1.Clinical Advantages of Traditional Chinese Medicine in Treatment of Childhood Simple Obesity: Insights from Expert Consensus
Qi ZHANG ; Yingke LIU ; Xiaoxiao ZHANG ; Guichen NI ; Heyin XIAO ; Junhong WANG ; Liqun WU ; Zhanfeng YAN ; Kundi WANG ; Jiajia CHEN ; Hong ZHENG ; Xinying GAO ; Liya WEI ; Qiang HE ; Qian ZHAO ; Huimin SU ; Zhaolan LIU ; Dafeng LONG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(6):238-245
Childhood simple obesity has become a significant public health issue in China. Modern medicine primarily relies on lifestyle interventions and often suffers from poor long-term compliance, while pharmacological options are limited and associated with potential adverse effects. Traditional Chinese Medicine (TCM) has a long history in the prevention and management of this condition, demonstrating eight distinct advantages, including systematic theoretical foundation, diversified therapeutic approaches, definite therapeutic efficacy, high safety profile, good patient compliance, comprehensive intervention strategies, emphasis on prevention, and stepwise treatment protocols. Additionally, TCM is characterized by six distinctive features: the use of natural medicinal substances, non-invasive external therapies, integration of medicinal dietetics, simple exercise regimens, precise syndrome differentiation, and diverse dosage forms. By combining internal and external treatments, TCM facilitates individualized regimen adjustment and holistic regulation, demonstrating remarkable effects in improving obesity-related metabolic indicators, regulating constitutional imbalance, and promoting healthy behaviors. However, challenges remain, such as inconsistent operational standards, insufficient high-quality clinical evidence, and a gap between basic research and clinical application. Future efforts should focus on accelerating the standardization of TCM diagnosis and treatment, conducting multicenter randomized controlled trials, and fostering interdisciplinary integration, so as to enhance the scientific validity and international recognition of TCM in the prevention and treatment of childhood obesity.
2.MCC950 Targeted Inhibition of TXNIP-NLRP3 Axis-mediated Podocyte Pyroptosis in Diabetic Nephropathy
Hong ZHENG ; Zhong-Cheng MO ; Hang LIU ; Xi-Zhang PAN ; Bing WEI
Progress in Biochemistry and Biophysics 2026;53(2):418-430
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.
3.MCC950 Targeted Inhibition of TXNIP-NLRP3 Axis-mediated Podocyte Pyroptosis in Diabetic Nephropathy
Hong ZHENG ; Zhong-Cheng MO ; Hang LIU ; Xi-Zhang PAN ; Bing WEI
Progress in Biochemistry and Biophysics 2026;53(2):418-430
Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) globally, representing a major global health burden with limited disease-modifying therapies. Podocyte injury serves as the core pathological hallmark of DN, and conventional treatments targeting metabolic disorders or hemodynamic abnormalities fail to reverse the progressive decline of renal function. Accumulating evidence over the past decade has established that high glucose-induced podocyte pyroptosis—a pro-inflammatory form of programmed cell death—is a key driving force in DN progression. Its core molecular mechanism hinges on the activation of the TXNIP-NLRP3 inflammasome axis. Under sustained hyperglycemic conditions, excessive reactive oxygen species (ROS) are generated via pathways including the polyol pathway, advanced glycation end products (AGEs) accumulation, and mitochondrial dysfunction. Concurrently, methylglyoxal (a glucose metabolite) mediates post-translational modification of thioredoxin-interacting protein (TXNIP). These events collectively trigger the dissociation of TXNIP from thioredoxin (TRX), a redox-regulating protein. The free TXNIP then translocates to the mitochondria, where it binds to The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) and promotes inflammasome assembly. This assembly activates cysteine-aspartic acid protease 1 (caspase-1), which cleaves Gasdermin D (GSDMD) to generate its N-terminal fragment (GSDMD-NT). GSDMD-NT oligomerizes to form membrane pores, leading to podocyte swelling, rupture, and the release of pro-inflammatory cytokines interleukin-1β (IL-1β) and interleukin-18 (IL-18). These cytokines amplify local inflammatory responses, induce mesangial cell proliferation, and accelerate extracellular matrix deposition, ultimately exacerbating glomerulosclerosis. MCC950, a highly selective NLRP3 inhibitor, exerts its therapeutic effects through a multi-layered mechanism: it binds to the NACHT domain (NAIP, CIITA, HET-E and TP1 domain) of NLRP3 with nanomolar affinity, forming hydrogen bonds with key residues (Lys-42 and Asp-166) within the ATP-hydrolysis pocket to block ATP hydrolysis, thereby locking NLRP3 in an inactive conformational state. Additionally, MCC950 interferes with the protein-protein interaction between TXNIP and NLRP3 and regulates mitochondrial homeostasis to reduce ROS production. Preclinical studies have demonstrated that MCC950 dose-dependently reduces proteinuria, restores the expression of podocyte-specific markers (nephrin and Wilms tumor 1 protein, WT1), and alleviates podocyte foot process fusion and glomerulosclerosis in both streptozotocin (STZ)-induced type 1 diabetic models (characterized by absolute insulin deficiency) and db/db type 2 diabetic models (driven by insulin resistance). However, discrepancies in therapeutic outcomes exist across different models—some studies report exacerbated renal inflammation and fibrosis in STZ-induced models—which may stem from differences in disease pathogenesis, intervention timing (early vs. mid-stage disease), and dosing duration. Despite its promising preclinical efficacy, MCC950 faces significant translational challenges, including low oral bioavailability, insufficient podocyte targeting, potential hepatotoxicity, and drug-drug interactions with statins (commonly prescribed to diabetic patients for cardiovascular risk management). Furthermore, off-target effects such as the inhibition of carbonic anhydrase 2 have been identified, raising concerns about its safety profile. Nevertheless, its unique mechanism of action—directly blocking podocyte pyroptosis by targeting the TXNIP-NLRP3 axis—endows it with substantial translational value. In the future, strategies to overcome these barriers are expected to advance its clinical application: targeted delivery via nanocarriers (e.g., PLGA-PEG nanoparticles or nephrin antibody-conjugated systems) to enhance renal accumulation and podocyte specificity; precise patient stratification based on biomarkers such as serum IL-18 and renal TXNIP/NLRP3 expression to identify “inflammatory-phenotype” DN patients most likely to benefit; and combination therapy with sodium-glucose cotransporter 2 (SGLT2) inhibitors—whose metabolic benefits synergize with MCC950’s anti-inflammatory effects. These approaches hold great potential to break through clinical translation bottlenecks, offering a novel, precise anti-inflammatory treatment option for DN and addressing an unmet clinical need for therapies targeting the inflammatory underpinnings of the disease.
4.Safety and efficacy of immunoadsorption therapy for rheumatoid arthritis:a network meta-analysis and systematic review
Yin ZHENG ; Zhenhua WU ; Cheng ZHANG ; Kexin RUAN ; Xiaolin GANG ; Hong JI
Chinese Journal of Tissue Engineering Research 2026;30(5):1260-1268
OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine>PH-350 adsorption column+conventional Western medicine>A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column>HA280 adsorption column+conventional Western medicine>PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column>A protein adsorption column+conventional western medicine>PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column>A protein adsorption column+conventional western medicine>PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine>leukocyte adsorption column>A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine>A protein adsorption column>leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine>leukocyte adsorption column>conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.
5.Safety and efficacy of immunoadsorption therapy for rheumatoid arthritis:a network meta-analysis and systematic review
Yin ZHENG ; Zhenhua WU ; Cheng ZHANG ; Kexin RUAN ; Xiaolin GANG ; Hong JI
Chinese Journal of Tissue Engineering Research 2026;30(5):1260-1268
OBJECTIVE:To evaluate the efficacy and safety of different immunosorbent columns in the treatment of rheumatoid arthritis through a network meta-analysis,and provide evidence-based basis for clinical diagnosis and treatment.METHODS:By computer,the databases of VIP,WanFang,CNKI,PubMed,CBM,CochraneLibrary,and Web of Science were searched for published cohort studies of immunosorbent column for the treatment of rheumatoid arthritis,with a time limit until August 2024.The quality of the included randomized controlled trials was assessed using the Cochrane5.4 manual.The quality of retrospective cohort studies were evaluated via the Newcastle-Ottawa Scale(NOS).Bayesian network meta-analysis was performed using R4.1.1 software.RESULTS:A total of 13 studies were included,with a total sample size of 891 cases,and 4 immunosorbent columns were included.The results of the network meta-analysis showed that the top three orders that reduce C-reactive protein level:HA280 adsorption column+conventional Western medicine>PH-350 adsorption column+conventional Western medicine>A protein adsorption column;the top three orders that reduce erythrocyte sedimentation rates:leukocyte adsorption column>HA280 adsorption column+conventional Western medicine>PH-350 adsorption column+conventional western medicine;the top three orders that reduce swollen joint count:leukocyte adsorption column>A protein adsorption column+conventional western medicine>PH-350 type adsorption column+conventional Western medicine;the top three orders that reduce tenderness joint counts:leukocyte adsorption column>A protein adsorption column+conventional western medicine>PH-350 adsorption column+conventional Western medicine;the top three orders that reduce patients' disease activity evaluation:PH-350 adsorption column+conventional western medicine>leukocyte adsorption column>A protein adsorption column;the top three orders that reduce visual analogue scale scores:PH-350 adsorption column+conventional Western medicine>A protein adsorption column>leukocyte adsorption column;the top three orders that reduce physician's disease activity assessment:PH-350 adsorption column+conventional Western medicine>leukocyte adsorption column>conventional Western medicine.CONCLUSION:Based on the 13 articles,in terms of reducing C-reactive protein level,HA280 adsorption column and conventional Western medicine are the preferred choice.In terms of reducing erythrocyte sedimentation rate,swollen joint count,and tender joint count,leukocyte adsorption column is the preferred choice.In terms of reducing patient's disease activity evaluation,physician's disease activity evaluation and visual analogue scale scores,PH-350 adsorption column and conventional Western medicine are the first choice.Different immunosorbent columns can be reasonably and accurately selected according to the patient's specific conditions.
6.Quality of leukoreduced pooled concentrated platelets prepared from whole blood under different storage temperatures and durations
Huijuan AN ; Hong SHAN ; Zheng LIU ; Jiaojiao ZHANG ; Jiaojie WANG ; Lili BIE ; Min LIU
Chinese Journal of Blood Transfusion 2026;39(5):603-609
Objective: To compare the in vitro quality differences of leukoreduced pooled concentrated platelets prepared from whole blood preserved at different temperatures and for various durations, determine the safe time window for refrigerated whole blood in platelet preparation, and provide experimental evidence for optimizing blood component preparation procedures and improving the comprehensive utilization rate of blood resources. Methods: A total of 324 units of 400 mL ACD-B anticoagulated whole blood were randomly divided into two groups and stored at 4℃ and 22℃, respectively. The buffy coat was separated at three time intervals: <6 h, 6-12 h, and >12 h (≤18 h) post-collection, and allowed to rest overnight at 22℃. On the following day, the buffy coats from each group were pooled to prepare leukoreduced pooled platelet concentrates (LPPCs). Cell counts were performed, and metabolic parameters including pH, glucose, and lactate levels were measured to evaluate metabolic status. Platelet in vitro function and activation were assessed by thromboelastography (TEG), platelet aggregation rate, and the expression of PAC-1 and CD62P. The differences between the two groups were compared. Results: For pooled concentrated platelets prepared from whole blood stored at 4℃ and 22℃ for <6 h and 6-12 h, there were no significant differences in platelet count, pH, glucose levels, lactic acid levels, thromboelastography (TEG), platelet aggregation rate, or platelet activation rate (P>0.05). With prolonged refrigeration time of whole blood, compared with pooled concentrated platelets prepared from whole blood stored at 22℃ for >12 h but ≤18 h, those prepared from whole blood stored at 4℃ for >12 h but ≤18 h showed a decreased platelet count (1 152.83±180.08 vs 1 368.83±134.86, P=0.040), a significantly increased ADP-induced aggregation rate (26.82±6.59 vs 13.88±10.21, P=0.030), and significantly elevated expression rates of PAC-1 and CD62P (72.64±6.74 vs 63.28±5.97, P=0.030). However, there were no significant differences in pH, glucose content, lactate content, or thromboelastography (P>0.05). Conclusion: There was no significant difference in the in vitro count, function, or activation of pooled concentrated platelets prepared from whole blood stored at 4℃ and 22℃ within 12 hours. However, statistically significant differences were observed between the mixed concentrated platelets prepared from whole blood stored at 4℃ and those stored at 22℃ for more than 12 hours but not exceeding 18 hours. These findings can provide a reference for the preparation methods and clinical application of refrigerated platelets.
7.Differences in Responses to Neoadjuvant Anti-HER2 Therapy between HER2 2+/ISH+ and HER2 3+ in HER2-Positive Breast Cancer
Lingjun MA ; Ran ZHENG ; Lingyun XU ; Ying ZHU ; Hong YIN ; Xiaoqing ZHANG ; Rong DENG ; Jue WANG ; Xiaoming ZHA
Cancer Research and Treatment 2026;58(2):501-512
Purpose:
Dual anti–human epidermal growth factor receptor 2 (HER2) drugs have become the standard regimen for neoadjuvant systemic treatment (NST) to HER2-positive breast cancer patients. However, the efficacy varies greatly among patients with different HER2 protein expression levels.
Materials and Methods:
A total of 575 HER2-positive breast cancer patients from multiple centers throughout China from 2013 to 2022 were retrospectively analyzed. We compared clinicopathological features in different HER2 immunohistochemistry classes (HER2 2+/in situ hybridization [ISH] + or HER2 3+), and their difference in response to NST and survival with single or dual anti-HER2 drugs. Drug sensitivity assays were used to evaluate different efficacy of anti-HER2 drugs in vitro.
Results:
Compared to HER2 3+ subgroup, the HER2 2+/ISH+ group had a higher proportion of hormone receptor–positive status (48.7% vs. 76.1%, p < 0.001), more HER2 protein loss after NST, lower pathological complete response (pCR) rate (46.07% vs. 16.24%, p < 0.001), and tended to have worse disease-free survival (DFS). In HER2 2+/ISH+ patients, treated with pertuzumab and trastuzumab in combination had no significant improvement in pCR (19.12% vs. 12.24%, p=0.287) and DFS (p=0.908) than using alone. Drug sensitivity assay showed poor efficacy with dual anti-HER2 drugs in HER2 2+/ISH+ cell lines; however, fam-trastuzumab deruxtecan drugs had a satisfactory effect.
Conclusion
Owing to the differences in clinicopathological features and treatment efficacy, we considered the HER2 2+/ISH+ group to be a distinct subtype and defined it as the HER2-moderate–positive subgroup. In this subgroup, dual anti-HER2 drugs did not exert significant improvement in pCR and DFS. Therefore, treatment optimization is warranted, with antibody-drug conjugate drugs as potential options.
8.A case of severe anemia caused by hookworm infection
Jun-ma YOU ; Hong-sheng ZHANG ; Hui-ni ZHENG
Acta Parasitologica et Medica Entomologica Sinica 2026;33(1):69-71
We report a case of a female farmer from the Yichang suburb, aged 68 years, who had been suffering from the infection for 3 years and had a history of seeking medical treatment at a community hospital and receiving blood transfusions. Her hemoglobin was as low as 28 g/L during this visit, and she had been ill for a long time with severe anemia. Routine stool examination revealed hookworm eggs. After active treatment, the patient recovered and was discharged from the hospital.
9.Environmental contamination status of norovirus outbreaks in schools and nurseries in Linhai City
ZHENG Jianjun, WANG Xi,HONG Danyang, LI Yaling, XU Qiumeng, ZHANG Huili, HAN Qian, LU Da, ZHENG Qiao
Chinese Journal of School Health 2025;46(4):601-603
Objective:
To investigate the environmental contamination of norovirus in nurseries and primary/secondary schools, so as to provide a scientific basis for effective prevention and control measures.
Methods:
A total of 483 external environmental samples were collected from 34 cluster outbreaks of norovirus gastroenteritis in kindergartens and primary/secondary schools in Linhai City from 2021 to 2024. Pathogen detection was conducted using a rapid nucleic acid extraction kit and realtime fluorescence RT-PCR, and the results were analyzed using the χ2 test or Fishers exact test.
Results:
Among the collected external environmental samples, the total positive rate of surface contamination was 13.66%. The positive rates in kindergartens and primary/secondary schools were 12.20% and 15.82%, respectively. In kindergartens, the five surfaces with the highest detection rates were desks/chairs (23.33%), toilet stool troughs (20.69%), urinal troughs (12.00%), washbasins/sinks (11.11%), and toilet mops (9.38%). In primary/secondary schools, the top five were toilet stool troughs (38.30%), urinal troughs (23.53%), toilet door handles (13.04%), toilet mops (12.50%), and drinking cups (11.11%). The difference in positive detection rates among different external environments in primary/secondary schools was statistically significant (Fishers exact probability test, P<0.01). The positive detection rate in sanitary toilets was higher than that in classroom environments (χ2=17.38), while the positive detection rate in classroom environments of kindergartens was higher than that in primary/secondary schools (χ2=5.42)(P<0.05).
Conclusions
Norovirus exhibits a high contamination rate in nurseries and schools, particularly in restroom areas. Strengthening sanitation and disinfection in highrisk environments, and improving hygiene awareness among children and staff, are essential for the effective prevent and control of norovirus.
10.Dr. Edmunds Grey Dimond: first foreign doctor to visit China for investigating acupuncture anesthesia.
Run HONG ; Zheng SUN ; Zilong ZHU ; Kuang YU ; Haitian SUN ; Jianbin ZHANG
Chinese Acupuncture & Moxibustion 2025;45(5):688-693
The international dissemination of Chinese acupuncture represents a successful model of medical and cultural exchange between the East and the West, as well as an exemplary case of Chinese culture going global. In 1971, following the announcement by Xinhua News Agency that "acupuncture anesthesia technology had achieved success", American medical educator Professor Edmunds Grey Dimond became the first foreign doctor to visit China for an investigation of acupuncture anesthesia. His efforts significantly contributed to the promotion of Chinese acupuncture within western medical communities. From the perspective of acupuncture humanities, this article reviews and analyzes Dimond's academic background, his journey to study acupuncture anesthesia in China, and his unique insights into acupuncture, exploring how his open-minded and objective approach facilitated the acceptance and dissemination of acupuncture anesthesia and acupuncture techniques in the West.
China
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Humans
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History, 20th Century
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Acupuncture Therapy/history*
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Acupuncture/history*
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Acupuncture Analgesia/history*
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History, 21st Century


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