1.Progress of mesenchymal stem cell-derived extracellular vesicles and combined bioscaffolds in the treatment of corneal alkali burns
Sataer Aishan ABUDOU ; Xia LI ; Ying ZHOU ; Xiaokang WANG
International Eye Science 2025;25(3):404-409
Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.
2.Progress of mesenchymal stem cell-derived extracellular vesicles and combined bioscaffolds in the treatment of corneal alkali burns
Sataer Aishan ABUDOU ; Xia LI ; Ying ZHOU ; Xiaokang WANG
International Eye Science 2025;25(3):404-409
Corneal alkali burns are a common form of corneal trauma, and their treatment has been a challenge in ophthalmology. Traditional treatments include anti-inflammatory, immunosuppressive, and corneal transplantation, with limited results. This review focuses on the research progress of mesenchymal stem cells(MSCs)and their derived extracellular vesicles(MSCs-EVs)in the treatment of corneal alkali burns. MSCs have the ability of self-renewal, multidirectional differentiation, and immunomodulation, and the MSCs-EVs inherit its function from MSCs. MSCs-EVs inherit the functions of MSCs and has lower immunogenicity and better biocompatibility, which provides a new avenue for ophthalmic treatment. In addition, bioscaffolds are used as scaffolds or drug delivery systems in tissue engineering to promote tissue regeneration due to their excellent biocompatibility and degradability. This article reviews the mechanism of action and research progress of MSCs-EVs and combined bioscaffolds in the treatment of corneal alkali burns, and explores their potential in promoting the repair of corneal alkali burns and improving vision. These findings provide new strategies for the treatment of corneal alkali burns and are expected to improve the prognosis of patients.
3.Decompression mechanism of symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous
Chunlin ZHANG ; Zhaohua HOU ; Xu YAN ; Yan JIANG ; Su FU ; Yongming NING ; Dongzhe LI ; Chao DONG ; Xiaokang LIU ; Yongkui WANG ; Zhengming CAO ; Tengyue YANG
Chinese Journal of Tissue Engineering Research 2025;29(9):1810-1819
BACKGROUND:Traditional surgery for lumbar disc herniation involves extensive excision of tissue surrounding the nerve for decompression and removal of protruding lumbar intervertebral discs,which poses various risks and complications such as nerve damage causing paralysis,lumbar instability,herniation recurrence,intervertebral space infection,and adjacent vertebral diseases. OBJECTIVE:To propose the symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous technique for lumbar spine symmetrically decompression,showing the induced resorption of herniated nucleus pulpous phenomenon and early clinical efficacy,and then analyze its decompression mechanism. METHODS:214 patients with lumbar disc herniation at Department of Orthopedics,First Affiliated Hospital of Zhengzhou University from March 2021 to May 2023 were enrolled in this study.Among them,81 patients received conservative treatment as the control group,and 133 patients received symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous treatment as the trial group.Before surgery,immediately after surgery(7-14 days),and early after surgery(over 1 year),MRI images were used to measure the volume changes of lumbar disc herniation.CT images were used to measure the posterior displacement distance of the lumbar spinous process ligament complex,as well as the width and height of the lateral recess.Japanese Orthopaedic Association scores were used to evaluate the patient's neurological function recovery. RESULTS AND CONCLUSION:(1)Control group:81 patients with lumbar disc herniation were treated conservatively,with a total of 171 herniated lumbar discs.The average follow-up time was(22.7±23.1)months.The first and second MRI measurements of 171 herniated lumbar discs showed herniated lumbar disc volumes of(551.6±257.9)mm3 and(792.2±330.4)mm3,respectively,with an average volume increase rate of(53.2±44.4)%,showing statistically significant differences(P<0.001).Out of 171 herniated lumbar discs,4 experienced natural shrinkage,with an absorption ratio of 2.3%(4/171)and an absorption rate of(24.5±9.9)%.(2)Trial group:133 patients with lumbar disc herniation had a total of 285 herniated lumbar discs.(1)Immediately after surgery:All patients were followed up immediately after surgery.229 out of 285 herniated lumbar discs experienced retraction,with an absorption ratio of 80.3%(229/285)and an average absorption rate of(21.5±20.9)%,with significant and complete absorption accounting for 6.5%.There were a total of 70 herniated lumbar discs in the upper lumbar spine,with an absorption ratio of 85.7%(60/70),an average absorption rate of(23.1±19.5)%,and a maximum absorption rate of 86.6%.There were 215 herniated lumbar discs in the lower lumbar spine,with an absorption ratio of 78.6%(169/215),an average absorption rate of(21.0±21.3)%,and a maximum absorption rate of 83.2%.Significant and complete absorption of the upper and lower lumbar vertebrae accounted for 5.7%and 6.5%,respectively,with no statistically significant difference(P>0.05).The average distance of posterior displacement of the spinous process ligament complex immediately after surgery was(5.2±2.8)mm.There were no significant differences in the width and height of the left and right lateral recess before and immediately after surgery(P>0.05).The Japanese Orthopaedic Association score immediately after surgery increased from(10.1±3.4)before surgery to(17.0±4.8),and the immediate effective rate after surgery reached 95.6%.(2)Early postoperative period:Among them,46 patients completed the early postoperative follow-up.There were 101 herniated lumbar discs,with an absorption ratio of 94%(95/101)and an average absorption rate of(36.9±23.7)%.Significant and complete absorption accounted for 30.6%,with a maximum absorption rate of 100%.Out of 101 herniated lumbar discs,3 remained unchanged in volume,with a volume invariance rate of 2.97%(3/101).Out of 101 herniated lumbar discs,3 had an increased volume of herniated lumbar discs,with an increase ratio of 2.97%(3/101)and an increase rate of(18.5±18.4)%.The Japanese Orthopaedic Association score increased from preoperative(9.3±5.1)to(23.5±4.0),with an excellent and good rate of 93.4%.(3)The early postoperative lumbar disc herniation absorption ratios of the control group and trial group were 2.3%and 85.9%,respectively,with statistically significant differences(P<0.001).(4)Complications:There were two cases of incision exudation and delayed healing in the trial group.After conservative treatment such as dressing change,no nerve injury or death occurred in the incision healing,and no cases underwent a second surgery.(5)It is concluded that symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous is a new method for treating lumbar disc herniation that can avoid extensive excision of the"ring"nerve and achieve satisfactory early clinical efficacy.It does not damage the lumbar facet joints or alter the basic anatomical structure of the lateral recess,fully preserves the herniated lumbar discs,and can induce significant or even complete induced resorption of herniated nucleus pulpous.Symmetrically adduction of lumbar decompression induced resorption of herniated nucleus pulpous provides a new basis and method for the clinical treatment of lumbar disc herniation.
4.Analysis of Animal Model Construction Methods of Different Subtypes of Gastroesophageal Reflux Disease Based on Literature
Mi LYU ; Kaiyue HUANG ; Xiaokang WANG ; Yuqian WANG ; Xiyun QIAO ; Lin LYU ; Hui CHE ; Shan LIU ; Fengyun WANG
Journal of Traditional Chinese Medicine 2025;66(13):1386-1394
ObjectiveTo collate and compare the characteristics and differences in the methods for constructing animal models of different subtypes of gastroesophageal reflux disease (GERD) based on literature, providing a reference for researchers in this field regarding animal model construction. MethodsExperimental studies related to GERD including reflux esophagitis (RE), nonerosive reflux disease (NERD) and Barrett's esophagus (BE) model construction from January 1, 2014 to January 27, 2024, were retrieved from databases such as CNKI, Wanfang, VIP, Web of Science, and Pubmed. Information on animal strains, genders, modeling methods including disease-syndrome combination models, modeling cycles were extracted; for studies with model evaluation, the methods of model evaluation were also extracted; then analyzing all those information. ResultsA total of 182 articles were included. SD rats were most frequently selected when inducing animal models of RE (88/148, 59.46%) and NERD (9/14, 64.29%). For BE, C57BL/6 mice were most commonly used (11/20, 55.00%). Male animals (RE: 111/135, 82.22%; NERD: 11/14, 78.57%; BE: 10/12, 83.33%) were the most common gender among the three subtypes. The key to constructing RE animal models lies in structural damage to the esophageal mucosal layer, gastric content reflux, or mixed reflux, among which forestomach ligation + incomplete pylorus ligation (42/158, 26.58%) was the most common modeling method; the key to constructing NERD animal models lies in micro-inflammation of the esophageal mucosa, visceral hypersensitivity, and emotional problems, and intraperitoneal injection of a mixed suspension of ovalbumin and aluminum hydroxide combined with acid perfusion in the lower esophagus (8/14, 57.14%) was the most common modeling method; the key to constructing BE animal models lies in long-term inflammatory stimulation of the esophageal mucosa and bile acid reflux, and constructing interleukin 2-interleukin 1β transgenic mice (7/25, 28.00%) was the most common modeling method. Adverse psychological stress was the most common method for inducing liver depression. ConclusionsThe construction key principles and methodologies for RE, NERD, and BE animal models exhibit significant differences. Researchers should select appropriate models based on subtype characteristics (e.g., RE focusing on structural damage, NERD emphasizing visceral hypersensitivity). Current studies show insufficient exploration of traditional Chinese medicine disease-syndrome combination models. Future research needs to optimize syndrome modeling approaches (e.g., composite etiology simulation) and establish integrated Chinese-Western medicine evaluation systems to better support mechanistic investigations of traditional Chinese medicine.
5.Level of coagulation factor Xin patients with venous thrombosis of lower limbs and its correlation with recurrence risk
Haijun JIANG ; Ronghua LI ; Guoping CHEN ; Li WANG ; Jun HOU ; Xiaokang CHENG ; Liming YU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):151-154
Objective To investigate the level of coagulation factor Ⅺ(FⅪ)in patients with venous thrombosis of lower limbs and its correlation with recurrence risk.Methods A total of 220 pa-tients with deep vein thrombosis(DVT)admitted in our hospital from February 2018 to February 2019 were enrolled as the study group,and another 50 healthy individuals taking physical exami-nation during same period served as the control group.After a 3 years followed,the study group ultimately included 197 cases,according to the results of restricted cubic spline(RCS),the study group was divided into low(FⅪ<10.3 U/L,94 cases),medium-(10.3-12.1 U/L,52 cases)and high-level groups(>12.1 U/L,51 cases).The plasma level of FⅪ was detected in the study group 1 month after the end of anticoagulant therapy,and the results were compared with those of the control group during physical examination.Cox model was used to analyze the influence of FⅪ on the recurrence of DVT,and RCS was employed to analyze the relationship between DVT recur-rence and FⅪ level.Kaplan-Meier curve was plotted to analyze the recurrence risk of DVT with different FⅪ levels.The patients from the study group were followed up for 3 years.Results The FⅪ level was significantly higher in the study group than the control group(P<0.05).During fol-low-up period,33 patients(16.75%)had DVT recurrence.The Cox model analysis after adjust-ment of sex and age showed that FⅪ level was a risk factor for DVT recurrence(P<0.05).When the FⅪ level was set into tertile and the risk ratio was calculated after adjustment,FⅪ<10.3 U/L,and the average FⅪ level at this stage was 9.2 U/L,the risk ratio was 0.82(95%CI:0.673-0.984);Patients with FⅪ between 10.3 and 12.1 U/L,and the average FⅪ at this stage was 11.4 U/L,the risk ratio of 1.04(95%CI:0.813-1.432).The those with FⅪ>12.1 U/L,and the average FⅪ at this stage was 13.8 U/L,hazard ratio of 1.38(95%CI:0.921-1.563).Kaplan-Meier curve analysis showed that the recurrence risk was 28.62%(95%CI:25.633-31.609),30.10%(95%CI:27.594-32.606)and 38.06%(95%CI:34.306-41.371),respectively for the low-,medium-,and high-level groups,with significant correlation among the three groups(x2=6.631,P=0.036).Conclusion Compared with healthy individuals,plasma FⅪ level is at a high level in the DVT patients.With the increment of FⅪ level,the risk of DVT recurrence increases.Two FⅪ levels,10.3 U/L and 12.1 U/L,can be used as reference points for the obvious increase of DVT recur-rence rate.
6.Application of double mediastinal drainage tubes in elderly patients with intrathoracic anastomotic leak after thoracoscopic Ivor-Lewis surgery
Chuanfei ZHAN ; Shilin CHEN ; Xiaokang SHEN ; Dongjie FENG ; Xiaojun WANG ; Weizhong SHEN ; Feng JIANG ; Qin ZHANG ; Lin XU
Chinese Journal of Geriatrics 2024;43(1):56-59
Objective:To investigate the clinical significance of intraoperative prepositioning of dual mediastinal drains in elderly patients developing anastomotic leakage(AL)after a total endoscopic Ivor-Lewis procedure.Methods:This retrospective case-control study analyzed the clinical data of 500 elderly patients who underwent total endoscopic Ivor-Lewis surgery for esophageal or cardia cancer from January 2020 to December 2022.In the control group, one mediastinal drainage tube was placed intraoperatively, while in the study group, two mediastinal drainage tubes were placed.Both groups had a chest tube placed conventionally.The study compared the incidence of anastomotic leak(AL)at 1 month postoperatively, inflammatory indexes in patients with AL, grading of AL, rate of nasal fistula placement, incision infection, anastomotic stenosis, and incidence of hoarseness.Additionally, it compared ICU occupancy, ventilator use, and ICU length of stay between the two groups.Results:The analysis included clinical data from 455 elderly patients.Among the patients who developed AL, the study group had significantly lower peak body temperature[(39.58±1.03)℃ vs.(38.05±0.56)℃, t=4.298, P<0.05], white blood cell count[(18.63±3.35)×10 9/L vs.(14.28±2.78)×10 9/L, t=3.450, P<0.05], and C-reactive protein(CRP)levels[(154.66±41.64)mg/L vs.(122.19±31.29)mg/L, t=2.131, P<0.05]. The study group also had a significantly lower grading of AL and rate of nasal fistula placement(82.4% vs.30.0%, P<0.05). In terms of ICU indicators, the study group had a significantly lower ICU admission rate(64.7% vs.10.0%, P<0.05), shorter period of ventilator use[(6.47±8.15)days vs.(0.90±2.23)days, t=2.62, P<0.05], and shorter ICU stay[(11.70±8.89)days vs.(4.70±6.27)days, t=2.184, P<0.05]. Conclusions:Double mediastinal drainage tubes, have been found to significantly alleviate inflammation, decrease the rate of nasal fistula placement and ICU admission, and shorten the length of ICU stay in elderly patients.Therefore, they are considered safe and deserving of clinical promotion.
7.Prevalence and associated risk factors of retinopathy of prematurity in preterm infants with gestational age ≤34 weeks
Xiaokang WANG ; Yifei LIANG ; Yanping ZHU
Chinese Journal of Child Health Care 2024;32(2):187-190
【Objective】 To understand the prevalence of retinopathy (ROP) in preterm infants with gestational age ≤34 weeks in the First Affiliated Hospital of Xinjiang Medical University, and to analyze the associated risk factors, so as to provide a basis for early screening of high-risk premature infants. 【Methods】 A retrospective analysis was conducted on the relevant case data of hospitalized premature infants with gestational age ≤34 weeks in neonatal intensive care unit (NICU) of the First Affiliated Hospital of Xinjiang Medical University from June 2015 to June 2020. Infants were divided into ROP group and non-ROP group based on the results of fundus screening. Relevant data were collected to analyze the relevant risk factors for ROP in premature infants. 【Result】 A total of 1 738 premature infants with gestational age ≤34 weeks were included, with 292 cases (16.8%) in ROP group and 1 446 cases in non-ROP group. Logistic regression analysis revealed that bronchopulmonary dysplasia(BPD) (OR=3.379, 95%CI:1.835 - 6.221), anemia (OR=7.388, 95%CI: 4.262 - 12.806), receiving blood transfusion treatment (OR=2.129, 95%CI: 1.278 - 3.547), oxygen requirement time >7 days (OR=3.429, 95%CI: 2.309 - 5.094), and the fraction of inspired oxygen greater than 40% (OR=2.541, 95%CI: 1.540 - 4.193) were independent risk factors for the occurrence of ROP. Among these patients, 167 eyes (103 patients) received treatment of ROP, including 108 eyes treated with intraocular injection of Rizumab, 35 eyes treated with fundus laser, and 24 eyes treated with combination of both. All patients had acceptable outcomes during the follow-up. 【Conclusions】 Premature infants with anemia, BPD, receiving blood transfusion treatment, oxygen requirement time >7 days, and the fraction of inspired oxygen >40% are at high risk of developing ROP. Standardized fundus screening and timely treatment measures are essential to reduce the risk of visual impairment in premature infants.
8.Staged Treatment of Ulcerative Colitis based on the Experience in Treating Dysentery from Cold-fire Accumulation
Xiaokang WANG ; Mi LYU ; Jiayan HU ; Xijun QIAO ; Kunli ZHANG ; Wenxi YU ; Yuqian WANG ; Fengyun WANG
Journal of Traditional Chinese Medicine 2024;65(7):697-702
Referring to ZHANG Xichun's experience in treating dysentery from cold-fire accumulation, the treatment of ulcerative colitis (UC) in this paper can be divided into three stages including cold-fire accumulation stage, excessive heat and putrid intestine stage, and healthy qi deficiency and pathogen lingering stage. For people with slippery and excess pulse in the cold-fire accumulation stage, Xiaochengqi Decoction (小承气汤) added with Baishao (Radix Paeoniae Alba) and Gancao (Radix et Rhizoma Glycyrrhizae) can be used for purgation, while those with deficient pulse, Huazhi Decoction (化滞汤) or Xieli Decoction (燮理汤) can be used. In the excessive heat and putrid intestine stage, Tongbian Baitouweng Decoction (通变白头翁汤) and Jiedu Shenghua Elixir (解毒生化丹) are suggested. In the healthy qi deficiency and pathogen lingering stage, it is advised to use Jiedu Shenghua Elixir added with Shanyao (Rhizoma Dioscoreae), and Sanbao Porridge (三宝粥). Additionally, the medication rules, dosage and administration characteristics of Huanglian (Rhizoma Coptidis)-Rougui (Cortex Cinnamomi), Yadanzi (Fructus Bruceae), Diyu (Radix Sanguisorbae), Shanyao and Liuhuang (Sulphur) by ZHANG Xichun have been summarized with the help of modern pharmacological research, so as to provide new ideas for the treatment of UC by TCM.
9.Association between congenital hypothyroidism and in-hospital adverse outcomes in very low birth weight infants
Sha ZHU ; Jing XU ; Ranran SHI ; Xiaokang WANG ; Maomao SUN ; Shina LI ; Lingling GAO ; Yuanyuan LI ; Huimin WEN ; Changliang ZHAO ; Shuai LI ; Juan JI ; Cuihong YANG ; Yonghui YU
Chinese Journal of Pediatrics 2024;62(1):29-35
Objective:To investigate the association between congenital hypothyroidism (CH) and the adverse outcomes during hospitalization in very low birth weight infants (VLBWI).Methods:This prospective, multicenter observational cohort study was conducted based on the data from the Sino-northern Neonatal Network (SNN). Data of 5 818 VLBWI with birth weight <1 500 g and gestational age between 24-<37 weeks that were admitted to the 37 neonatal intensive care units from January 1 st, 2019 to December 31 st, 2022 were collected and analyzed. Thyroid function was first screened at 7 to 10 days after birth, followed by weekly tests within the first 4 weeks, and retested at 36 weeks of corrected gestational age or before discharge. The VLBWI were assigned to the CH group or non-CH group. Chi-square test, Fisher exact probability method, Wilcoxon rank sum test, univariate and multivariate Logistic regression were used to analyze the relationship between CH and poor prognosis during hospitalization in VLBWI. Results:A total of 5 818 eligible VLBWI were enrolled, with 2 982 (51.3%) males and the gestational age of 30 (29, 31) weeks. The incidence of CH was 5.5% (319 VLBWI). Among the CH group, only 121 VLBWI (37.9%) were diagnosed at the first screening. Univariate Logistic regression analysis showed that CH was associated with increased incidence of extrauterine growth retardation (EUGR) ( OR=1.31(1.04-1.64), P<0.05) and retinopathy of prematurity (ROP) of stage Ⅲ and above ( OR=1.74(1.11-2.75), P<0.05). However, multivariate Logistic regression analysis showed no significant correlation between CH and EUGR, moderate to severe bronchopulmonary dysplasia, grade Ⅲ to Ⅳ intraventricular hemorrhage, neonatal necrotizing enterocolitis in stage Ⅱ or above, and ROP in stage Ⅲ or above ( OR=1.04 (0.81-1.33), 0.79 (0.54-1.15), 1.15 (0.58-2.26), 1.43 (0.81-2.53), 1.12 (0.70-1.80), all P>0.05). Conclusion:There is no significant correlation between CH and in-hospital adverse outcomes, possibly due to timely diagnosis and active replacement therapy.
10.Study on Distribution of Syndrome Elements in Irritable Bowel Syndrome Based on Factor Analysis and Clustering Analysis
Yuxi WANG ; Mi LYU ; Kunli ZHANG ; Jiayan HU ; Wenxi YU ; Xiyun QIAO ; Xiaokang WANG ; Fengyun WANG
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(12):163-168
Objective To investigate the distribution of TCM syndromes and syndrome elements of irritable bowel syndrome(IBS);To provide reference for clinical TCM syndrome differentiation and treatment.Methods The patients with IBS who filled in the questionnaire were collected from 18 tertiary Chinese medicine hospitals in China from November 2019 to December 2022,including Xiyuan Hospital,China Academy of Chinese Medical Sciences,Guangdong Provincial Hospital of Traditional Chinese Medicine,the First Affiliated Hospital of Henan University of Traditional Chinese Medicine.The contents of questionnaire included the patients'general condition,medical history(onset time,condition changes),Rome Ⅳ symptom diagnostic scale,somatic symptom cluster scale,quality of life scale,hospital anxiety and depression scale,TCM syndromes,etc.The methods of factor analysis and systematic clustering analysis were used,the factors of disease and syndrome were extracted,and the classification of TCM syndrome types was summarized.Results Totally 157 patients were included,87 were male and 70 were female.The age was from 18 to 74 years old.The longest course of disease was 30 years and the shortest was 3 months,with an average of(48.31±5.61)months.Anxiety score:was 3.66±0.30,depression score was 3.39±0.28.The most common TCM symptom was emotional distress(83.4%),followed by diarrhea(80.9%)and abdominal pain(72.6%).The results of factor analysis showed that rotation finally converged after 16 iterations,and 8 common factors and 33 variables were obtained,with a cumulative contribution rate of 60.016%.The sites of IBS were mainly distributed in liver,spleen,large intestine and stomach.The main syndrome factors were qi stagnation,phlegm,dampness,heat and yang deficiency.The results of clustering analysis of 8 common factors showed that the main TCM syndrome types were liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome,and liver-stomach digression syndrome.The main TCM syndrome of diarrhea-predominant IBS was liver stagnation and spleen deficiency syndrome,and the main TCM syndrome of mixed type and constipation type was damp-heat accumulation syndrome.There were statistically significant differences in the distribution of TCM syndrome types in patients with different types(P<0.05).Conclusion The location of IBS is mainly in liver,spleen and large intestine,especially in liver.The TCM syndrome types are mainly liver depression and qi stagnation syndrome,damp-heat internal accumulation syndrome,liver depression and spleen deficiency syndrome.

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