1.Diagnosis and treatment of 281 elderly patients with pulmonary ground-glass opacity: A retrospective study in a single center
Lei SU ; Yi ZHANG ; Yan GAO ; Bing WEI ; Tengteng WANG ; Yuanbo LI ; Kun QIAN ; Peilong ZHANG ; Leiming WANG ; Xiuqin WEI
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(01):94-99
Objective To explore the diagnosis and treatment strategies for elderly patients with ground-glass opacity (GGO). Methods The imaging features and postoperative pathological findings of the elderly patients with pulmonary GGO receiving surgery in our hospital from 2017 to 2019 were retrospectively analyzed. The patients were divided into an elderly patient group and a non-elderly patient group based on their age. Results Finally 575 patients were included in the study. There were 281 elderly patients, including 83 males and 198 females, with an average age of (67.0±5.3) years. There were 294 non-elderly patients, including 88 males and 206 females, with an average age of (49.1±7.3) years. Compared with the non-elderly patients, elderly GGO patients showed the following distinct clinical features: long observation time for lesions (P=0.001), high proportion of rough edges of GGO (P<0.001), significant pleural signs (P<0.001) and bronchial signs (P<0.001), and high proportion of type Ⅱ-Ⅳ GGO (P<0.001), lobectomy type (P=0.013), and invasive lesions reported in postoperative pathology (P<0.001). There was no statistical difference in the average hospital stay between the two groups (P=0.106). Multivariate logistic regression analysis showed that GGO diameter and GGO type were the main factors affecting the operation. Observation time, GGO diameter, GGO type and pleural signs were the main influencing factors for postoperative pathological infiltrative lesions. The cut-off value of GGO diameter in predicting infiltrating lesions was 10.5 mm in the elderly patients group. Conclusion The size and type of GGO are important factors in predicting invasive lesions and selecting surgical methods. Elderly patients with radiographic manifestations of type Ⅱ-Ⅳ GGO lesions with a diameter greater than 10.5 mm should be closely followed up.
2.Effect of auricular therapy on sleep improvement and the GABAergic system pathway in an insomnia rat model
Hao CHEN ; Xifen ZHANG ; Xuesong WANG ; Yuanbo GAO ; Xuxin LI ; Xihui ZHENG ; Yu WANG ; Xiaojun ZHENG ; Haiping LI ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):138-148
Objective:
To investigate the effect of auricular therapy on sleep improvement and the GABAergic system pathway in a rat model of insomnia and to explore its possible mechanism.
Methods:
According to the random number table, 60 male SD rats were randomly divided into blank control, model, auricular point sticking, auricular bloodletting, and auricular bloodletting combined with sticking groups, with 12 rats per group. Insomnia was induced by intraperitoneal injection of p-chlorophenylalanine. After establishing the insomnia model, 36 rats were treated once a day with auricular point sticking or bloodletting for 5 consecutive days. After the intervention, the general condition and body weight of rats were observed; the righting reflex test was used to detect the sleep latency and duration; HE staining was used to observe the morphology of hypothalamic neuron cells; and an enzyme-linked immunosorbent assay was used to detect the GABA and glutamate content in rat serum. Immunohistochemistry(IHC) and real-time fluorescence quantitative PCR were used to detect GABA ARα1 and GABA ARγ2 protein and mRNA expression in the hypothalamus of rats, and Western blotting(WB) was used to detect GABA ARα1, GABA ARγ2, GAD65/67, GAT-1, and GABA-T protein expression in the hypothalamus of rats.
Results:
Compared with the blank control group, the model group had a lower body weight, a significantly shorter sleep duration (P<0.05), severe damage to the morphological structure of hypothalamic neurons with disordered cell arrangement, larger intercellular gaps, enlarged cell bodies, and a vacuolated appearance. All the intervention groups had significantly higher body weight and longer sleep duration than the model group (P<0.05). Compared with the other intervention groups, the auricular point sticking group had a longer sleep duration (P<0.05), and the hypothalamic neuron cells in all intervention groups improved, with the auricular point sticking group showing more apparent improvement. The model group had a lower GABA and higher glutamate contents, and GABA ARα1, GABA ARγ2, and GAD65/67 protein expression in the hypothalamus were lower than in the blank control group. In contrast, GAT-1 and GABA-T protein expression was higher, and GABA ARα1 and GABA ARγ2 mRNA expression was lower (P<0.05). The serum GABA content in the auricular point sticking and auricular bloodletting groups was higher, and the serum glutamate content in the auricular point sticking and auricular bloodletting combined sticking groups was lower than in the model group. GABA ARα1 mRNA expression in the hypothalamus of each intervention group was significantly increased, and GABA ARγ2 mRNA expression in the hypothalamus of the auricular point sticking and auricular bloodletting combined sticking groups increased. GABA ARα1(IHC, WB), GABA ARγ2(WB), and GAD65/67 protein expression in the hypothalamus of the auricular point sticking group increased, whereas GAT-1 and GABA-T protein expression decreased. GABA ARα1 and GABA ARγ2 protein expression(IHC, WB) in the hypothalamus of the auricular bloodletting group increased, whereas GABA-T protein expression decreased. GABA ARγ1(IHC) and GABA ARγ2(WB) protein expression in the hypothalamus of the auricular bloodletting combined sticking group increased, whereas GAT-1 and GABA-T protein expression decreased (P<0.05). Compared with in the inventation groups, the serum GABA content in the auricular point sticking group increased, the serum glutamate content decreased, GABA ARα1 and GABA ARγ2 mRNA expression in the hypothalamus increased, and GABA ARα1(IHC), GAD65/67 protein expression increased. In contrast, GABA-T protein expression decreased (P<0.05), and GABA ARγ2 protein expression(IHC) in the hypothalamus of the auricular bloodletting group increased (P<0.05).
Conclusion
Auricular therapy, particularly auricular point sticking, may have modulated the GABAergic system pathway by upregulating hypothalamic GABA ARα1, GABA ARγ2, and GAD65/67 protein expression while downregulating GAT-1 and GABA-T protein expression to alleviate symptoms in an insomnia rat model.
3.Study on surface microcirculation sensitization of acupuncture points related to cold coagulation and stasis syndrome in primary dysmenorrhea
Xuxin LI ; Xuesong WANG ; Miao LIN ; Mingjian ZHANG ; Yuanbo GAO ; Xifen ZHANG ; Hao CHEN ; Haiping LI ; Xiaojun ZHENG ; Xisheng FAN ; Jun LIU ; Juncha ZHANG ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2025;48(2):253-269
Objective:
To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging.
Methods:
Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated.
Results:
Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05).
Conclusion
With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.
4.Optimal regimen screening of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome.
Yuqiang SONG ; Yuanbo FU ; Sanfeng SUN ; Yali WEN ; Yinxia LIU ; Jie SUN ; Xin DU ; Xueting ZHANG ; Linbo SHEN ; Baijie LI ; Han YU ; Qingdai LI
Chinese Acupuncture & Moxibustion 2025;45(2):242-248
OBJECTIVE:
To screen the optimal regimen of acupuncture and moxibustion for obstructive sleep apnea hypopnea syndrome (OSAHS), so as to provide the evidences for clinical decision-making.
METHODS:
From 7 databases in Chinese and English i.e. the Full-Text Database of China Journal Network (CNKI), Wanfang Data Knowledge Service Platform (Wanfang), VIP Information Chinese Journal Service Platform (VIP), Chinese Biomedical Literature Database (SinoMed), PubMed, Web of Science (WOS) and Cochrane Library, randomized controlled trial (RCT) articals of OSAHS treated with acupuncture and moxibustion were searched. The quality of evidence was evaluated with the modified Jadad scale, the evaluation index was established and the optimal regimen of acupuncture and moxibustion for OSAHS was screened by multi-index decision analysis.
RESULTS:
A total of 10 RCTs were included, and the filiform needling therapy was optimal in treatment of OSAHS. The acupoints included Lianquan (CV23), Danzhong (CV17), Zhongwan (CV12), and bilateral Kongzui (LU6), Pishu (BL20), Fenglong (ST40), Zusanli (ST36), Yinlingquan (SP9) and Zhaohai (KI6). Zusanli (ST36) received the reinforcing method, Pishu (BL20) and Fenglong (ST40) were stimulated with the reducing technique, and the rest acupoints with the uniform reinforcing-reducing. Each acupoint was manually manipulated once every 10 min during the needle retention for 30 min. Acupuncture was delivered once a day, 5 times a week and for consecutive 4 weeks. Among the included literature, the severity of disease was not reported in detail, the filiform needling was the dominant intervention, the local acupoints such as Lianquan (CV23) and Panglianquan (Extra) were mainly selected. The apnea-hypopnea index and the minimum oxygen saturation were taken as the evaluation indexes, and the effect was evaluated in reference to the generally accepted standards. The attention to safety evaluation was insufficient, the report on methodology was not adequate and the quality was low.
CONCLUSION
Filiform needling is the dominant therapy of acupuncture and moxibustion for OSAHS, and the local acupoints are considered specially. But the quality of clinical research should be improved.
Humans
;
Moxibustion
;
Acupuncture Therapy
;
Sleep Apnea, Obstructive/therapy*
;
Acupuncture Points
;
Randomized Controlled Trials as Topic
5.Effect of moxibustion at "Shenque" (CV8) on the expression of BDNF and c-fos in the urinary control brain regions of rats with neurogenic bladder after spinal cord injury.
Han YU ; Yuanbo FU ; Huilin LIU ; Yuzhuo ZHANG ; Yutong NI ; Qingdai LI ; Yi XU
Chinese Acupuncture & Moxibustion 2025;45(5):638-645
OBJECTIVE:
To observe the effects of moxibustion at "Shenque" (CV8) on urodynamics and the expression of brain-derived neurotrophic factor (BDNF) and immediate early gene (c-fos) in pontine micturition center (PMC), periaqueductal gray (PAG), medial prefrontal cortex (mPFC) of neurogenic bladder (NB) rats after spinal cord injury.
METHODS:
Twenty-four SPF female SD rats were randomly divided into a sham-operation group (6 rats) and a modeling group (18 rats). In the modeling group, T9 complete spinal cord transection method was used to establish a neurogenic detrusor overactivity model, and the 12 rats with successful modeling were randomized into a model group and a moxibustion group, with 6 rats in each group. The rats in the moxibustion group were treated with ginger/salt-insulated moxibustion at "Shenque" (CV8), and 4 consecutive moxa cones were delivered in one intervention. Moxibustion was operated once daily and for 14 days. After intervention completion, the urodynamic indexes of rats in each group were detected. Fluorescence quantitative PCR was used to detect the mRNA expression of BDNF and c-fos in PMC, PAG and mPFC in rats. Western blot was used to detect the protein expression of BDNF and c-fos in PMC, PAG and mPFC.
RESULTS:
The rats in the sham-operation group did not show phasic detrusor contraction during bladder filling. Compared with the model group, the frequency and amplitude of the phasic detrusor contraction were reduced 5 min before urine leakage in the rats of the moxibustion group (P<0.05), and the duration of the first phasic detrusor contraction during bladder filling was prolonged (P<0.05). Compared with the sham-operation group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC increased in the model group (P<0.05). Compared with the model group, the mRNA and protein expression of BDNF and c-fos in PMC, PAG and mPFC decreased in the moxibustion group (P<0.05).
CONCLUSION
Moxibustion at "Shenque" (CV8) can improve the phasic contraction during bladder filling in NB rats after spinal cord injury, possibly by down-regulating the mRNA and protein expression of BDNF and c-fos in PMC, PAG, and mPFC.
Animals
;
Moxibustion
;
Female
;
Rats
;
Brain-Derived Neurotrophic Factor/metabolism*
;
Rats, Sprague-Dawley
;
Acupuncture Points
;
Spinal Cord Injuries/metabolism*
;
Urinary Bladder, Neurogenic/etiology*
;
Proto-Oncogene Proteins c-fos/metabolism*
;
Humans
;
Urinary Bladder/physiopathology*
;
Brain/metabolism*
;
Urination
6.Preliminary exploration of the symptom fluctuation after acupuncture for idiopathic tinnitus.
Baiqing WANG ; Yuanbo FU ; Baijie LI ; Xueting ZHANG ; Yuhan ZENG ; Yutong NI ; Huilin LIU ; Peng CHEN ; Xiaobai XU ; Bingcong ZHAO
Chinese Acupuncture & Moxibustion 2025;45(10):1477-1483
After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans
;
Tinnitus/physiopathology*
;
Acupuncture Therapy
;
Male
;
Female
7.The value of liver imaging reporting and data system version 2018 features in predicting microvascular invasion of hepatocellular carcinoma
Zhiwei LU ; Yuanbo ZHAO ; Shaobin ZHANG ; Lin ZHANG
Journal of Practical Radiology 2024;40(2):244-248
Objective To investigate the value of liver imaging reporting and data system version 2018(LI-RADS v2018)features in predicting microvascular invasion(MVI)of hepatocellular carcinoma(HCC).Methods Ninety-two patients diagnosed as LR-5 and pathologically confirmed HCC were included and divided into MVI positive group and MVI negative group.The major and ancillary features of LI-RADS v2018 were compared between the two groups.Logistic univariate and multivariate regression analyses were used to obtain the independent risk factors for MVI,and the value of differential features in predicting MVI was also assessed using the receiver operating characteristic(ROC)curve.Results In the MVI positive group,the pathological grade of HCC was higher than that in the MVI negative group,with larger tumor diameter and higher incidence of mosaic architecture and corona enhancement.However,there was no difference in any other features.In logistic univariate analysis,tumor diameter,mosaic architecture and corona enhancement were independent risk factors for predicting the MVI,with area under the curve(AUC)values of 0.763 and 0.628 and 0.670 for the diagnosis of MVI,respectively.Conclusion In high-risk LR-5 population,tumor diameter,mosaic architecture and corona enhancement can help to predict the MVI.Accurate identification of LI-RADS v2018 features may facilitate personalized management of HCC patients.
8.Comparative study on the effects of different acupuncture technique on macrophage polarization in a mouse model of simple endometrial hyperplasia
Junya LIU ; Yunfeng LI ; Jing LYU ; Wenchao ZHENG ; Guang ZUO ; Xuesong WANG ; Xisheng FAN ; Juncha ZHANG ; Jun LIU ; Xuxin LI ; Xifen ZHANG ; Yuanbo GAO ; Yanfen SHE
Journal of Beijing University of Traditional Chinese Medicine 2024;47(9):1203-1210
Objective We aimed to observe the differences in the effects of different acupuncture technique on the endometrium of mice with simple endometrial hyperplasia model and to explore the potential mechanisms. Methods According to the random number tables,32 female C57BL/6J mice were divided into a blank control group,a model group,a quick needle group and a retaining needle group,with 8 mice in each group. A mouse model of simple endometrial hyperplasia was established using bilateral ovariectomy combined with estrogen loading. In the quick needle group,mice were punctured at the bilateral for "Yinbai"(SP1) points and withdrawn immediately,with the treatmeat performed once every other day for a total of 12 times. In the retaining needle group,mice were punctured at the bilateral "Yinbai"(SP1) points and the needles were retained for 15 min each time,with the treatment also performed once every other day for a total of 12 times. After the intervention,samples were collected. HE staining was used to observe morphological changes in the mouse uterine tissue;ELISA was used to detect serum estradiol level;flow cytometry was used to detect the ratio of M1 and M2 macrophages(M1/M2) and immunohistochemical method was used to measure the expression of CD86 and CD206 in uterine tissue;and Western blotting was used to detect the expression of interleukin-13 (IL-13) and interferon-γ(IFN-γ) in uterine tissue. Results The endometrium of mice in the model group showed simple hyperplasia. Compared with the blank control group,the endometrium of the model group was thickened (P<0.01);the level of estradiol in the serum was increased (P<0.01);M1/M2 in uterine tissues was decreased (P<0.01),the expression of CD86 was decreased (P<0.01),and the positive expression of CD206 was increased (P<0.01);and the level of IFN-γ protein expression in uterine tissues was decreased (P<0.01),and the expression of IL-13 protein was increased (P<0.01). Compared with the model group,the endometrial thicknesses of the quick needle group and the retaining needle group were reduced (P<0.05),the levels of estradiol in serum were reduced (P<0.05),M1/M2 in uterine tissues increased (P<0.01),and the reduction of CD206 positive expression,and IL-13 protein expression reduced (P<0.01);the level of CD86 positive expression,IFN-γ protein expression increased (P<0.01). Compared with the quick needle group,IL-13 protein expression increased in the retaining needle group (P<0.01).Conclusion Both quick needle and retaining needle may be through the regulation of the expression of IFN-γ and IL-13,thus prompting the polarization of macrophages from M2 to M1 type,inhibiting the pro-cell proliferative ability and tissue repair ability of M2 type macrophages,thus reducing the degree of endometrial hyperplasia,and the quick needle group was superior to the retaining needle group in regulating the expression of IL-13.
9.Postoperative Complications of Minimally Invasive Vaginal Contraction: A Report of Six Cases
Guojing CHANG ; Zenan XIA ; Xinran ZHANG ; Yuanbo KANG ; Hailin ZHANG ; Xiao LONG ; Lin ZHU
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1468-1474
In recent years, the number of patients with vaginal relaxation has increased year by year, and the minimally invasive vaginal contraction has been carried out more and more widely in clinical practice, but the treatment normalization and safety have not been thoroughly studied. We summarized six cases of characteristics and treatment measures for patients with various complications after minimally invasive vaginal contraction surgery from September 2021 to December 2023 at Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital. The patients' age ranged from 26 to 44 years. Two cases accepted vaginal contraction with embedded vaginal thread, and four accepted vaginal contraction with acellular allogenic dermis. One patient showed vaginal hyper-tightness, one patient showed subcutaneous suture nodules, two patients showed explosion of acellular allogenic dermis, and three patients showed vaginal infection symptoms such as yellow leucorrhea and peculiar smell. All patients had sexual pain and discomfort. One patient underwent vaginal orifice dilation, one patient underwent suture extraction and secondary vaginal contraction, one patient underwent acellular allogenic dermis extraction and immediate vaginal contraction, two patients underwent acellular allogenic dermis extraction and secondary vaginal contraction, and one patient underwent secondary vaginal contraction. The symptoms of all six patients were relieved after treatment. Despite the short operation time and fast postoperative recovery of minimally invasive vaginal contraction, there are still complications after surgery, causing physical and mental damage to patients. Plastic surgeons, therefore, should be cautious in the treatment process to avoid collateral damage, so that patients get the best treatment effect.
10.Postoperative Complications of Minimally Invasive Vaginal Contraction: A Report of Six Cases
Guojing CHANG ; Zenan XIA ; Xinran ZHANG ; Yuanbo KANG ; Hailin ZHANG ; Xiao LONG ; Lin ZHU
Medical Journal of Peking Union Medical College Hospital 2024;15(6):1468-1474
In recent years, the number of patients with vaginal relaxation has increased year by year, and the minimally invasive vaginal contraction has been carried out more and more widely in clinical practice, but the treatment normalization and safety have not been thoroughly studied. We summarized six cases of characteristics and treatment measures for patients with various complications after minimally invasive vaginal contraction surgery from September 2021 to December 2023 at Department of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital. The patients' age ranged from 26 to 44 years. Two cases accepted vaginal contraction with embedded vaginal thread, and four accepted vaginal contraction with acellular allogenic dermis. One patient showed vaginal hyper-tightness, one patient showed subcutaneous suture nodules, two patients showed explosion of acellular allogenic dermis, and three patients showed vaginal infection symptoms such as yellow leucorrhea and peculiar smell. All patients had sexual pain and discomfort. One patient underwent vaginal orifice dilation, one patient underwent suture extraction and secondary vaginal contraction, one patient underwent acellular allogenic dermis extraction and immediate vaginal contraction, two patients underwent acellular allogenic dermis extraction and secondary vaginal contraction, and one patient underwent secondary vaginal contraction. The symptoms of all six patients were relieved after treatment. Despite the short operation time and fast postoperative recovery of minimally invasive vaginal contraction, there are still complications after surgery, causing physical and mental damage to patients. Plastic surgeons, therefore, should be cautious in the treatment process to avoid collateral damage, so that patients get the best treatment effect.


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