OBJECTIVE To evaluate the cost-effectiveness of rezivertinib versus gefitinib as first-line treatment for epidermal growth factor receptor （EGFR） mutation-positive advanced non-small cell lung cancer （NSCLC） from the perspective of the Chinese healthcare system. METHODS A Markov model was constructed based on the REZOR trial data， with a cycle length of 3 weeks and a study duration of 5 years. Both costs and health outcomes were discounted at an annual rate of 5%. A cost-utility analysis was conducted using 3 times China’s 2024 per capita gross domestic product as the willingness-to-pay （WTP） threshold. The economic differences between the rezivertinib regimen versus the gefitinib regimen were evaluated using the incremental cost- effectiveness ratio （ICER） and incremental net monetary benefit （INMB）. Sensitivity and scenario analyses were performed to verify the robustness of the model. RESULTS Compared to the gefitinib regimen， the rezivertinib regimen saved 225 310.47 yuan and gained an additional 0.57 quality- adjusted life years （QALYs）， resulting in an ICER of －395 562.80 yuan/QALY， which was much lower than the WTP threshold of this study， indicating that rezivertinib had an absolute economic advantage. The INMB analysis （389 041.26 yuan） further validated this conclusion. One-way and probabilistic sensitivity analyses confirmed the robustness of the model. Scenario analysis， incorporating a 15% reduction in drug prices and adjustments to the utility values for progression free survival and progression disease， yielded consistent results with the base case analysis. CONCLUSIONS Compared to gefitinib， rezivertinib as a first-line treatment for EGFR mutation-positive advanced NSCLC has an absolute economic advantage.

ObjectiveTo develop a novel clinical predictive model for metabolic dysfunction-associated fatty liver disease （MAFLD） based on metabolic markers and anthropometric indicators， and to provide a more effective tool for the early screening and intervention of MAFLD. MethodsA retrospective analysis was performed for 2 824 individuals who underwent abdominal color Doppler ultrasound at Health Examination Center of The First Hospital of Lanzhou University from January 1， 2024 to January 1， 2025， and at a ratio of 7∶3， they were randomly divided into training set with 1 976 patients and validation set with 848 patients. Clinical data， serological markers， and abdominal ultrasound results were collected from all patients， and triglyceride-glucose （TyG） index， triglyceride-to-high-density lipoprotein cholesterol （TG/HDL-C） ratio， and anthropometric indicators were calculated. The independent samples t-test was used for comparison of normally distributed or approximately normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between groups. The multivariate logistic regression analysis was used to identify independent predictive factors for MAFLD and intermediate- to high-risk MAFLD. Five risk prediction models were established for MAFLD based on the independent influencing factors， and a nomogram was plotted. The receiver operating characteristic （ROC） curve was plotted to assess model performance， and the area under the ROC curve （AUC） was calculated. The calibration curve was used to evaluate the predictive accuracy of the models， and decision curve analysis was used to assess the clinical practicability of the models. These models were then compared with traditional models. ResultsAmong the 1 976 individuals in the training set， 937 （47.42%） were diagnosed with MAFLD， and 423 （21.41%） were diagnosed with intermediate- to high-risk MAFLD； among the 848 individuals in the validation set， 406 （47.88%） were diagnosed with MAFLD. The multivariate logistic regression analysis showed that male sex （odds ratio ［OR］=0.23， 95% confidence interval ［CI］： 0.13 — 0.39， P<0.05）， waist circumference （OR=1.11， 95%CI： 1.06 — 1.17， P<0.05）， alanine aminotransferase （ALT） >40 U/L （OR=2.24， 95%CI： 1.44 — 3.51， P<0.05）， high-density lipoprotein cholesterol （HDL-C） （OR=0.07， 95%CI： 0.04 — 0.15， P<0.05）， TyG index （OR=8.27， 95%CI： 5.09 — 13.44， P<0.05）， TG/HDL-C ratio （OR=0.84， 95%CI： 0.71 — 0.99， P<0.05）， A Body Shape Index （ABSI） （OR=0.45， 95%CI： 0.39 — 0.52， P<0.05）， and body roundness index （BRI） （OR=2.31， 95%CI： 1.50 — 3.55， P<0.05） were independent influencing factors for MAFLD， and male sex （OR=0.17， 95%CI： 0.10 — 0.31， P<0.05）， age （OR=1.09， 95%CI： 1.07 — 1.11， P<0.05）， hemoglobin （OR=0.98， 95%CI： 0.97 — 0.98， P<0.05）， platelet count （OR=0.81， 95%CI： 0.70 — 0.93， P<0.05）， fasting blood glucose （OR=0.80， 95%CI： 0.71 — 0.89， P<0.05）， triglycerides （OR=0.14， 95%CI： 0.07 — 0.29， P<0.05）， TG/HDL-C ratio （OR=0.78， 95%CI： 0.67 — 0.91， P<0.05）， TyG index （OR=5.26， 95%CI： 3.32 — 8.33）， waist circumference （OR=2.50， 95%CI： 1.72 — 3.61， P<0.05）， ABSI （OR=0.58， 95%CI： 0.51 — 0.66， P<0.05）， and BRI （OR=0.01， 95%CI： 0.00 — 0.21， P<0.05） were independent influencing factors for intermediate- to high-risk MAFLD. Among the five models established， model 5 （incorporating sex， ALT elevation， HDL-C， TyG index， TG/HDL-C ratio， waist circumference， and ABSI） had the best performance， with an AUC of 0.917 （95%CI： 0.905 — 0.929） in the training set and 0.911 （95%CI： 0.892 — 0.930） in the validation set. The calibration curve showed that model 5 had good predictive accuracy， and the decision curve analysis confirmed its clinical practicability. ConclusionThe predictive model for MAFLD constructed based on metabolic markers and anthropometric indicators has good discriminatory ability and can be used to assess the risk of MAFLD. In addition， this study shows that waist circumference， TyG index， TG/HDL-C ratio， ABSI， and BRI are independently associated with intermediate- to high-risk MAFLD， but further studies are needed to confirm their value in predicting liver fibrosis progression.

Objective To explore the effect and mechanism of Gegen Qinlian decoction (GQD) on myocardial injury induced by high-fat diet combined with streptozotocin in type 2 diabetic mice through network pharmacology and animal experiments. MethodsNetwork pharmacology was applied to screen the potential signaling pathways of GQD in the intervention of diabetic heart disease (DHD). A total of 36 specific pathogen-free (SPF) male C57BL/6J mice aged 8 weeks were acclimatized for 1 week and randomly divided into a normal control group (n=6) and a model group (n=30). Mice in the model group were fed a 60% high-fat diet and 5% glucose water for 4 weeks, and were intraperitoneally injected with 100 mg/kg streptozotocin after 12 h of fasting to establish the type 2 diabetes model. Mice in the normal control group were given a conventional diet and drinking water, and were intraperitoneally injected with an equal volume of citrate buffer after 12 h of fasting at the same time point. After successful establishment of the diabetic mouse model, the model mice were randomly divided into five groups according to body weight: model control group, GQD low-dose group, GQD medium-dose group, GQD high-dose group, and metformin positive control group, with 6 mice in each group. After 6 weeks of intragastric administration of corresponding doses of GQD, metformin, and ddH₂O respectively, all mice in the six groups (one normal control group and five model groups) were anesthetized with inhaled 2% isoflurane, blood samples were collected via eyeball enucleation, and heart tissues were harvested after euthanasia by cardiac exsanguination. Hematoxylin-eosin (HE) staining and wheat germ agglutinin (WGA) staining were performed to observe the pathological damage of myocardial tissues and measure the cross-sectional area of cardiomyocytes. Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of pro-inflammatory cytokines in serum. Immunohistochemical staining was adopted to determine the protein expression levels of receptor for advanced glycation end products (RAGE), nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), and phosphorylated nuclear factor-κB p65 (p-p65) in myocardial tissues. ResultsNetwork pharmacology analysis revealed that the targets of GQD against DHD were significantly enriched in inflammatory pathways, including the advanced glycation end products (AGEs)-RAGE axis, tumor necrosis factor (TNF) and interleukin-17 (IL-17) signaling pathways. HE and WGA staining results showed that, compared with the normal control group, the model control group exhibited myocardial fiber rupture, cardiomyocyte swelling, and significantly increased cardiomyocyte cross-sectional area (P<0.05). Compared with the model control group, GQD intervention significantly ameliorated the pathological changes, including myocardial fiber rupture, cell swelling, and cardiomyocyte hypertrophy. The results of immunohistochemical staining and ELISA indicated that compared with the model control group, GQD intervention markedly downregulated the protein expression of RAGE, NLRP3, and p-p65 in myocardial tissues, as well as the levels of serum pro-inflammatory cytokines (P<0.05). ConclusionGQD can effectively alleviate myocardial pathological injury in diet-induced type 2 diabetic mice, and its mechanism may be related to inhibiting the activation of the RAGE/p-p65/NLRP3 signaling pathway and reducing myocardial inflammatory response.

BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.

BACKGROUND:We have successfully established an animal model of small ear pig in southern Yunnan province with internal tension relieving technique combined with autologous Achilles tendon for anterior cruciate ligament reconstruction,and verified the stability and reliability of the model.However,whether internal tension relieving technique can promote the ligamentalization process of autologous Achilles tendon graft has not been studied. OBJECTIVE:To investigate the differences in the process of ligamentalization between conventional reconstruction and internal reduction reconstruction of the anterior cruciate ligament by gross view,histology and electron microscopy. METHODS:Thirty adult female small ear pigs in southern Yunnan province were selected.Anterior cruciate ligament reconstruction was performed on the left knee joint with the ipsilateral knee Achilles tendon(n=30 in the normal group),and anterior cruciate ligament reconstruction was performed on the right knee joint with the ipsilateral knee Achilles tendon combined with the internal relaxation and enhancement system(n=30 in the relaxation group).The autogenous right forelimb was used as the control group;the anterior cruciate ligament was exposed but not severed or surgically treated.At 12,24,and 48 weeks after surgery,10 animals were sacrificed,respectively.The left and right knee joint specimens were taken for gross morphological observation to evaluate the graft morphology.MAS score was used to evaluate the excellent and good rate of the ligament at each time point.Hematoxylin-eosin staining was used to evaluate the degree of ligament graft vascularization.Collagen fibers and nuclear morphology were observed,and nuclear morphology was scored.Ultrastructural remodeling was evaluated by scanning electron microscopy and transmission electron microscopy. RESULTS AND CONCLUSION:(1)The ligament healing shape of the relaxation group was better at various time points after surgery,and the excellent and good rate of MAS score was higher(P<0.05).Moreover,the relaxation group could obtain higher ligament vascularization score(P<0.05).(2)The arrangement of collagen bundles and fiber bundles in the two groups gradually tended to be orderly,and the transverse fiber connections between collagen gradually increased and thickened,suggesting that the strength and shape degree of the grafts were gradually improved,but the ligament remodeling in the relaxation group was always faster than that in the normal group at various time points after surgery.(3)The diameter,distribution density,and arrangement degree of collagen fibers in the relaxation group were better than those in the normal group at all time points,especially in the comparison of collagen fiber diameter between and within the relaxation group(P<0.05).

Objective: To investigate characteristics of colorectal cancer incidence and mortality in registration areas of Guangdong Province in 2020, so as to provide a basis for optimizing regional prevention and control strategies. Methods: Data on incidence and mortality of colorectal cancer in cancer registration areas of Guangdong Province in 2020 were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, truncated rate for 35 to 64 years, and cumulative rate for 0 to 64 years were calculated, and standardized using the Segi's world standard population. Descriptive epidemiological methods were applied to analyze the characteristics of colorectal cancer incidence and mortality by different genders, urban/rural areas and ages. Results: A total of 14 771 cases of colorectal cancer were reported in Guangdong Province in 2020. The crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 35.18/100 000, 24.84/100 000, 38.87/100 000 and 1.37%, respectively. A total of 5 384 deaths of colorectal cancer were reported, with crude incidence, world population-standardized incidence, truncated incidence for 35 to 64 years and cumulative incidence for 0 to 64 years were 14.55/100 000, 8.83/100 000, 10.39/100 000 and 0.37%, respectively. The crude incidence and mortality were higher in males than in females (40.35/100 000 vs. 29.88/100 000, 16.51/100 000 vs. 12.54/100 000, both P<0.05). The crude incidence and mortality were higher in urban areas than in rural areas (38.94/100 000 vs. 26.10/100 000, 16.60/100 000 vs. 10.42/100 000, both P<0.05). The crude incidence of colorectal cancer initially increased with advancing age (P<0.05), reaching a peak of 239.36/105 in the 80-<85 age group, followed by a marked decline after 85 years. The crude mortality of colorectal cancer increased with advancing age (P<0.05), reaching a peak of 174.25/100 000 in the ≥85 years age group. Conclusions In 2020, the incidence and mortality of colorectal cancer in registration areas of Guangdong Province were higher than the national averages. There were differences in the characteristics of incidence and mortality among genders, urban/areas and age. Therefore, it is necessary to strengthen the comprehensive prevention and control efforts for colorectal cancer in males, urban areas, and the elderly population.

Objective: To investigate the epidemiological characteristics of lung cancer in cancer registration areas of Guangdong Province in 2020, so as to provide the evidence for improving prevention and control strategies of lung cancer. Methods: Data of incidence and mortality in 2020 from 30 cancer registries in Guangdong Province were collected from the Cancer Follow-up Registration System and the All-Cause Mortality Registration Reporting System of the Guangdong Provincial Center for Disease Control and Prevention. The crude incidence, crude mortality, and cumulative rate for 0 to 74 years were calculated. The Chinese population-standardized rate and world population-standardized rate were calculated using the age structure of the standard population from the Fifth National Population Census in 2000 and Segi's world standard population. The incidence and mortality characteristics of lung cancer in different genders, urban/rural areas and ages were described. Results: In 2020, there were 25 357 new cases of lung cancer in Guangdong Province. The crude incidence, Chinese population-standardized incidence, world population-standardized incidence, and cumulative incidence for 0 to 74 years were 60.40/100 000, 43.75/100 000, 43.26/100 000, and 5.30%, respectively. There were 14 366 lung cancer deaths. The crude mortality, Chinese population-standardized mortality, world population-standardized mortality, and cumulative mortality for 0 to 74 years were 38.82/100 000, 24.49/100 000, 24.36/100 000, and 2.88%, respectively. The crude incidence and crude mortality of lung cancer in males were higher than those in females (71.19/100 000 vs. 49.42/100 000, 52.94/100 000 vs. 24.36/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer in urban areas were higher than those in rural areas (66.37/100 000 vs. 45.95/100 000, 40.68/100 000 vs. 35.07/100 000, both P<0.05). The crude incidence and crude mortality of lung cancer exhibited upward trends with increasing age (both P<0.05), peaking in the age of 80-<85 years (347.97/100 000 and 342.14/100 000). Conclusions Comparing to the national data, the incidence of lung cancer in registration areas of Guangdong Province remained relatively high, while mortality remained relatively low. Males, urban residents and the elderly constitute the key populations for lung cancer prevention and control. It is recommend to optimize the allocation of medical resources between urban and rural areas and strengthen lung cancer screening among high-risk groups.

Objective To explore the value of CT signs and quantitative parameters of artificial intelligence (AI) in predicting the efficacy of neoadjuvant chemotherapy for colorectal cancer. Methods A total of 349 colorectal cancer patients who received neoadjuvant chemotherapy at Cangzhou Hospital of Integrated Traditional Chinese and Western Medicine in Hebei Province from January 2022 to January 2025 were selected and and divided into the effective group (n = 267) and the ineffective group (n = 82) according to the evaluation criteria for the efficacy of solid tumors. Conduct a CT examination and extract AI quantitative parameters from the CT images based on the lesion. The data were analyzed using SPSS21.0 software, Logistic regression was used to screen the influencing factors of ineffective neoadjuvant chemotherapy in patients with colorectal cancer, and separate and combined models of CT signs and AI quantitative parameters were established. The predictive effect of the model was verified by using the ROC curve, calibration curve and decision curve. Results Compared with the effective group, the proportion of regular tumor morphology and the proportion of non-enlarged lymph nodesin the ineffective group were smaller. The tumor volume, peak value and entropy value were larger (P < 0.05). Multivariable analysis showed that irregular shape (OR= 4.216), presence of lymph node enlargement (OR = 8.998), larger tumor volume (OR = 1.109), higher average CT value (OR = 1.120), elevated peak value (OR = 2.528), and increased entropy value (OR = 1.390) were independent risk factors for ineffective neoadjuvant chemotherapy in colorectal cancer (P < 0.05). The areas under the ROC curves of the individual and combined models of CT signs and AI quantitative parameters were 0.777, 0.818, and 0.877, respectively(P < 0.05). The calibration curve showed a Brier score of 0.091. The decision curve showed that the threshold was between 0.10 and 0.85, and the combined model achieved a relatively high net clinical benefit. Conclusion CT signs combined with AI quantitative parameters has a predictive value for the efficacy of neoadjuvant chemotherapy in colorectal cancer. To provide evidence-based basis for clinical screening of the population benefiting from chemotherapy and optimization of treatment strategies.

Objective:To evaluate the application effect of improved problem-based learning (PBL) based on 5W2H thinking in the course of "massage therapy".Methods:The undergraduate students in Class 1 and Class 2 of Acupuncture and Massage in the first semester of the 2023-2024 academic year at Heilongjiang University of Chinese Medicine were selected as the research subjects. The "massage therapy" was taught in Class 1 with the traditional method (control group, n=66) and in Class 2 with the method of improved PBL with 5W2H thinking (observation group, n=68). The two groups of students were compared in terms of theoretical knowledge of massage therapy, the assessment of massage skills, comprehensive ability, innovation ability, and practical ability, as well as the procedural evaluation indicators of massage. SPSS 25.0 was used for normality test and t test χ2 test. Results:After the completion of the study, the observation group showed higher scores in theoretical knowledge (90.56±11.73), massage skill proficiency [(87.22±11.57) vs. (78.23±9.45)], massage skill demonstration [(84.56±11.20) vs. (74.69±9.13)], mannequin usage [(82.98±10.75) vs. (72.66±8.89)], and massage skill mechanics [(86.38±11.45) vs. (73.35±8.94)] compared to the control group. The observation group also outperformed the control group in medical humanities [(85.53±10.64) vs. (64.86±7.33)], teacher-student and student-student interaction [(85.35±8.67) vs. (80.15±7.46)], clinical thinking and operation [(90.05±12.13) vs. (74.26±8.94)], and team coordination and cooperation [(85.60±10.06) vs. (81.53±9.33)]. In addition, the observation group scored higher than the control group in learning participation rate [(18.20±3.75) vs. (13.15±2.93)], error correction rate [(27.56±5.85) vs. (22.11±4.62)], operational stability [(48.43±7.79) vs. (42.06±6.60)], and total score [(94.19±7.56) vs. (77.32±6.78)].Conclusions:The application of improved PBL based on 5W2H thinking in the course of "massage therapy" has significant clinical implications. It can not only improve the teaching quality and effect, but also cultivate students' clinical thinking, teamwork, learning interest, and innovation ability, making it suitable for further promotion and application.

Objective:To analyze the epidemic characteristics of human brucellosis in Inner Mongolia Autonomous Region, and to provide a basis for formulating targeted intervention strategies and implementation measures.Methods:The data of brucellosis cases with onset date from 2014 to 2023 and current address in Inner Mongolia Autonomous Region were collected from the Chinese Disease Control and Prevention Information System. Descriptive epidemiological method was used to analyze the three-dimensional distribution of human brucellosis in Inner Mongolia Autonomous Region.Results:From 2014 to 2023, a total of 131 201 brucellosis cases were reported in Inner Mongolia Autonomous Region, with no death and an average annual incidence rate of 52.90/100 000. The lowest incidence was in 2016 (6 567 cases, 26.15/100 000), and the highest was in 2021 (21 910 cases, 91.14/100 000). All 12 cities (leagues) in the region had reported cases of brucellosis, with Tongliao City (27 012 cases), Chifeng City (15 286 cases), Hinggan League (14 859 cases), Hulunbuir (12 235 cases) and Ulanqab (11 972 cases) ranking among the top 5 cities (leagues) in terms of reported cases. Among the cases, 90 455 (68.94%) were males, with a incidence rate of 70.93/100 000, and 40 746 (31.06%) were females, with a incidence rate of 33.70/100 000. The age of onset is mainly 50 and less than 60 years old (37 610 cases, 28.67%). The occupational distribution was mainly farmers (102 091 cases, 77.81%), followed by herdsmen (13 209 cases, 10.07%).Conclusions:The incidence of human brucellosis in Inner Mongolia Autonomous Region is at a relatively high level, particularly showing an upward trend from 2016 to 2021. Cities such as Tongliao City, Chifeng City and Hinggan League have a relatively high incidence of brucellosis. Therefore, it is necessary to strengthen the monitoring of brucellosis in these areas, implement prevention and control measures, and closely monitor the changes in the trend of human brucellosis outbreaks. Farmers and herdsmen are the primary high-risk groups, and it is recommended to enhance health education and behavioral interventions for these key populations.