1.Historical Evolution and Key Information Research on Classic Formula Puji Xiaoduyin
Lianchao ZHU ; Lyuyuan LIANG ; Jing TANG ; Jialei CAO ; Ziming XU ; Huizhen ZHANG ; Zhidan GUO ; Rongze MA ; Zhengshao ZHANG ; Bingqi WEI ; Xiubo DU ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):238-247
Puji Xiaoduyin, a specialized formula for the swollen-head epidemic, was recorded in the Catalogue of Ancient Classical Formula (the Second Batch)-Han Medicine, published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name, historical origin, drug dosage, herb origin, processing methods, decocting methods, function, and clinical applications. Additionally, this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were: Scutellariae Radix and Coptidis Rhizoma (20.65 g each), Ginseng Radix et Rhizoma 12.39 g, Scrophulariae Radix, Citri Reticulatae Pericarpium, and Glycyrrhizae Radix et Rhizoma (8.26 g each), Forsythiae Fructus, Arctii Fructus, Isatidis Radix, and Lasiosphaera Calvatia (4.13 g each), Bombyx Batryticatus and Cimicifugae Rhizoma (2.891 g each), Bupleuri Radix and Platycodonis Radix (8.26 g each). These medicines were grounded to fine powder. One dose, including 20.65 g of the powder, was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag, the medicine should be taken warm frequently. In the formula, Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat, removing stagnation and dissipating mass, the formula is specialized in swollen-head epidemic, pestilence, red and swelling head, face, and neck, dry mouth and tongue, as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory, dermal, ophthalmologic, otolaryngologic, and nervous systems. The formula is most frequently used for respiratory diseases, with a wide range of symptoms including parotitis/mumps (66 times), followed by tonsillitis (28 times). In conclusion, the broadly applied formula has accurate efficacy and great development value.
2.Historical Evolution and Key Information Research on Classic Formula Puji Xiaoduyin
Lianchao ZHU ; Lyuyuan LIANG ; Jing TANG ; Jialei CAO ; Ziming XU ; Huizhen ZHANG ; Zhidan GUO ; Rongze MA ; Zhengshao ZHANG ; Bingqi WEI ; Xiubo DU ; Bingxiang MA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):238-247
Puji Xiaoduyin, a specialized formula for the swollen-head epidemic, was recorded in the Catalogue of Ancient Classical Formula (the Second Batch)-Han Medicine, published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name, historical origin, drug dosage, herb origin, processing methods, decocting methods, function, and clinical applications. Additionally, this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were: Scutellariae Radix and Coptidis Rhizoma (20.65 g each), Ginseng Radix et Rhizoma 12.39 g, Scrophulariae Radix, Citri Reticulatae Pericarpium, and Glycyrrhizae Radix et Rhizoma (8.26 g each), Forsythiae Fructus, Arctii Fructus, Isatidis Radix, and Lasiosphaera Calvatia (4.13 g each), Bombyx Batryticatus and Cimicifugae Rhizoma (2.891 g each), Bupleuri Radix and Platycodonis Radix (8.26 g each). These medicines were grounded to fine powder. One dose, including 20.65 g of the powder, was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag, the medicine should be taken warm frequently. In the formula, Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat, removing stagnation and dissipating mass, the formula is specialized in swollen-head epidemic, pestilence, red and swelling head, face, and neck, dry mouth and tongue, as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory, dermal, ophthalmologic, otolaryngologic, and nervous systems. The formula is most frequently used for respiratory diseases, with a wide range of symptoms including parotitis/mumps (66 times), followed by tonsillitis (28 times). In conclusion, the broadly applied formula has accurate efficacy and great development value.
3.Mechanism study on regulation of the LGALS3/PI3K/AKT signaling pathway by Paris polyphylla saponin Ⅱ in inhibiting the malignant biological behaviors of thyroid cancer cells
SUN Jianwei1 ; ZHANG Yan2 ; DU Zefei3 ; RUAN Xiaohui4 ; ZHENG Mengyang1 ; LIANG Haifeng2
Chinese Journal of Cancer Biotherapy 2026;33(3):270-279
[摘 要] 目的:探究重楼皂苷Ⅱ(PPⅡ)抑制甲状腺癌(TC)恶性生物学行为的分子机制。方法:常规培养甲状腺癌细胞TPC1,实验分为sh-NC、sh-可溶性半乳糖凝集素3(sh-LGALS3)、OE-NC、OE-LGALS3和 OE-LGALS3 + PPⅡ组,用转染试剂将应用质粒转染至各组TPC1细胞中。qPCR法检测TPC1细胞中LGALS3 mRNA的表达,WB法检测各组TPC1细胞中LGALS3、PI3K/AKT信号通路相关蛋白的表达,CCK-8法、Transwell实验、划痕愈合实验和流式细胞术分别检测各组TPC1细胞增殖、迁移和侵袭能力,以及细胞凋亡情况。结果:PPⅡ抑制TPC1细胞的增殖、迁移和侵袭,并诱导其凋亡(均P < 0.000 1)。数据库数据分析显示LGALS3在甲状腺癌组织中高表达(P < 0.001)且是PPⅡ的靶基因。LGALS1在TPC1细胞中呈高表达(P < 0.000 1),敲减LGALS3抑制TPC1细胞的恶性生物学行为,并促进其凋亡(均P < 0.000 1),PPⅡ通过抑制LGALS3 mRNA和蛋白的表达(P < 0.01或P < 0.001)从而抑制TPC1细胞的恶性生物学行为(P < 0.01或P < 0.000 1),PPⅡ抑制LGALS3表达抑制PI3K/AKT信号通路的激活水平(P <0.001或P <0.000 1),LGALS3通过PI3K/AKT信号通路促进TPC1细胞的恶性生物行为(P < 0.000 1)。结论:PPⅡ通过抑制TPC1细胞中LGALS3的表达,缓解PI3K/AKT信号通路的过度激活从而发挥抑癌作用。
4.Genetic analysis and reproductive intervention for 46 Chinese pedigrees affected with Hereditary multiple exostoses.
Lilan SU ; Xiao HU ; Jing DAI ; Zhengxing WAN ; Duo YI ; Shuangfei LI ; Liang HU ; Yueqiu TAN ; Fei GONG ; Ge LIN ; Guangxiu LU ; Qianjun ZHANG ; Juan DU ; Wenbin HE
Chinese Journal of Medical Genetics 2026;43(4):253-258
OBJECTIVE:
To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention.
METHODS:
Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010).
RESULTS:
In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born.
CONCLUSION
This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans
;
Female
;
Male
;
Pedigree
;
Exostoses, Multiple Hereditary/diagnosis*
;
N-Acetylglucosaminyltransferases/genetics*
;
Adult
;
Exostosin 1
;
Asian People/genetics*
;
Genetic Testing
;
Exostosin 2
;
Mutation
;
China
;
Prenatal Diagnosis
;
Pregnancy
;
Genetic Counseling
;
Preimplantation Diagnosis
;
Exome Sequencing
;
East Asian People
5.Mechanism of ductular reaction and related treatment strategies
Jiayan SHAN ; Huaqian XU ; Chengzhi BAI ; Liang ZHANG ; Chao DU ; Yong ZHANG ; Shanhong TANG
Journal of Clinical Hepatology 2026;42(3):733-738
Ductular reaction (DR) refers to the adaptive pathological changes that occur after hepatobiliary injury, and it is essentially a repair response involving the proliferation, fibrosis, and inflammation of biliary epithelial cell (BEC). With the understanding of the biological function of BEC, the potential value of DR in disease prognosis and treatment has gradually become a research hotspot. This article systematically reviews the molecular mechanism of DR, its potential as a therapeutic target, and future development directions, as well as novel therapies suggested by targeting these molecular mechanisms, in order to provide a new direction for overcoming current bottlenecks in the treatment of bile duct diseases.
6.Mechanism of Shenfukang capsule in ameliorating renal interstitial fibrosis by regulating cellular crosstalk via the STAT3/YAP pathway
Wei DU ; Yufang YANG ; Yanhong LIAO ; Xiaoqin ZOU ; Zhiwei LIANG ; Xiangqian FENG ; Xiaobin ZHONG
China Pharmacy 2026;37(12):1547-1552
OBJECTIVE To investigate the mechanism by which Shenfukang capsule (SFK) ameliorates renal interstitial fibrosis (RIF) by regulating macrophage-fibroblast crosstalk via the signal transducer and activator of transcription 3 (STAT3)/Yes-associated protein (YAP) pathway. METHODS RAW264.7 macrophages were induced to polarize with transforming growth factor-β 1 (TGF-β 1 ). Subsequently, a non-contact co-culture system of macrophages with renal fibroblasts NRK-49F, as well as a non-contact co-culture system of macrophages with YAP-knockdown renal fibroblasts, were established. Cells were treated with low, medium, and high concentrations (4, 8, 16 μg/mL) of SFK, as well as a STAT3 inhibitor (STAT3-I,1.64 μg/mL) and losartan potassium tablets (positive control, 0.28 μg/mL), for 48 h. After intervention, the protein and mRNA expression levels of CD86, CD163, and STAT3 in macrophages, as well as CD86, F4/80, and STAT3 mRNA, were detected. In co-cultured renal fibroblasts, the protein and mRNA expression levels of α -smooth muscle actin ( α -SMA), Vimentin, collagen type Ⅰ (Col-Ⅰ), matrix metalloproteinase-1 (MMP-1), and YAP were detected. In co-cultured YAP-knockdown renal fibroblasts, the protein and mRNA expression levels of α -SMA, Vimentin, and MMP-1 were also detected. RESULTS Following TGF-β 1 induction, the protein expression levels of CD86, CD163, and STAT3, as well as the mRNA expression levels of CD86, F4/80, and STAT3 in macrophages were significantly increased ( P <0.05). The conditioned medium from polarized macrophages activated renal fibroblasts, as evidenced by significantly increased protein and mRNA expression levels of α -SMA, Vimentin, Col-Ⅰ, and YAP, and significantly decreased protein and mRNA expression levels of MMP-1 in renal fibroblasts ( P <0.05). Treatment with SFK and STAT3-I reversed the changes in the above indicators, with the medium concentration SFK group showing stronge r effects on some indicators than the low and high concentration groups. In the non-contact co-culture experiment of macrophages and YAP-knockdown renal fibroblasts, there were no statistically significant differences in the protein and mRNA expression of α-SMA, Vimentin, and MMP-1 among the groups. CONCLUSIONS SFK can inhibit macrophage-renal fibroblast crosstalk by blocking the STAT3/YAP pathway, thereby delaying the progression of RIF.
7.Association between depressive symptoms and risk of stroke and all-cause mortality in young and middle-aged adults
Xianwang WANG ; Qinghui YUAN ; Juan DU ; Liang CHEN ; Dan LI ; Xiaopei ZHANG ; Yangyang TIAN
Sichuan Mental Health 2026;39(3):246-254
BackgroundCurrent studies on the relationship between depressive symptoms and the risks of stroke and all-cause mortality mostly focus on the elderly population or high-risk groups with chronic diseases. The long-term impact of depressive symptoms in young and middle-aged people on the risks of stroke and all-cause mortality still lacks systematic assessment, and the relevant evidence is insufficient. ObjectiveTo explore the association between depressive symptoms and the risks of stroke and all-cause mortality in young and middle-aged adults, thereby expanding the risk evidence in this age group and providing epidemiological basis for early identification of high-risk individuals and the development of targeted intervention strategies. MethodsBased on data from the National Health and Nutrition Examination Survey (NHANES) database (2009–2018), a total of 14 947 young and middle-aged respondents aged 18 to 64 were included as the research subjects. Logistic regression and restricted cubic spline (RCS) models were employed to examine the association between depressive symptoms and stroke. Cox proportional hazards model, RCS model, and Kaplan-Meier (K-M) survival curves were used to clarify the relationship between depressive symptoms and all-cause mortality risk. To verify the robustness of main findings, sensitivity analysis was conducted stratified by gender, hypertension, diabetes, hyperlipidemia, body mass index (BMI), and age. ResultsLogistic regression analysis revealed that compared with the non-depressed group, the risk of stroke in the mild depression group increased by 53.50% (OR=1.535, 95% CI: 1.147–2.053), while the moderate-to-severe depression group showed the highest risk with a 132.90% increase (OR=2.329, 95% CI: 1.733–3.129). RCS analysis indicated an approximately linear dose-response relationship between PHQ-9 score and the risk of stroke (Pfor non-linearity=0.089), with stroke risk increasing as PHQ-9 scores rose. As the PHQ-9 score increased, the risk of stroke also showed an upward trend. Cox regression analysis demonstrated that compared with the non-depressed group, the risk of all-cause mortality in the mild depression group increased by 48.80% (HR=1.488, 95% CI: 1.164–1.902), and the moderate-to-severe depression group had a 70.60% increased risk (HR=1.706, 95% CI: 1.310–2.221). RCS analysis showed a linear dose-response relationship between PHQ-9 scores and all-cause mortality risk (Pfor non-linearity=0.440). K-M curves indicated that as the severity of depressive symptoms increases, the risk of all-cause mortality gradually rises (P<0.05). Sensitivity analysis confirmed that the associations between depression symptoms and risks of stroke and all-cause mortality were not modified by gender, hypertension, diabetes, hyperlipidemia, BMI, or age, demonstrating robust findings. ConclusionAmong the young and middle-aged population, both mild and moderate-to-severe depression were associated with increased risks of stroke and all-cause mortality, with the moderate-to-severe depression group showed more pronounced risk elevations. A positive dose-response relationship was observed between depressive symptoms and these risks.
8.Analysis of the safety, economic benefit and social psychological satisfaction of day breast conserving surgery for breast cancer
Jiao ZHOU ; Xiaoxiao XIAO ; Jiabin YANG ; Yu FENG ; Huanzuo YANG ; Mengxue QIU ; Qing ZHANG ; Yang LIU ; Mingjun HUANG ; Peng LIANG ; Zhenggui DU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):160-166
Objective To investigate the safety, economic benefits and psychological effects of day breast conserving surgery for breast cancer. Methods The demographic data and clinical data of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgeries in West China Hospital of Sichuan University from March 2020 to June 2021 were retrospectively collected; the demographic data, clinical data, medical and related transportation costs, and preoperative and postoperative BREAST-Q scores of breast cancer patients undergoing day (day surgery group) and ward (ward surgery group) breast conserving surgery in West China Hospital of Sichuan University from June 2021 to June 2022 were prospectively collected. The safety, economic benefit, and psychological satisfaction of day surgery was analyzed. Results A total of 42 women with breast cancer were included in the retrospective study and 39 women with breast cancer were included in the prospective study. In both prospective and retrospective studies, the mean age of patients in both groups were <50 years. There were only statistical differences between the two groups in the aspects of hypertension (P=0.022), neoadjuvant chemotherapy (P=0.037) and postoperative pathological estrogen receptor (P=0.033) in the prospective study. In postoperative complications, there were no statistical differences in the surgical-related complications or anesthesia-related complications between the two groups in either the prospective study or the retrospective study (P>0.05). In terms of the overall cost, we found that the day surgery group was more economical than the ward surgery group in the prospective study (P=0.002). There were no statistical differences in postoperative psychosocical well-being, sexual well-being, satisfaction with breasts or chest condition between the two groups (P>0.05). Conclusion It is safe and reliable to carry out breast conserving surgery in day surgery center under strict management standards, which can save medical costs and will not cause great psychological burden to patients.
9.Evaluation of the performance of the artificial intelligence - enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula
Jihua ZHOU ; Shaowen BAI ; Liang SHI ; Jianfeng ZHANG ; Chunhong DU ; Jing SONG ; Zongya ZHANG ; Jiaqi YAN ; Andong WU ; Yi DONG ; Kun YANG
Chinese Journal of Schistosomiasis Control 2025;37(1):55-60
Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ2 = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ2 = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ2 = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ2 = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ2 = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ2 = 5.604, Padjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.
10.Analysis of detection of repeat blood donors with unqualified alanine aminotransferase
Zijian ZENG ; Fenfang LIAO ; Junmou XIE ; Zhiting WAN ; Rongsong DU ; Zhongping LI ; Haojian LIANG ; Shijie LI ; Yanli JI ; Huaqin LIANG ; Hao WANG
Chinese Journal of Blood Transfusion 2025;38(4):482-487
[Objective] To retrospectively analyze the detection results of alanine aminotransferase (ALT) unqualified repeat blood donors in Guangzhou, so as to provide evidence for further expanding the repeat blood donor pool, reducing the rate of blood discarding and improving the qualified rate of blood test. [Methods] Blood donors with unqualified ALT in Guangzhou Blood Center from January 2018 to April 2024 were selected as the research objects. The past blood donation and population characteristics were analyzed according to the number of blood donations and ALT unqualified times. [Results] Among repeat blood donors with previous ALT disqualification, 99.5% to 99.7% did not have reactive markers for transfusion-transmitted diseases (TTD), which was higher than the rate among first-time blood donors with unqualified ALT (95.8%) (P<0.05). The rate of single-item ALT disqualification in repeat blood donors was higher in males than in females (P<0.05); it also varied by age (18-25 years > 26-35 years > 36-45 years > over 45 years) (P<0.05); and by quarter (third and fourth quarters > first and second quarters) (P<0.05). The ALT unqualified rate was significantly higher whole blood donors than that of platelet donors and returning blood donors (P<0.05). The overall ALT level (51.0 U/L), individual ALT level (56.0 U/L) and individual ALT unqualified rate (66.7%) of repeat blood donors with multiple ALT disqualifications were higher than those of repeat blood donors with single-item ALT disqualifications (26.0 U/L, 38.5 U/L, and 33.3%, respectively) (P<0.05). Moreover, as the number of ALT disqualifications increased, the overall level of ALT in repeat blood donors also increased (P<0.05), and the average level of individual ALT and individual ALT unqualified ratio tended to increase. Repeat blood donors with frequent ALT disqualifications had higher ALT levels (69.0 U/L). [Conclusion] The ALT unqualified rates of repeat blood donors were mostly non-specific elevation without TTD. Repeat blood donors with multiple ALT disqualifications tend to have continuous high ALT. Moreover, and with the increase of ALT disqualifications times, the overall ALT levels the average individual ALT levels and individual ALT unqualified rates showed an increasing trend.

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