1.Treating acute type Ⅲ-Ⅴ acromioclavicular joint dislocation with single tunnel fixation versus tunnel-free suspension fixation of the coracoid process under shoulder arthroscopy
Yongtao ZENG ; Hongcheng ZHENG ; Nacikedaoerji ; Refati·Nijiati ; Li SHU ; Xu LIU ; Hongtao CHEN
Chinese Journal of Tissue Engineering Research 2025;29(5):1036-1042
BACKGROUND:At present,there are few reports on the postoperative efficacy of arthroscopic coracoid tunnel-free suspension fixation and coracoid single tunnel fixation in the treatment of acromioclavicular joint dislocation at home and abroad.The specific clinical efficacy of the two procedures and whether there are other risks need to be explored. OBJECTIVE:To compare the short-term postoperative clinical efficacy of arthroscopic TightRope band plate fixation with single tunnel fixation of the coracoid process and tunnel-free suspension fixation of the coracoid process in the treatment of acute type Ⅲ-Ⅴ acromioclavicular joint dislocation. METHODS:A retrospective analysis was performed in 45 patients with acromioclavicular joint dislocation who met the inclusion criteria admitted to the Sixth Affiliated Hospital of Xinjiang Medical University from June 2019 to September 2022,and were divided into coracoid single tunnel fixation group(20 cases)and coracoid tunnel-free suspension fixation group(25 cases)according to the surgical treatment plan.Operation time,incision length,blood loss,Constant-Murley score,visual analogue scale score,the American Shoulder and Elbow Surgeons(ASES)score and intraoperative and postoperative complications of the shoulder joint before operation,3 months after surgery and the last follow-up were compared between the two groups. RESULTS AND CONCLUSION:All patients successfully completed the operation,and there was no important nerve or blood vessel damage during the operation.The operation time of the coracoid tunnel-free suspension fixation group was significantly shorter than that of the coracoid tunnel-free suspension fixation group(P<0.05).There was no significant difference in intraoperative blood loss and incision length between the two groups(P>0.05).All patients were followed up for 12 to 24 months,with an average of(15.29±2.73)months.In the coracoid single tunnel fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);Constant-Murley score and ASES score were significantly increased compared with the preoperative values(P<0.05).In the coracoid tunnel-free suspension fixation group,at 3 months after operation and the final follow-up,the visual analogue scale score was significantly lower than the preoperative score(P<0.05);the Constant-Murley score and the ASES score were both significantly higher than the preoperative scores(P<0.05).At 3 months after operation,the Constant-Murley score of the coracoid tunnel-free suspension fixation group was higher than that of the coracoid single tunnel fixation group(P<0.05),while there was no significant difference in visual analogue scale and ASES scores between the two groups(P>0.05).There was also no significant difference in the visual analogue scale,Constant-Murley,and ASES scores between the two groups at the corresponding time points before surgery and at the final follow-up(P>0.05).Intraoperative and postoperative complications:In the coracoid single tunnel fixation group,there was one case of coracoid cortical rupture and fracture during the tunnel drilling during the operation,and one case of a loss of reduction at 3 months after operation,which was repositioned and fixed with hook plate transposition of the coracoacromial ligament.All patients had good acromioclavicular joint function recovery and no re-dislocation at the final follow-up.All patients in the coracoid tunnel-free suspension fixation group did not suffer from coracoid fractures,loss of reduction and other complications during surgery,postoperatively and at the last follow-up.To conclude,these two arthroscopic treatments for acute type Ⅲ-Ⅴ acromioclavicular joint dislocation have the advantages of less trauma,reliable reduction and fixation,and good recovery of shoulder joint function after operation.However,compared with the coracoid single tunnel technique,the coracoid tunnel-free suspension fixation requires shorter time,faster recovery of shoulder joint function in the short term,and avoids the establishment of bone tunnels on the coracoid process,which reduces the probability of iatrogenic fracture of the coracoid process during operation and provides a higher degree of safety.
2.Effect and mechanisms of highly active umbilical cord mesenchymal stem cells on aging spleen in elderly tree shrews
Li YE ; Chuan TIAN ; Xiaojuan ZHAO ; Mengdie CHEN ; Qianqian YE ; Qiang LI ; Zhuyin LIAO ; Ye LI ; Xiangqing ZHU ; Guangping RUAN ; Zhixu HE ; Liping SHU ; Xinghua PAN
Chinese Journal of Tissue Engineering Research 2025;29(19):4000-4010
BACKGROUND:Spleen has the functions of blood storage,hematopoiesis,and immunity.With the increase of age,the structural degeneration and functional decline of spleen lead to the impairment of immune system function,thus accelerating the aging process of the body.The treatment of spleen aging in tree shrews with highly active umbilical cord mesenchymal stem cells has not been reported. OBJECTIVE:To explore the intervention effect and mechanism of highly active umbilical cord mesenchymal stem cells on spleen aging in tree shrews. METHODS:Highly active umbilical cord mesenchymal stem cells were isolated,cultured,and obtained from the umbilical cord tissue of newborn tree shrews by caesarean section.The differentiation abilities of adipogenesis,osteogenesis,and chondrogenesis were detected by three-line differentiation kit.Cell cycle and surface markers were detected by flow cytometry.The second generation of highly active umbilical cord mesenchymal stem cells were transfected with Genechem Green Fluorescent Protein with infection complex values of 100,120,140,160,180,and 200,respectively,to screen the best transfection conditions.After transfection,the fourth generation of highly active umbilical cord mesenchymal stem cells was injected into the tail vein of tree shrews in the elderly treatment group.The young control group and the aged model group were not given special treatment.After 4 months of treatment,the spleen tissue was taken and the structure of the spleen was observed by hematoxylin-eosin staining.β-Galactosidase staining was used to detect the activity of aging-related galactosidase.Immunohistochemical staining was used to detect the expression levels of p21 and p53 proteins.Ki67 and PCNA immunofluorescence staining was used to detect cell proliferation activity.Immunofluorescence staining was used to detect the expression levels of spleen autophagy protein molecules Beclin 1 and APG5L/ATG5.Reactive oxygen species fluorescence staining was used to detect the content of reactive oxygen species in spleen tissue.CD3 immunofluorescence staining was used to detect the change of the proportion of total T lymphocytes.The secretion levels of interleukin 1β and transforming growth factor β1 in spleen were detected by enzyme linked immunosorbent assay.The distribution of highly active umbilical cord mesenchymal stem cells labeled with green fluorescent protein in spleen tissue was observed by DAPI double staining of nucleus. RESULTS AND CONCLUSION:(1)Highly active umbilical cord mesenchymal stem cells grew in a short spindle shape with fish-like growth,with a large proportion of G0/G1 phase,and had the potential to differentiate into adipogenesis,osteogenesis,and chondrogenesis.(2)Multiplicity of infection=140 and transfection for 72 hours were the best conditions for labeling tree shrews highly active umbilical cord mesenchymal stem cells with Genechem Green Fluorescent Protein.(3)Compared with the aged model group,in the aged treatment group,the spleen tissue cells of tree shrews were arranged closely,and the area of white pulp was increased(P<0.01);the boundary between red pulp and white pulp was clear;the proportion of germinal centers did not show statistically significant difference(P>0.05).The activity level of galactosidase related to spleen tissue aging was decreased(P<0.001),and the expression levels of aging protein molecules p21 and p53 were down-regulated(P<0.001).The expression levels of proliferation-related molecules Ki67 and PCNA were up-regulated(P<0.001,P<0.05);expression levels of autophagy-related molecules Beclin 1 and APG5L/ATG5 were up-regulated(P<0.001),and the content of reactive oxygen species decreased(P<0.001),and the proportion of CD3+T cells increased(P<0.05).The secretion level of interleukin 1β in the aging-related secretion phenotype decreased(P<0.001);no significant difference was found in transforming growth factor β1 level(P>0.05).Compared with the young control group,the above indexes were significantly different in the elderly treatment group(P<0.05).(4)Green fluorescent cells labeled with green fluorescent protein were observed in spleen tissue of tree shrews the elderly treatment group by frozen tissue section observation.The results show that intravenous infusion of highly active umbilical cord mesenchymal stem cells can migrate to spleen tissue,inhibit the production of reactive oxygen species,down-regulate the expression of aging-related proteins,induce autophagy,promote cell proliferation,reduce chronic inflammation,and then improve the structure and function of spleen tissue.
3.Study on quality evaluation of Mongolian medicine Sanzi powder:fingerprint,chemical pattern recognition and multi-component quantification analysis
Jun LI ; Rongjie LI ; Fengye ZHOU ; Qian ZHANG ; Wei ZHANG ; Bohan ZHANG ; Shu WANG ; Xitong ZHAO ; Jianping CHEN
China Pharmacy 2025;36(4):414-420
OBJECTIVE To establish fingerprint, chemical pattern recognition and multi-component quantification analysis of Sanzi powder, and evaluate its quality. METHODS HPLC method was adopted. The fingerprints of 15 batches of Sanzi powder were established by using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). Cluster analysis, principal component analysis and orthogonal partial least squares-discriminant analysis were also conducted. The variable importance in projection (VIP) value greater than 1 was used as the index to screen the differential markers, and the contents of the differential markers were determined by the same HPLC method. RESULTS A total of 21 common peaks in the HPLC fingerprints of 15 batches of Sanzi powder were calibrated, and the similarities of them were 0.994- 0.999; 6 common peaks were identified, including gallic acid (peak 3), garminoside (peak 10), corilagin (peak 11), chebulinic acid (peak 16), ellagic acid (peak 18), crocin Ⅰ (peak 19). According to the results of cluster analysis, YKD2024LH005,No.YKD2023LH062) principal component analysis and orthogonal partial least squares-discriminant analysis, 15 batches of samples could be clustered into two categories: S1, S5, S7, S9, S14 were clustered into one category; S2-S4, S6, S8, S10-S13, S15 were clustered into one category. VIP values of 11 differential components such as corilagin, chebulinic acid and ellagic acid were higher than 1. Among 15 batches of samples, the contents of corilagin, chebulinic acid and ellagic acid ranged 2.667-5.152, 9.506- 13.522, 0.891-1.811 mg/g. CONCLUSIONS Established HPLC fingerprint and multi-component quantification analysis of Sanzi powder are rapid and simple, and can be used for quality evaluation of Sanzi powder by combining with chemical pattern recognition. Eleven components such as corilagin, chebulinic acid and ellagic acid are differential markers affecting the quality of Sanzi powder.
4.Investigation of Component Difference of Astragali Radix Before and After Rice Stir-frying by UPLC-Q-TOF-MS/MS Combined with Chemometrics
Miaoshi YAO ; Yimeng ZHAO ; Zekun WANG ; Minglu LI ; Chenxi LIU ; Chen CHEN ; Yajun CHEN ; Yachun SHU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(4):189-197
ObjectiveA qualitative analysis method was established for the composition of Astragali Radix(AR) before and after rice stir-frying. On the basis of systematic characterization of the chemical compositions in AR and stir-fried AR with rice(ARR), the structures of their major compounds were deduced and identified, and the differential compositions between them were analyzed. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS/MS) was used to detect the samples of AR and ARR in positive and negative ion modes, respectively. The compounds were analyzed and identified through self-constructed databases, literature, and reference standards, etc. And the data were analyzed by chemometrics, in order to screen for the differential components between AR and ARR. ResultsA total of 123 compounds were identified in AR and ARR, including 41 flavonoids, 19 terpenoids, 26 organic acids, 8 amino acids, 5 nucleotides, 5 carbohydrates and 19 other compounds. Among them, there were 95 common components in both, 18 unique components in AR, and 10 unique components in ARR. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) results both showed that there were significant differences in the chemical constituents of AR before and after rice stir-frying, and a total of 26 constituents with differences in the content were screened out, including L-canavanine, L-pyroglutamic acid, L-phenylalanine, cis-caffeic acid, and malonylastragaloside Ⅰ. Among them, 19 constituents of ARR were down-regulated and 7 constituents were up-regulated by comparing with AR. ConclusionThis study clarifies that the chemical composition of AR and ARR is mainly composed of flavonoids, terpenoids, and organic acids, and analyzes the components with significant differences in content between the two in combination with chemometrics, and the differential components are dominated by amino acids, organic acids and terpenoids, which can provide reference for the subsequent quality control and material basis research.
5.Study on relationships of MS4A1 gene polymorphism with blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma
Feng SHI ; Tao LIU ; He HUANG ; Caifu FANG ; Shaoxing GUAN ; Zhang ZHANG ; Zhao WANG ; Xiaojie FANG ; Zhuojia CHEN ; Shu LIU
China Pharmacy 2025;36(13):1641-1647
OBJECTIVE To explore the effects of CD20 coding gene (MS4A1) polymorphism on the blood concentration and efficacy of rituximab in patients with non-Hodgkin’s lymphoma. METHODS A prospective observational study was conducted on 160 newly diagnosed non-Hodgkin’s lymphoma patients who received the R-CHOP regimen at the Sun Yat Sen University Cancer Center from January 2016 to December 2020, with a minimum follow-up period of approximately 5 years. The blood concentration of rituximab was detected by enzyme-linked immunosorbent assay. MS4A1 tagSNPs were selected by Haploview4.2 software, including rs1051461, rs17155034, rs4939364, and rs10501385. The genotype of MS4A1 was detected by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Univariate linear regression analysis was employed to examine the correlation between various factors(demographic, clinical, and genotypic variables) in patients and the steady-state trough concentration of rituximab during the first course of treatment, followed by multivariate linear regression analysis. Kaplan-Meier curves were drawn to evaluate progression-free survival (PFS) and overall survival (OS). Using MS4A1 genotype and tumor stage as independent variables, Cox regression model was employed to evaluate the factors influencing patient prognosis. RESULTS The blood concentration of rituximab in MS4A1 rs10501385 CC carriers was 15.20 μg/mL,which was significantly lower than 21.95 μg/mL in AA+AC carriers (P<0.05). The multivariate linear regression model incorporating tumor stage and MS4A1 rs10501385 polymorphism explained 7.3% of the interindividual variability in rituximab concentrations. Compared with MS4A1 rs1051461 CC carriers, CT+TT carriers had significantly prolonged PFS and OS (P<0.05). The Cox proportional hazards regression model showed that the MS4A1 rs1051461 CC genotype (HR=4.406, 95%CI:1.743-11.137, P<0.05) and tumor Ⅲ&Ⅳ (HR=3.233, 95%CI: 1.413-7.399, P<0.05) were independent risk factors for PFS. CONCLUSIONS The tumor staging and MS4A1 rs10501385 polymorphism are key influencing factors for blood concentration of rituximab, and MS4A1 rs1051461 polymorphism significantly affects PFS in non-Hodgkin’s lymphoma patients.
6.Establishment of a standardized management model for postoperative anti-osteoporosis medication in patients with brittle fractures
Hao LIU ; Yinglin YANG ; Le CAI ; Shu LI ; Man ZHU ; Mengli CHEN
China Pharmacy 2025;36(15):1926-1930
OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists, and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024,595 post-brittle fracture surgery patients were enrolled. Using the PDCA (plan-do-check-act) cycle,resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before, during and after treatment, a medication treatment pathway was developed, thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform (under the National Clinical Research Center for Orthopedics and Sports Rehabilitation), a dedicated data module was constructed, providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis (from 9% before intervention to 81%) and proportion of drug treatment (from 4% to 75%).The proportions of bone density and bone metabolism testing also rose markedly,positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis, ensures rational medication use in osteoporosis patients, and demonstrates significant potential for widespread adoption and application.
7.Research progress on the pathogenesis of chronic obstructive pulmonary disease complicated with lung cancer
Anying LI ; Zhiwei LI ; Dianhan SUN ; Yong CHEN ; Jun WU ; Yusheng SHU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(06):855-862
Chronic obstructive pulmonary disease (COPD), which predominantly affects middle-aged and elderly individuals, is associated with a significantly reduced quality of life and often triggers various other pulmonary conditions. Lung cancer, as one of the most prevalent and deadly pulmonary malignancies worldwide, poses a severe threat to global public health. The risk of developing lung cancer is markedly higher in COPD patients compared to the general population, indicating numerous associations between the two conditions that warrant in-depth investigation. Although a substantial body of research has explored the relationship between COPD and lung cancer, studies focusing on the molecular mechanisms underlying their connection remain limited. This article reviews the latest research progress on the mechanisms of COPD complicated by lung cancer from four perspectives: the role of chronic pulmonary inflammation, programmed cell death, genetic and molecular interactions, and dysbiosis of the pulmonary microbiome. The aim of this article is to provide new insights and references for the prevention and therapeutic strategies of COPD complicated with lung cancer.
8.The Application of Spatial Resolved Metabolomics in Neurodegenerative Diseases
Lu-Tao XU ; Qian LI ; Shu-Lei HAN ; Huan CHEN ; Hong-Wei HOU ; Qing-Yuan HU
Progress in Biochemistry and Biophysics 2025;52(9):2346-2359
The pathogenesis of neurodegenerative diseases (NDDs) is fundamentally linked to complex and profound alterations in metabolic networks within the brain, which exhibit marked spatial heterogeneity. While conventional bulk metabolomics is powerful for detecting global metabolic shifts, it inherently lacks spatial resolution. This methodological limitation hampers the ability to interrogate critical metabolic dysregulation within discrete anatomical brain regions and specific cellular microenvironments, thereby constraining a deeper understanding of the core pathological mechanisms that initiate and drive NDDs. To address this critical gap, spatial metabolomics, with mass spectrometry imaging (MSI) at its core, has emerged as a transformative approach. It uniquely overcomes the limitations of bulk methods by enabling high-resolution, simultaneous detection and precise localization of hundreds to thousands of endogenous molecules—including primary metabolites, complex lipids, neurotransmitters, neuropeptides, and essential metal ions—directly in situ from tissue sections. This powerful capability offers an unprecedented spatial perspective for investigating the intricate and heterogeneous chemical landscape of NDD pathology, opening new avenues for discovery. Accordingly, this review provides a comprehensive overview of the field, beginning with a discussion of the technical features, optimal application scenarios, and current limitations of major MSI platforms. These include the widely adopted matrix-assisted laser desorption/ionization (MALDI)-MSI, the ultra-high-resolution technique of secondary ion mass spectrometry (SIMS)-MSI, and the ambient ionization method of desorption electrospray ionization (DESI)-MSI, along with other emerging technologies. We then highlight the pivotal applications of spatial metabolomics in NDD research, particularly its role in elucidating the profound chemical heterogeneity within distinct pathological microenvironments. These applications include mapping unique molecular signatures around amyloid β‑protein (Aβ) plaques, uncovering the metabolic consequences of neurofibrillary tangles composed of hyperphosphorylated tau protein, and characterizing the lipid and metabolite composition of Lewy bodies. Moreover, we examine how spatial metabolomics contributes to constructing detailed metabolic vulnerability maps across the brain, shedding light on the biochemical factors that render certain neuronal populations and anatomical regions selectively susceptible to degeneration while others remain resilient. Looking beyond current applications, we explore the immense potential of integrating spatial metabolomics with other advanced research methodologies. This includes its combination with three-dimensional brain organoid models to recapitulate disease-relevant metabolic processes, its linkage with multi-organ axis studies to investigate how systemic metabolic health influences neurodegeneration, and its convergence with single-cell and subcellular analyses to achieve unprecedented molecular resolution. In conclusion, this review not only summarizes the current state and critical role of spatial metabolomics in NDD research but also offers a forward-looking perspective on its transformative potential. We envision its continued impact in advancing our fundamental understanding of NDDs and accelerating translation into clinical practice—from the discovery of novel biomarkers for early diagnosis to the development of high-throughput drug screening platforms and the realization of precision medicine for individuals affected by these devastating disorders.
9.Influence of occupational hazard factors on incidence of hypertension in calcium carbide plant: Historical cohort study
Meng LIU ; Wei ZHANG ; Qi ZHUANG ; Xingyu PENG ; Jinling LIU ; Tiantian CHEN ; Hongmei GU ; Shu GUO
Journal of Environmental and Occupational Medicine 2025;42(5):565-570
Background The high work intensity and possible subsequently increased susceptibility to occupational hazards of calcium carbide plants may lead to hypertension in workers, but there are few studies on the relationship between occupational hazard exposure and hypertension in workers involving the production process of calcium carbide. Objective To explore the influence of occupational hazards on the incidence of hypertension in calcium carbide plants. Methods Using historical cohort design, the employees of a calcium carbide factory in the western part of Inner Mongolia Autonomous Region were selected as research subjects. According to the pre-determined inclusion and exclusion criteria, the study population comprised an exposure group of 377 employees (including furnace workers, inspection workers, and maintenance workers) exposed to dust, noise & carbon monoxide, and a control group of 388 employees (including central control workers, electricians, and administrative personnel) without above-mentioned exposure. The total sample size was 765 participants. The follow-up period was from April 2011 to October 2022, and the study endpoint was defined as the conclusion of the follow-up period or diagnosed hypertension in annual occupational health examination. Information on general demographic characteristics, living habits, and work status was collected from all study subjects. Cox proportional hazards regression model was used to analyze the association between occupational hazard exposure and the risk of hypertension among the calcium carbide plant employees. Results The average age, mean systolic and diastolic blood pressure, proportion of males, smoking rate, and alcohol consumption rate in the exposure group were higher than those in the control group (P<0.05). Compared to baseline, both systolic and diastolic blood pressure levels increased in the exposure group and the control group at the end of the follow-up (P<0.05). At the end of the follow-up, the average differences between systolic/ diastolic blood pressure and baseline values in the exposure group were higher than those in the control group (P<0.05). During the follow-up period, a total of 223 cases of hypertension occurred, with a total follow-up of
10.Role of 5-aminosalicylic acid in ulcerative colitis management in 8 Asian territories: a physician survey
Julajak LIMSRIVILAI ; Allen Yu-hung LAI ; Silvia T. H. LI ; Murdani ABDULLAH ; Raja Affendi Raja ALI ; Satimai ANIWAN ; Hoang Huu BUI ; Jen-Wei CHOU ; Ida Normiha HILMI ; Wee Chian LIM ; Jose SOLLANO ; Michelle Mui Hian TEO ; Shu-Chen WEI ; Wai Keung LEUNG
Intestinal Research 2025;23(2):117-128
Clinical guidelines typically endorse conventional therapies such as 5-aminosalicylic acid (5-ASA) as the mainstay of ulcerative colitis management. However, the degree of adoption and application of guideline recommendations by physicians within Asia remains unclear. This study aims to understand the prescribing patterns of 5-ASA and implementation of current guideline recommendations across Asian clinical practice. A physician survey was conducted among inflammatory bowel disease specialists in 8 Asian territories to understand practices and preferences in ulcerative colitis management, focusing on the use of 5-ASA and concordance with guideline recommendations. Survey findings were validated by country experts in diverse healthcare settings. Subgroup analyses stratified data by income levels and treatment reimbursement status. Ninety-eight valid responses were received from inflammatory bowel disease specialists or gastroenterologists among 8 economic entities. Significant differences were found in clinical practices and treatment preferences for ulcerative colitis management among different income-level and government-subsidy groups. Survey results are summarized in 8 findings that illustrate trends in 5-ASA use and guideline implementation across Asian territories. This study emphasizes socioeconomic factors that impact the adoption of guideline recommendations in real-world practice. Our findings indicate an eclectic approach to guideline implementation across Asia, based on resource availability and feasibility of treatment goals.

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