1.Role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 and effect of Bushen Jianpi Huoxue Decoction.
Tong-Ying CHEN ; Sai FU ; Xiao-Yun LI ; Shu-Hua LIU ; Yi-Fu YANG ; Dong-Sheng YANG ; Yun-Jie ZENG ; Yang-Bo LI ; Dan LUO ; Hong-Xing HUANG ; Lei WAN
China Journal of Chinese Materia Medica 2025;50(3):583-589
Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism*
;
Autophagy/drug effects*
;
Apoptosis/drug effects*
;
Humans
;
Drugs, Chinese Herbal/administration & dosage*
;
Animals
;
Cell Line
;
bcl-X Protein/metabolism*
;
Osteoblasts/metabolism*
;
Rats
;
Osteoporosis/physiopathology*
;
Male
;
Rats, Sprague-Dawley
;
Osteogenesis/drug effects*
2.Salvianolic Acid B Exerts Antiphotoaging Effect on Ultraviolet B-Irradiated Human Keratinocytes by Alleviating Oxidative Stress via SIRT1 Protein.
Qiao-Ju ZHANG ; Xi LUO ; Yu-Wen ZHENG ; Jun-Qiao ZHENG ; Xin-Ying WU ; Shu-Mei WANG ; Jun SHI
Chinese journal of integrative medicine 2025;31(11):1021-1028
OBJECTIVE:
To explore the anti-photoaging properties of salvianolic acid B (Sal B).
METHODS:
The optimal photoaging model of human immortalized keratinocytes (HaCaT cells) were constructed by expose to ultraviolet B (UVB) radiation. The cells were divided into control, model and different concentrations of Sal B groups. Cell viability was measured via cell counting kit-8. Subsequently, the levels of oxidative stress, including reactive oxygen species (ROS), hydroxyproline (Hyp), catalase (CAT), and glutathione peroxidase (GSH-Px) were detected using the relevant kits. Silent information regulator 1 (SIRT1) protein level was detected using Western blot. The binding pattern of Sal B and SIRT1 was determined via molecular docking.
RESULTS:
Sal B significantly increased the viability of UVB-irradiated HaCaT cells (P<0.05 or P<0.01). Sal B effectively scavenged the accumulation of ROS induced by UVB (P<0.05 or P<0.01). In addition, Sal B modulated oxidative stress by increasing the intracellular concentrations of Hyp and CAT and the activity of GSH-Px (P<0.05 or P<0.01). The Western blot results revealed a substantial increase in SIRT1 protein levels following Sal B administration (P<0.05). Moreover, Sal B exhibited good binding affinity toward SIRT1, with a docking energy of -7.5 kCal/mol.
CONCLUSION
Sal B could improve the repair of photodamaged cells by alleviating cellular oxidative stress and regulating the expression of SIRT1 protein.
Humans
;
Sirtuin 1/metabolism*
;
Ultraviolet Rays
;
Oxidative Stress/radiation effects*
;
Keratinocytes/metabolism*
;
Molecular Docking Simulation
;
Benzofurans/pharmacology*
;
Skin Aging/radiation effects*
;
Reactive Oxygen Species/metabolism*
;
Cell Survival/radiation effects*
;
HaCaT Cells
;
Hydroxyproline/metabolism*
;
Glutathione Peroxidase/metabolism*
;
Catalase/metabolism*
;
Depsides
3.Analysis of factors influencing frequent episodes in children with moderate-to-severe atopic dermatitis: a national multicenter cross-sectional study
Jing TIAN ; Yifeng GUO ; Xiaoyan LUO ; Yuan LIANG ; Ping LI ; Jinping CHEN ; Yao LU ; Jianping TANG ; Yunsheng LIANG ; Ying GAO ; Qiufang QIAN ; Hong SHU ; Hongxiang CHEN ; Pingshen FAN ; Xiuping HAN ; Hua QIAN ; Qinfeng LI ; Ming LI ; Shengchun WANG ; Ying LIU ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(10):943-951
Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.
4.Manufacture and mechanical property on zirconia abutments with a titanium base in dental implant restoration
Huan WANG ; Jing LU ; Ying LI ; Maohua MENG ; Jiayu SHU ; Yuncai LUO ; Wenjie LI ; Qiang DONG
Chinese Journal of Tissue Engineering Research 2025;29(10):2171-2177
BACKGROUND:With the development of computer-aided design and computer-aided manufacturing technology,zirconia abutments with a titanium base are widely used in clinic due to its good application advantages,but there are still some problems and a lack of consensus design standards. OBJECTIVE:To review the fabrication methods of Ti-base zirconia abutment,and the effect of abutment connection,emergence design,abutment angle,and bonding on mechanical properties of Ti-base zirconia abutment. METHODS:Relevant literature published from 2010 to 2023 was searched in CNKI and PubMed databases with the search terms"zirconia abutment,titanium base"in Chinese and English,respectively.The search time limit was extended for some classical literature.The relevant literature was obtained through inclusion and exclusion criteria,and 57 eligible documents were included for review. RESULTS AND CONCLUSION:It is recommended that clinicians try to select antirotational titanium bases or rotational titanium bases with a Morse taper connection.Implants should be placed in the correct axial angulation of not more than 15° or with an inclination to the palatal side when using angled zirconia abutments.When a≥30° labial inclination is followed for implant placement,the bite force must be decreased effectively to reduce the risk of mechanical and biological complications of implants,abutments,and prostheses.Ti-base zirconia abutments with a higher gingival height should be selected,and its restorative angle should not exceed 40°.Multilink Hybrid Abutment could be the first choice for extraoral bonding of zirconia abutment to titanium bases.
5.The Role of APOE in Drug Resistance of Colon Cancer Based on Bioinformatics and Cell Experiments
Ruo SHU ; Huayou LUO ; Lijun SONG ; Yu GAO ; Yan HOU ; Xinfeng ZHANG ; Ying LI
Journal of Kunming Medical University 2025;46(9):15-22
Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.
6.The safety and efficacy of boron neutron capture therapy (BNCT) in the treatment of recurrent malignant tumors
Junqiang HONG ; Xiaoyi LIN ; Youqun LAI ; Ye CAO ; Xiangquan KONG ; Yuanhao LIU ; Shuiying LUO ; Zhicheng XIONG ; Mei GONG ; Yalai LIN ; Qiaoyun CHEN ; Mingang YING ; Li HUO ; Xiaohua ZHU ; Xiaoping SUN ; Yiqiao DENG ; Diyun SHU ; Haige ZHANG ; Cheng HUANG ; Jianji PAN
Chinese Journal of Radiation Oncology 2025;34(10):985-992
Objective:To evaluate the safety and efficacy of accelerator-based boron neutron capture therapy (AB-BNCT) in the treatment of recurrent and refractory malignant tumors.Methods:The data of 14 patients admitted to Xiamen Humanity Hospital from September 2022 to April 2023 were prospectively collected, including 7 patients with primary brain malignancies and 7 patients with locally recurrent inoperable head and neck malignancies. All patients received intravenous infusion of boron drug (NBB-001, p-dihydroxyborylphe nylalanine, a patented freeze-dried formulation) at a total nominal dosage of 500 mg/kg (11 patients) or 750 mg/kg (3 patients), and were irradiated with neutrons (operating with NeuPex system). Adverse events after treatment were recorded and assessed. The primary efficacy endpoint was the 90 d objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS) and complete response rate (CRR). Data were compiled and analyzed by SAS 9.4 software. The rate and 95% CI were calculated using Clopper-Pearson method. Results:The median dose delivered to 80% of the target volume (D 80%) was 16.80 GyE (range: 8.93-23.79 GyE). The most common adverse reactions were hyperamylasemia, alopecia, and hyperprolactinemia. Five patients experienced 8 cases of grade 3 or above adverse events, including 1 case of grade 4 acute kidney injury and 7 cases of grade 3 adverse events. All adverse events were recovered after observation or treatment. At 90 d after treatment, the ORR of all patients was 9/14 (64%, 95% CI: 35%-87%), disease control rate (DCR) was 10/14 (71%, 95% CI: 42%-92%), CRR was 2/14 (14%, 95% CI: 2%-42%); and the best overall response during the entire course included an ORR of 10/14 (71% ,95% CI: 42%-92%), DCR of 13/14 (93%, 95% CI: 66%-100%), and CRR of 3/14 (21% ,95% CI: 5%-51%). The 1-year survival rate for head and neck malignancies was 71.4%, and the 2-year survival rate was 42.8%. The 1-year survival rate for recurrent brain malignancies was 42.8%. Conclusion:AB-BNCT demonstrates favorable safety and promising efficacy in treating primary brain malignancies and recurrent/refractory head and neck malignancies, representing a potential therapeutic option.
7.Copper influences the occurrence and development of diabetic complications
Yuncai LUO ; Maohua MENG ; Ying LI ; Huan WANG ; Jing LU ; Jiayu SHU ; Wenjie LI ; Jinyi SUN ; Qiang DONG
Chinese Journal of Tissue Engineering Research 2025;29(17):3641-3649
BACKGROUND:As an essential trace element for body growth and development,copper participates in many processes such as redox process,energy generation,signal transduction and bone metabolism.The imbalance of copper homeostasis in diabetic patients will lead to the increase of oxidative stress and the impairment of antioxidant mechanism,which stimulate the production of inflammatory mediators and inflammatory factors,and thus lead to cytotoxicity and body damage.In recent years,the role of copper in diabetes has gradually attracted attention,and some studies have confirmed that copper plays a key regulatory role in the pathological process of diabetes.OBJECTIVE:To summarize the current progress in the role of copper in systemic complications of diabetes and provide some theoretical reference for its future research and treatment.METHODS:The first author searched PubMed,Web of Science,CNKI and WanFang databases for literature related to the role of copper in systemic complications of diabetes.The search terms were"copper,Cu,diabetes,diabetic complications,diabetic cardiomyopathy,diabetic nephropathy,diabetic retinopathy,diabetic osteoporosis,diabetic periodontitis"in English and Chinese,respectively.After screening,95 articles were included in the review.RESULTS AND CONCLUSION:(1)Copper is involved in the occurrence and development of diabetic complications and most of the damage caused by copper to the body is due to interference with the body's redox level.(2)In diabetic cardiomyopathy,increased Cu2+in the corpuscular circulation and impaired uptake of copper ions by cardiomyocytes,the accumulation of redox-active Cu2+and ceruloplasmin outside the cardiomyocyte induces copper oxidative stress in cardiomyocytes,leading to acute cardiac impairment.(3)In diabetic nephropathy,the toxic effect of excessive copper leads cause granular degeneration and vacuolar degeneration of renal tubular epithelial cells and proximal tubular necrosis,eventually leading to chronic or acute renal failure.(4)Excessive copper in diabetic patients can produce reactive oxygen species and directly or indirectly affect the function of copper protein with antioxidant function,thus damaging retinal cells.(5)In patients with diabetic osteoporosis,accumulated copper induces lipid peroxidation and interferes with bone metabolism.Copper acts on osteoblasts mainly through inhibition of superoxide dismutase,glutathione peroxidase,and alkaline phosphatase activities.(6)Excessive copper exacerbates inflammatory changes in periodontal tissue by promoting inflammatory responses.
8.Association between insulin resistance and idiopathic central precocious puberty in girls and the diagnostic value of insulin resistance
Jin-Bo LI ; Ya XIAO ; Shu-Qin JIANG ; Xiang-Yang LUO ; Hong-Ru ZHANG ; Jun SUN ; Wen-Hui SHI ; Ying YANG ; Wei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(12):1487-1492
Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.
9.Analysis of factors influencing frequent episodes in children with moderate-to-severe atopic dermatitis: a national multicenter cross-sectional study
Jing TIAN ; Yifeng GUO ; Xiaoyan LUO ; Yuan LIANG ; Ping LI ; Jinping CHEN ; Yao LU ; Jianping TANG ; Yunsheng LIANG ; Ying GAO ; Qiufang QIAN ; Hong SHU ; Hongxiang CHEN ; Pingshen FAN ; Xiuping HAN ; Hua QIAN ; Qinfeng LI ; Ming LI ; Shengchun WANG ; Ying LIU ; Hua WANG ; Lin MA
Chinese Journal of Dermatology 2025;58(10):943-951
Objective:To investigate factors influencing frequent episodes (≥ 4 episodes within 1 year) in children with moderate-to-severe atopic dermatitis (AD) in China.Methods:A national multicenter cross-sectional study was conducted. Patients under the age of 18 years diagnosed with moderate-to-severe AD were enrolled at dermatology clinics in 18 medical institutions across 12 provinces and municipalities in China between June 12 and August 8, 2023. At the time of the visit, their guardians completed a structured questionnaire covering demographic characteristics, clinical features of AD, personal and family history, factors associated with frequent episodes of moderate-to-severe AD, compliance with treatment, and disease awareness. Statistical analyses included t tests, one-way analysis of variance, rank-sum tests, and chi-square tests, with multiple-response analysis applied for multiple-choice questions. Results:A total of 965 valid questionnaires were collected, and 965 children with moderate-to-severe AD were included. Among them, there were 531 males and 434 females, 678 (70.3%) were aged 2 - < 12 years, 837 (86.7%) were from urban areas, the age at onset was 2.47 ± 3.03 years, and the median frequency of AD episodes in the past year was 4 times. These children were divided into 2 groups based on the median episode frequency: < 4-episode group (439 cases, 45.5%) and ≥ 4-episode group (526 cases, 54.5%). Compared with the < 4-episode group, children in the ≥ 4-episode group showed younger ages at onset (2.22 ± 2.98 years vs. 2.76 ± 3.06 years, P = 0.006) and higher proportions of patients with comorbid allergic diseases in both the children themselves (82.9% [436/526] vs. 69.7% [306/439], χ2 = 23.42, P < 0.001) and their relatives (66.0% [347/526] vs. 57.4% [252/439], χ2 = 7.46, P = 0.006). Children in the ≥ 4- episode group also had higher monthly usage of moisturizers (150 [30, 300] g vs. 60 [6, 200] g) and daily frequency of moisturizer use, greater disease awareness, but more severe fear of medication use (all P < 0.05). The region and the human development index level were both significantly associated with the episode frequency (both P < 0.001), with the highest proportion of children from South China in the ≥ 4- episode group (36.3%, 191/526). Children in the ≥ 4-episode group also had a longer duration of topical glucocorticoid use than those in the < 4-episode group ( Z = -2.21, P = 0.027). External triggers associated with AD episodes mainly included heat exposure (50.36%, 486/965), hot water bathing (40.73%, 393/965), seafood (23.52%, 227/965), and dust mites (33.37%, 322/965) . Conclusion:In children with moderate-to-severe AD in China, factors influencing frequent episodes may include residence in southern or economically developed regions, earlier age at onset, having a personal or family history of allergic diseases, and fear of medication use.
10.Association between insulin resistance and idiopathic central precocious puberty in girls and the diagnostic value of insulin resistance
Jin-Bo LI ; Ya XIAO ; Shu-Qin JIANG ; Xiang-Yang LUO ; Hong-Ru ZHANG ; Jun SUN ; Wen-Hui SHI ; Ying YANG ; Wei WANG
Chinese Journal of Contemporary Pediatrics 2025;27(12):1487-1492
Objective To explore the relationship between insulin resistance and idiopathic central precocious puberty(ICPP)in girls and the diagnostic value of insulin resistance.Methods Clinical data of 245 girls aged 4 to 7.5 years with low luteinizing hormone(LH)levels(0.2-0.83 IU/L),normal body weight(body mass index standard deviation score between-2 and+2),and early breast development who visited the Department of Pediatric Endocrinology,Henan Provincial Maternal and Child Health Hospital from January 2022 to March 2025 were retrospectively analyzed.According to the Expert Consensus on the Diagnosis and Treatment of Central Precocious Puberty(2022),patients were assigned to an ICPP group(n=123)or a control group(n=122).Correlations between the homeostasis model assessment of insulin resistance(HOMA-IR)and selected indices were assessed.Multivariable logistic regression was used to evaluate the association between HOMA-IR and ICPP,and the diagnostic performance of various indices for ICPP was evaluated.Results HOMA-IR was higher in the ICPP group than in the control group(P<0.001)and was positively correlated with LH peak(rs=0.467,P<0.05)and the LH peak/FSH peak ratio(rs=0.444,P<0.05).The multivariable logistic regression model including age,BMI,and basal LH showed that HOMA-IR was closely associated with ICPP(OR=2.756,95%CI:1.940-3.913).Receiver operating characteristic curve analysis showed that the areas under the curve for basal LH,HOMA-IR,and their combination in diagnosing ICPP were 0.735,0.735,and 0.805,respectively(P<0.05),and the combined model had a greater area under the curve than either basal LH or HOMA-IR alone(both P<0.05).Conclusions HOMA-IR is closely associated with ICPP in girls with low LH and normal body weight,and combining HOMA-IR with basal LH improves early identification and diagnostic efficiency in this population.

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