. Notably, our Random Forest model demonstrated exceptional performance with an accuracy of 0.9872.
CONCLUSION
We have developed and validated an algorithm for predicting PCCs in elderly patients by identifying key risk factors.
Aged
;
Aged, 80 and over
;
Female
;
Humans
;
Male
;
Middle Aged
;
Cardiovascular Diseases/etiology*
;
Machine Learning
;
Postoperative Complications/etiology*
;
Risk Factors
;
Randomized Controlled Trials as Topic
;
Secondary Data Analysis
7.Research on the Allocation Balance of Health Resources in Shanxi Province under the Background of Healthy Shanxi
Yimin KANG ; Juanjuan YAN ; Chaoshuo HE ; Miao WANG
Chinese Health Economics 2025;44(8):49-54,60
Objective:Under the background of the"Healthy Shanxi 2030"strategy,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province,and explores the optimization path to promote the high-quality development of health care.Methods:Based on the health statistics of Shanxi Province from 2012 to 2023,it systematically analyzes the spatiotemporal evolution characteristics and equilibrium of health resource allocation in Shanxi Province by using Gini coefficient,Theil index and statistical description method.Results:The total number of health resources in Shanxi Province continues to grow steadily,and by the end of 2023,the total number of medical and health institutions in the province will reach to 37 838,the number of hospital beds will reach to 223 650,and the total number of health technicians will be 260 536.Despite this,the imbalance of regional allocation is still significant,showing a"core-periphery"structure.According to the calculation of the Gini coefficient and the Theil index,from 2011 to 2023,the overall equilibrium of the health resources allocation in Shanxi Province showed a gradual improvement trend,which was reflected in the fact that the Gini coefficient of the number of health institutions decreased from 0.287 to 0.268,and the Theil index decreased by 42.40%.However,the structural imbalance of key human resources such as registered nurses is still significant,and the Gini coefficient continues to be higher than 0.30.The regional differences are mainly due to the economic gradient differentiation,policy orientation and population aging pressure,among which the Gini coefficient in the Jinzhong region group is 0.33,and the contribution of regional differences to the overall imbalance is more than 51.00%.Conclusion:Promote the balanced allocation of health resources and help achieve the strategic goal of"Healthy Shanxi"by optimizing the spatial distribution of resources,strengthening the capacity of grassroots services,improving the talent training and mobility mechanism,and deepening the reform of the hierarchical diagnosis and treatment system.
8.Discussion on the Effects of Hedysarum Polybotrys Polysaccharide on Glucose Metabolism of Small Intestinal Smooth Muscle in Diabetic Gastroparesis Rats with Spleen Qi Deficiency Syndrome Based on AMPK/GLUT4 Signaling Pathway
Wenwen WANG ; Zihui ZHONG ; Shengfang WAN ; Xinxin MA ; Lei ZHANG ; Miao LIU ; Minqi XUN ; Jinyu LI ; Kang FENG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(8):91-97
Objective To observe the effects of Hedysarum Polybotrys polysaccharide(HPS)on the glucose metabolism of small intestinal smooth muscle in rats with diabetic gastroparesis(DGP)of spleen qi deficiency syndrome;To explore its mechanism based on AMPK/GLUT4 signaling pathway.Methods Totally 72 male Wistar rats were randomly divided into 12 in the blank group and the remaining 60 rats were assigned to the model group.The DGP spleen qi deficiency syndrome model was replicated by intraperitoneal injection of streptozotocin+irregular feeding with high-fat and high sugar feed combined with swimming exhaustion method.The model rats were randomly divided into model group,metformin group and HPS high-,medium-and low-dosage groups.The metformin group was given 100 mg/kg metformin hydrochloride by gavage,while the HPS high-,medium-and low-dosage groups were given 200,100 and 50 mg/kg HPS by gavage,respectively.The blank group and model group were given purified water by gavage once a day for 8 consecutive weeks.The gastric emptying rate and small intestine propulsion rate in rats were detected,HE staining was used to observe the smooth muscle morphology of gastric antrum and ileal tissue,immunofluorescence staining was used to detect the expression of glucagon like peptide-1(GLP-1)in ileal tissue,ELISA was used to detect the contents of adiponectin(APN),glucagon(Glu)and insulin(INS)in serum,Western blot was used to detect the protein expressions of glucose transporter(GLUT)4,GLUT1,AMP-activated protein kinase(AMPK)and p-AMPK in ileal tissue.Results Compared with the blank group,the model group rats showed significantly increased random blood glucose,significantly decreased body mass,gastric emptying rate and small intestinal propulsion rate(P<0.01);the edema in the submucosal layer,loose arrangement of connective tissue,infiltration of a small number of lymphocytes,granulocytes and macrophages,reduced number of goblet cells in the ileal tissue,shedding of intestinal villous epithelial cells and widening of the gap between the submucosal layer and the lamina propria;the expression of GLP-1 in ileal tissue was significantly decreased(P<0.05),the contents of serum APN and INS were significantly decreased,and the content of Glu significantly increased(P<0.01),the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue were significantly decreased,while the expression of GLUT1 protein significantly increased(P<0.01).Compared with the model group,rats in metformin group and HPS high-dosage group showed a random decrease in blood glucose,an increase in body mass,gastric emptying rate,and small intestine propulsion rate(P<0.05,P<0.01);a more regular arrangement of gastric antral tissue cells,a reduction of shedding cells and edema,the smooth muscle structure of the ileal tissue was relatively intact,with evenly distributed cells and reduced infiltration of inflammatory cells;the expression of GLP-1 in ileal tissue increased,the contents of serum APN and INS increased,and the content of Glu decreased,the expressions of GLUT4 and p-AMPK/AMPK proteins in ileal tissue increased,while the expression of GLUT1 protein decreased(P<0.05,P<0.01).Conclusion HPS may up-regulate GLUT4 and down-regulate GLUT1 expression through activates AMPK,promotes glucose uptake and utilization by small intestinal smooth muscle,and improves glucose metabolism of DGP rats with spleen qi deficiency syndrome.
9.Safety and effectiveness of lecanemab in Chinese patients with early Alzheimer's disease: Evidence from a multidimensional real-world study.
Wenyan KANG ; Chao GAO ; Xiaoyan LI ; Xiaoxue WANG ; Huizhu ZHONG ; Qiao WEI ; Yonghua TANG ; Peijian HUANG ; Ruinan SHEN ; Lingyun CHEN ; Jing ZHANG ; Rong FANG ; Wei WEI ; Fengjuan ZHANG ; Gaiyan ZHOU ; Weihong YUAN ; Xi CHEN ; Zhao YANG ; Ying WU ; Wenli XU ; Shuo ZHU ; Liwen ZHANG ; Naying HE ; Weihuan FANG ; Miao ZHANG ; Yu ZHANG ; Huijun JU ; Yaya BAI ; Jun LIU
Chinese Medical Journal 2025;138(22):2907-2916
INTRODUCTION:
Lecanemab has shown promise in treating early Alzheimer's disease (AD), but its safety and efficacy in Chinese populations remain unexplored. This study aimed to evaluate the safety and 6-month clinical outcomes of lecanemab in Chinese patients with mild cognitive impairment (MCI) or mild AD.
METHODS:
In this single-arm, real-world study, participants with MCI due to AD or mild AD received biweekly intravenous lecanemab (10 mg/kg). The study was conducted at Hainan Branch, Ruijin Hospital Shanghai Jiao Tong University School of Medicine. Patient enrollment and baseline assessments commenced in November 2023. Safety assessments included monitoring for amyloid-related imaging abnormalities (ARIA) and other adverse events. Clinical and biomarker changes from baseline to 6 months were evaluated using cognitive scales (mini-mental state examination [MMSE], montreal cognitive assessment [MoCA], clinical dementia rating-sum of boxes [CDR-SB]), plasma biomarker analysis, and advanced neuroimaging.
RESULTS:
A total of 64 patients were enrolled in this ongoing real-world study. Safety analysis revealed predominantly mild adverse events, with infusion-related reactions (20.3%, 13/64) being the most common. Of these, 69.2% (9/13) occurred during the initial infusion and 84.6% (11/13) did not recur. ARIA-H (microhemorrhages/superficial siderosis) and ARIA-E (edema/effusion) were observed in 9.4% (6/64) and 3.1% (2/64) of participants, respectively, with only two symptomatic cases (one ARIA-E presenting with headache and one ARIA-H with visual disturbances). After 6 months of treatment, cognitive scores remained stable compared to baseline (MMSE: 22.33 ± 5.58 vs . 21.27 ± 4.30, P = 0.733; MoCA: 16.38 ± 6.67 vs . 15.90 ± 4.78, P = 0.785; CDR-SB: 2.30 ± 1.65 vs . 3.16 ± 1.72, P = 0.357), while significantly increasing plasma amyloid-β 42 (Aβ42) (+21.42%) and Aβ40 (+23.53%) levels compared to baseline.
CONCLUSIONS:
Lecanemab demonstrated a favorable safety profile in Chinese patients with early AD. Cognitive stability and biomarker changes over 6 months suggest potential efficacy, though high dropout rates and absence of a control group warrant cautious interpretation. These findings provide preliminary real-world evidence for lecanemab's use in China, supporting further investigation in larger controlled studies.
REGISTRATION
ClinicalTrials.gov , NCT07034222.
Humans
;
Alzheimer Disease/drug therapy*
;
Male
;
Female
;
Aged
;
Middle Aged
;
Cognitive Dysfunction/drug therapy*
;
Aged, 80 and over
;
Amyloid beta-Peptides/metabolism*
;
Biomarkers
;
East Asian People
10.Effects of Oral Chinese Patent Medicine Combined with Hormone Replacement Therapy in Improving Ovarian Hypofunction:A Systematic Review and Network Meta-analysis
Jing MIAO ; Zhiyuan KANG ; Haiyin HU ; Baihan NIU ; Zhaochen JI
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(1):235-254
Objective To systematically evaluate and compare the efficacy and safety of different oral Chinese patent medicine combined with hormone replacement therapy(HRT)in the treatment of ovarian hypofunction related diseases.Methods Relevant randomized controlled studies on Chinese patent medicine combined with HRT for the treatment of premature ovarian insufficiency,diminished ovarian reserve,premature ovarian failure were systematically searched in CNKI,WanFang,VIP,SinoMed,PubMed,and WOS databases,and the network Meta-analysis was performed using R 4.1.0 software.Results Eighty-three randomized controlled studies were included,with 3819 cases in the control group and 3844 cases in the experimental group,involving a total of 14 Chinese patent medicine(Kuntai capsule,Peikun pill,Zuogui pill,Heche Dazao capsule,Zishen Yutai pill,Fuke Yangrong capsule,Liuwei Dihuang pill,Rentaipan tablet,Guishen pill,Huanshao capsule,Qilin pill,Tiaojing Cuyun pill,Fufang Ejiao plasma,and Zuogui pill+Ruogui pill).The results of network Meta-analysis showed that:①Lowering of follicle stimulating hormone:the top 3 in the ranking were Zishen Yutai pill,Liuwei Dihuang pill,Fuke Yangrong capsule combined with HRT.② Increasing antral follicle counting:the top 3 in the ranking were Zuogui pill,Fuke Yangrong capsule,Zuogui pill+Ruogui pill combined with HRT.③Elevating of anti-Müllerian tube hormones:the top 3 in the ranking were Rentaipan tablet,Liuwei Dihuang pill,Kuntai capsule combined with HRT.④ Lowering Kupperman's score:the top 1 in the ranking was Kuntai capsule+HRT.⑤ Increasing in overall efficiency:the top 3 in the ranking were Fufang Ejiao plasma+HRT,Guishen pill+HRT,Zishen Yutai pill+HRT.The adverse events of combined HRT with oral Chinese patent medicine were mainly gastrointestinal discomfort,dizziness and headache,breast distension and pain.Conclusion The combination of oral Chinese patent medicine with HRT can better improve ovarian function and alleviate perimenopausal symptoms.For patients with fertility requirements,priority should be given to Fuke Yangrong capsule or Liuwei Dihuang pill combined with HRT to improve FSH levels and increase follicular reserve.For patients with obvious perimenopausal symptoms,priority should be given to Kuntai capsule combined with HRT to alleviate the symptoms.And Fufang Ejiao plasma,Guishen pill,Zishen Yutai pill combined with HRT should be given to increase the overall effective rate of the treatment.


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