1.Traditional Chinese Medicine Intervention in Parkinson's Disease Based on Keap1/Nrf2/ARE Signaling Pathway: A Review
Liuping YUE ; Yongkang SUN ; Fangbiao XU ; Yanbo SONG ; Yijun WU ; Huan YU ; Xinzhi WANG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):307-317
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder primarily characterized by motor dysfunction. The main pathological features include the loss of dopaminergic neurons in the substantia nigra, abnormal aggregation of alpha-Synuclein (α-Syn), and the formation of Lewy bodies. However, the exact mechanisms remain unclear. In recent years, the PD incidence has gradually increased, while current treatment methods are limited to symptom alleviation, incapable of halting disease progression, and prone to adverse effects, thus making it urgent to search for medicines effective for PD. Modern research indicates that the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor E2 related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway is closely related to oxidative stress, neuroinflammation, apoptosis, ferroptosis, and mitochondrial dysfunction, playing a crucial role in the pathophysiological development of PD. A large number of studies have further confirmed that traditional Chinese medicine (TCM) can regulate diseases through a holistic view of Syndrome differentiation and microscopic molecular pathways. With unique advantages, such as multiple targets, multiple pathways, and fewer adverse reactions, TCM provides a new strategy for PD treatment. This article elucidates the mechanism of the Keap1/Nrf2/ARE signaling pathway in the occurrence and development of PD, while summarizing the latest research on PD intervention by TCM monomers, active ingredients, and compounds, as well as acupuncture via the precise targeted regulation of the Keap1/Nrf2/ARE pathway, aiming to provide a reference for clinical medicine development to prevent and treat PD.
2.Skeleton Binding Protein 1 of Plasmodium berghei Influences Deformability and Cytoskeletal Ultrastructure of Infected Erythrocyte
Xin-Yue GUO ; Huan-Qi ZHAO ; Yan-Xuan ZHONG ; Ru-Meng JIANG ; Yao-Xian LI ; Lei-Ting PAN ; Qian WANG ; Xiao-Yu SHI
Progress in Biochemistry and Biophysics 2026;53(4):1015-1027
ObjectiveThe malaria parasites remodel the host erythrocyte structure by exporting parasite proteins that interact with the membrane skeleton proteins of red blood cells (RBCs), facilitating their intracellular survival and pathogenicity. Skeleton-binding protein 1 (SBP1) is a conserved exported protein across Plasmodium species. In Plasmodium falciparum, SBP1 has been reported to interact with erythrocyte membrane skeleton proteins 4.1R and spectrin, while its contribution to erythrocyte remodeling and parasite virulence in Plasmodium berghei (Pb) remains unclear. This study aims to determine whether PbSBP1 associates with the host cytoskeletal protein 4.1R and to investigate its role in the remodeling of host RBCs and the pathogenicity of Plasmodium berghei. MethodsIn Plasmodium berghei, the relationship between PbSBP1 and the erythrocyte cytoskeletal protein 4.1R was examined using co-immunoprecipitation. A Pbsbp1 gene knockout mutant of Plasmodium berghei (Pbsbp1∆) was generated based on the principle of double crossover homologous recombination. The deformability of erythrocytes infected with Pbsbp1∆ parasites was assessed using microfluidic methods. Microchannels with an array of cylindrical pillars were used to detect modifications in infected RBC deformability. The infected RBCs were squashed between the rows and recovered between the columns and the transit velocity (μm/s) of infected RBCs travelling through the microchannel was recorded. The component of the erythrocyte membrane skeleton junctional complex, tropomodulin (TMOD), was fluorescently labeled, and the cytoskeletal network of infected erythrocytes was imaged using super-resolution stochastic optical reconstruction microscopy (STORM) to analyze ultrastructural changes in the cytoskeleton of wild-type (WT) and Pbsbp1∆-infected erythrocytes. Actin-based junctional complexes were displayed as individual clusters by the labeled TMOD in the STORM images, and the cluster densities and distances between adjacent clusters of infected RBCs were calculated. Additionally, rodent malaria models (BALB/c mice) and experimental cerebral malaria models (C57BL/6 mice) were employed to monitor the growth of Pbsbp1∆ and WT parasites during the intraerythrocytic stage and their capacity to induce cerebral malaria in mice. ResultsPbSBP1 may participate in the remodeling of infected erythrocytes through direct or indirect interaction with the erythrocyte cytoskeletal protein 4.1R. Microfluidic assays revealed that the deformability of erythrocytes infected with Pbsbp1∆ parasites was significantly enhanced compared to those infected with WT parasites. STORM imaging further demonstrated that the ultrastructure of the erythrocyte cytoskeleton in Pbsbp1∆-infected cells was altered relative to that in WT-infected erythrocytes. The distances between nearest neighbors of clusters had a tendency to increase while the cluster densities were decreased in Pbsbp1∆-infected RBCs compared to WT-infected RBCs. Subsequent phenotypic analysis indicated that the growth rate of Pbsbp1∆ parasites during the intraerythrocytic stage was significantly slower than that of WT parasites, and their ability to induce cerebral malaria in mice was also attenuated. These findings suggest that PbSBP1 is involved in the remodeling of the erythrocyte membrane skeleton, likely through its direct or indirect interaction with protein 4.1R, thereby regulating the deformability of infected erythrocytes and influencing the pathogenicity of the blood-stage parasites. ConclusionThis study establishes a role for PbSBP1 in host erythrocyte remodeling and parasite virulence, providing new research strategies for the prevention and treatment of malaria.
3.Proteomic Preparation Techniques for Formalin-Fixed Paraffin-Embedded Tissue Samples
Ao LU ; Bo MENG ; Jia-Wei ZHAO ; Huan-Yue LIAO ; Zi-Hong YE ; Xiang FANG ; Yang ZHAO
Chinese Journal of Analytical Chemistry 2025;53(1):84-93,中插4-中插8
Twelve pre-processing protocols for formalin-fixed paraffin-embedded(FFPE)tissue samples were developed by orthogonal experimental design,incorporating different dewaxing buffers(Triton X-100 and xylene),lysis buffers(TFE and RapiGest),and enzyme digestion methods(iST,SP3,and FASP)to explore the optimal experimental conditions.These protocols were assessed based on protein and peptide identification depth,identification stability,and quantitative levels of protein abundance.The results indicated that Triton X-100 and xylene minimally impacted proteomics identification,whereas the TFE lysis buffer and iST digestion method significantly enhanced the proteomics analysis of FFPE samples.Considering the potential toxicity of xylene,the TTI protocol based on Triton X-100,TFE,and iST was determined to be the optimal choice.This protocol exhibited the best repeatability and stability,and a higher number of proteins associated with significant biological functions were identified.In conclusion,the established TTI protocol offered an efficient and comprehensive approach for proteomic analysis of FFPE samples,significantly enhancing the repeatability and stability of protein identification.
4.Effects and mechanism of astragalus mongholicus extract on lung injury in rats with rheumatoid arthritis induced interstitial lung disease
Yue Zhao ; Jinliang Yang ; Huan Luo ; Wenxiu Xi ; Junlu Wang ; Xuejun Zheng
Acta Universitatis Medicinalis Anhui 2025;60(7):1173-1179
Objective :
To investigate the effects of astragalus mongholicus extract ( AME) on lung injury and the myeloid differentiation factor 88 ( MyD88 ) / Toll-like receptor 4 ( TLR4 ) / nuclear factor kappa B ( NF-κB) p65 pathway in rheumatoid arthritis induced interstitial lung disease (RA-ILD) rats.
Methods :
SD rats were randomly divided into a control group,RA-ILD group,low-dose AME group (5 g / L) ,high-dose AME group ( 10 g / L) ,and high-dose AME + lipopolysaccharide (LPS) group ( 10 g / L AME + 1 mg / L TLR4 activator LPS) .Except for the control group,rats in all other groups were injected with bovine type Ⅱ collagen,Freund ’s complete adjuvant, and bleomycin to establish the RA-ILD model.The arthritis index and lung tissue wet-dry weight ratio of rats were tested.ELISA was applied to detect the levels of inflammatory factors interleukin (IL) -1 β , IL-6 and tumor necrosis factor-α ( TNF-α) in bronchoalveolar lavage fluid. Hematoxylin eosin staining was used to observe pathological changes of rat knee joint tissue and lung tissue.Western blot was applied to detect the expression of autophagy fac- tors Beclin 1,microtubule-associated protein 1A /1B-light chain 3 (LC3) Ⅱ / Ⅰ , and MyD88 /TLR4 /NF-κB p65 pathway related proteins in lung tissue.
Results :
Compared with control group,knee joint tissue and lung tissue of rats in RA-ILD group were damaged,the arthritis index,lung tissue wet-dry weight ratio,levels of IL-1 β , IL-6, and TNF-α , the expression levels of MyD88 and TLR4 proteins ,and p-NF-κB p65 /NF-κB p65 ratio increased (P<0. 01) ,the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins decreased (P<0. 01) .Compared with RA-ILD group,the low-dose and high-dose AME groups showed reduced tissue damage in rats,the arthritis index,lung tis- sue wet-dry weight ratio,levels of IL-1 β , IL-6,and TNF-α , the expression levels of MyD88 and TLR4 proteins, and p-NF-κB p65 /NF-κB p65 ratio showed a dose-dependent decrease (P<0. 05 or P<0. 01) ,the expression of Beclin 1 and LC3 Ⅱ / Ⅰ proteins showed a dose-dependent increase (P<0. 05 or P<0. 01) .Compared with high- dose AME group,the tissue damage of rats in the high-dose AME + LPS group was worsened,the arthritis index, lung tissue wet-dry weight ratio,levels of IL-1 β , IL-6,and TNF-α , the expression levels of MyD88 and TLR4 pro- teins,and p-NF-κB p65 /NF-κB p65 ratio were higher (P<0. 01) ,the expression of Beclin 1 and LC3 Ⅱ / Ⅰ pro- teins was lower (P <0. 01 ) .
Conclusion
AME inhibits the MyD88 /TLR4 /NF-κB p65 pathway and alleviates lung injury in RA-ILD rats.
5.Application of Recombinant Collagen in Biomedicine
Huan HU ; Hong ZHANG ; Jian WANG ; Li-Wen WANG ; Qian LIU ; Ning-Wen CHENG ; Xin-Yue ZHANG ; Yun-Lan LI
Progress in Biochemistry and Biophysics 2025;52(2):395-416
Collagen is a major structural protein in the matrix of animal cells and the most widely distributed and abundant functional protein in mammals. Collagen’s good biocompatibility, biodegradability and biological activity make it a very valuable biomaterial. According to the source of collagen, it can be broadly categorized into two types: one is animal collagen; the other is recombinant collagen. Animal collagen is mainly extracted and purified from animal connective tissues by chemical methods, such as acid, alkali and enzyme methods, etc. Recombinant collagen refers to collagen produced by gene splicing technology, where the amino acid sequence is first designed and improved according to one’s own needs, and the gene sequence of improved recombinant collagen is highly consistent with that of human beings, and then the designed gene sequence is cloned into the appropriate vector, and then transferred to the appropriate expression vector. The designed gene sequence is cloned into a suitable vector, and then transferred to a suitable expression system for full expression, and finally the target protein is obtained by extraction and purification technology. Recombinant collagen has excellent histocompatibility and water solubility, can be directly absorbed by the human body and participate in the construction of collagen, remodeling of the extracellular matrix, cell growth, wound healing and site filling, etc., which has demonstrated significant effects, and has become the focus of the development of modern biomedical materials. This paper firstly elaborates the structure, type, and tissue distribution of human collagen, as well as the associated genetic diseases of different types of collagen, then introduces the specific process of producing animal source collagen and recombinant collagen, explains the advantages of recombinant collagen production method, and then introduces the various systems of expressing recombinant collagen, as well as their advantages and disadvantages, and finally briefly introduces the application of animal collagen, focusing on the use of animal collagen in the development of biopharmaceutical materials. In terms of application, it focuses on the use of animal disease models exploring the application effects of recombinant collagen in wound hemostasis, wound repair, corneal therapy, female pelvic floor dysfunction (FPFD), vaginal atrophy (VA) and vaginal dryness, thin endometritis (TE), chronic endometritis (CE), bone tissue regeneration in vivo, cardiovascular diseases, breast cancer (BC) and anti-aging. The mechanism of action of recombinant collagen in the treatment of FPFD and CE was introduced, and the clinical application and curative effect of recombinant collagen in skin burn, skin wound, dermatitis, acne and menopausal urogenital syndrome (GSM) were summarized. From the exploratory studies and clinical applications, it is evident that recombinant collagen has demonstrated surprising effects in the treatment of all types of diseases, such as reducing inflammation, promoting cell proliferation, migration and adhesion, increasing collagen deposition, and remodeling the extracellular matrix. At the end of the review, the challenges faced by recombinant collagen are summarized: to develop new recombinant collagen types and dosage forms, to explore the mechanism of action of recombinant collagen, and to provide an outlook for the future development and application of recombinant collagen.
6.Processing technology of calcined Magnetitum based on concept of QbD and its XRD characteristic spectra.
De-Wen ZENG ; Jing-Wei ZHOU ; Tian-Xing HE ; Yu-Mei CHEN ; Huan-Huan XU ; Jian FENG ; Yue YANG ; Xin CHEN ; Jia-Liang ZOU ; Lin CHEN ; Hong-Ping CHEN ; Shi-Lin CHEN ; Yuan HU ; You-Ping LIU
China Journal of Chinese Materia Medica 2025;50(9):2391-2403
Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods*
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Drugs, Chinese Herbal/chemistry*
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Quality Control
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Particle Size
7.Coptidis Rhizoma-Scutellariae Radix alleviates CpG1826-induced cytokine storm secondary lung injury in mice by inhibiting mPTP/NLRP3 pyroptosis pathway.
Qing-Rui ZHONG ; Hong-Kai HUANG ; Yue-Jia LAN ; Huan WANG ; Yong ZENG ; Jia-Si WU
China Journal of Chinese Materia Medica 2025;50(15):4141-4152
This study aims to investigate the therapeutic effects of the Coptidis Rhizoma-Scutellariae Radix on cytokine storm secondary lung injury(CSSLI) induced by CpG1826 in mice, and to elucidate the potential molecular mechanisms by which its major active components, i.e., coptisine and wogonin, alleviate CSSLI by inhibiting the mitochondrial permeability transition pore(mPTP)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome pyroptosis pathway. In vivo, a mouse model of CSSLI was established by CpG1826 induction. Pulmonary edema was assessed by lung wet-to-dry weight ratio(W/D), lung injury was evaluated by hematoxylin-eosin(HE) staining, and ultrastructural changes in lung tissue were observed by transmission electron microscopy(TEM). The levels of interleukin(IL)-1β, high mobility group box 1 protein(HMGB1), IL-18, and IL-1α in bronchoalveolar lavage fluid were measured by enzyme-linked immunosorbent assay(ELISA). The results showed that the decoction of the Coptidis Rhizoma-Scutellariae Radix significantly reduced pulmonary edema, alleviated lung injury, and decreased the concentrations of related cytokines in BALF more effectively than either single herb alone, thereby improving CSSLI. In vitro, a CpG1826-induced CSSLI model was established in mouse alveolar macrophage MH-S cells. Calcein-AM quenching was used to screen for the most effective monomer components from the herb pair in inhibiting mPTP opening. Coptisine(5, 10, 20 μmol·L~(-1)) and wogonin(10, 20, 40 μmol·L~(-1)) markedly inhibited mPTP opening, with optimal effects and a clear dose-dependent pattern. These components suppressed mPTP opening, thereby reducing the release of mitochondrial DNA(mtDNA) and the accumulation of reactive oxygen species(ROS), effectively reversing the CpG1826-induced decrease in mitochondrial membrane potential(MMP). Further studies revealed that both coptisine and wogonin inhibited pyroptosis and downregulated the expression of key proteins in the NLRP3/Caspase-1/gasdermin D(GSDMD) pathway. In conclusion, the Coptidis Rhizoma-Scutellariae Radix improves CpG1826-induced CSSLI in mice, and this effect is associated with the inhibition of the mPTP/NLRP3 pyroptosis pathway, providing scientific evidence for its clinical application and further development.
Animals
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Mice
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Drugs, Chinese Herbal/administration & dosage*
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Pyroptosis/drug effects*
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NLR Family, Pyrin Domain-Containing 3 Protein/immunology*
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Male
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Lung Injury/immunology*
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Cytokines/immunology*
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Scutellaria baicalensis/chemistry*
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Oligodeoxyribonucleotides/adverse effects*
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Mice, Inbred C57BL
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Coptis chinensis
8.Research on the relationship between resting-state spontaneous electroencephalography and task-evoked electroencephalography.
Huan HE ; Xiaolin XIAO ; Jin YUE ; Minpeng XU ; Dong MING
Journal of Biomedical Engineering 2025;42(3):620-627
In recent years, it has become a new direction in the field of neuroscience to explore the mode characteristics, functional significance and interaction mechanism of resting spontaneous electroencephalography (EEG) and task-evoked EEG. This paper introduced the basic characteristics of spontaneous EEG and task-evoked EEG, and summarized the core role of spontaneous EEG in shaping the adaptability of the nervous system. It focused on how the spontaneous EEG interacted with the task-evoked EEG in the process of task processing, and emphasized that the spontaneous EEG could significantly affect the performance of tasks such as perception, cognition and movement by regulating neural activities and predicting external stimuli. These studies provide an important theoretical basis for in-depth understanding of the principle and mechanism of brain information processing in resting and task states, and point out the direction for further exploring the complex relationship between them in the future.
Humans
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Electroencephalography/methods*
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Brain/physiology*
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Rest/physiology*
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Cognition/physiology*
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Evoked Potentials/physiology*
;
Task Performance and Analysis
9.Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study.
Yue JIANG ; Claire Chenwen ZHONG ; Betty Huan WANG ; Shan-Shan XU ; Fai Fai HO ; Ming Hong KWONG ; Leonard HO ; Joson Hao-Shen ZHOU ; K C LAM ; Jian-Ping LIU ; Bao-Ting ZHANG ; Vincent Chi Ho CHUNG
Journal of Integrative Medicine 2025;23(5):492-501
OBJECTIVE:
This cross-sectional study assessed the methodological quality of systematic reviews (SRs) of Chinese herbal medicine (CHM) published in Chinese between Jan 2021 and Sep 2022.
METHODS:
Chinese language CHM SRs were identified through literature searches across 3 international and 4 Chinese databases. Methodological quality was appraised using A MeaSurement Tool to Assess systematic Reviews 2. Logistic regressions were used to explore associations between bibliographical characteristics and quality.
RESULTS:
Analyses of methodological quality found that among the 213 sampled SRs, 69.5% were of critically low quality, 30.5% were of low quality, and none achieved high or moderate quality. Common shortcomings included the failure to identify the studies excluded from the analysis, failure to disclose funding sources, and limited evaluation of the potential impact of bias on conclusions. Logistic regressions revealed that SRs led by corresponding authors affiliated with universities or academic institutions tended to be of lower quality than SRs led by authors affiliated with hospitals or clinical facilities.
CONCLUSION
Recent Chinese language CHM SRs exhibited limited methodological quality, making them unlikely to support the development of clinical practice guidelines. Urgent initiatives are needed to enhance training for researchers, peer-reviewers and editors involved in the preparation and publication of SRs. Adoption of Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines in Chinese language journals is crucial to improve the relevance of SRs for Chinese medicine development. Addressing deficiencies in methodology and reporting is essential for promoting evidence-based practices and informed clinical decisions in Chinese medicine. Please cite this article as: Jiang Y, Zhong CC, Wang BH, Xu SS, Ho FF, Kwong MH, Ho L, Zhou JHS, Lam KC, Liu JP, Zhang BT, Chung VCH. Methodological quality of systematic reviews on orally administered Chinese herbal medicine published in Chinese between 2021 and 2022: A cross-sectional study. J Integr Med. 2025; 23(5):492-501.
Cross-Sectional Studies
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Drugs, Chinese Herbal/administration & dosage*
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Systematic Reviews as Topic/standards*
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Humans
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China
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Administration, Oral
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Medicine, Chinese Traditional
10.HIV Pretreatment Drug Resistance and Transmission Clusters among Newly Diagnosed Patients in the China-Myanmar Border Region, 2020-2023.
Huan LIU ; Yue Cheng YANG ; Xing DUAN ; Yi Chen JIN ; Yan Fen CAO ; Yi FENG ; Chang CAI ; He He ZHAO ; Hou Lin TANG
Biomedical and Environmental Sciences 2025;38(7):840-847
OBJECTIVE:
This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China.
METHODS:
Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site.
RESULTS:
Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL.
CONCLUSION
The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans
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HIV Infections/virology*
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China/epidemiology*
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Drug Resistance, Viral
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Male
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Adult
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Female
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Middle Aged
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HIV-1/genetics*
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Anti-HIV Agents/therapeutic use*
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Myanmar/epidemiology*
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Young Adult
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Prevalence
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Adolescent
;
Mutation


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