1.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P0.01) and increases in number of platform crossings (P0.05), alternation rate (P0.01), number of entries into the new arm (P0.05), preference index (P0.01), and discrimination index (P0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P0.05) and elevated levels of ACh and DA (P0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
2.Banxia Xiexin Tang Ameliorates Cognitive Dysfunction in Rat Model of Vascular Dementia via AGE/RAGE Pathway
Shuzhi LIANG ; Zhongmin ZHAO ; Suyu HOU ; Dandan LUO ; Yan ZHANG ; Xijian LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(3):10-21
ObjectiveTo explore the mechanism by which Banxia Xiexin Tang (BXT) regulates the advanced glycation end products (AGE)/receptor for advanced glycation end products (RAGE) signaling pathway to reduce neuroinflammatory responses and ameliorate cognitive dysfunction in the rat model of vascular dementia (VD). MethodsThe components of BXT were detected by ultra performance liquid chromatography-quadrupole -orbitrap-tandem mass spectrometry(UPLC-Q-Orbitrap-MS/MS), and the core components and key action pathways were screened out by network pharmacology and molecular docking. Sixty SPF-grade male SD rats were randomly allocated into the sham and modeling groups by the random number table method. The VD model was replicated by the modified bilateral occlusion of the common carotid arteries (2-VO) method. The successfully modeled rats were randomly allocated into the model, low-, medium-, and high-dose (3.748 5, 7.497, 14.994 g·kg-1) BXT (BXT-L, BXT-M, and BXT-H), and nimodipine (NMP, 0.002 7 g·kg-1) groups according to the random number table method. The rats in the drug intervention groups were administrated with corresponding drugs by gavage, and the sham and model groups received the same amount of normal saline for 14 consecutive days. The Morris water maze, Y-maze, and new object recognition experiments were conducted to evaluate the cognitive dysfunction of rats. Hematoxylin-eosin (HE) staining was used to evaluate the histopathological changes of the hippocampal tissue in rats. The mRNA levels of AGE, RAGE, and phosphorylated nuclear factor-kappa B p65 (p-NF-κB p65) in the hippocampal tissue of rats were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). The expression of related proteins in the AGE/RAGE pathway in the hippocampal tissue of rats was determined by Western blot and immunohistochemistry (IHC). The levels of neurotransmitters and inflammatory mediators in the rat serum were measured by enzyme-linked immunosorbent assay (ELISA). ResultsThe chemical components of BXT were detected by UPLC-Q-Orbitrap-MS/MS. Network pharmacology and molecular docking identified the AGE/RAGE pathway as the key pathway. The results of the water maze, Y maze, and novel object recognition tests showed that compared with the sham group, the model group demonstrated prolonged successful latency and decreases in number of platform crossings, alternation rate, number of entries into the new arm, preference index, and discrimination index (P<0.01). Compared with the model group, the BXT-H and BXT-M groups showed shortened successful latency (P<0.01) and increases in number of platform crossings (P<0.05), alternation rate (P<0.01), number of entries into the new arm (P<0.05), preference index (P<0.01), and discrimination index (P<0.01). HE results showed that compared with the sham group, the cells of model rats were loosely and disorderly arranged, and the nuclei were condensed. Compared with the model group, the pathological changes of the hippocampus in the BXT group were mitigated. Real-time PCR results showed that compared with the sham group, the model group presented up-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 in the hippocampus (P<0.01), and compared with the model group, the BXT-H and BXT-M groups showcased down-regulated mRNA levels of AGE, RAGE, and p-NF-κB p65 (P<0.01). Western blot results showed that compared with the sham group, the model group presented up-regulated expression of AGE, RAGE, p-NF-κB p65, and tumor necrosis factor-α (TNF-α) (P<0.05), and compared with the model group, the BXT-H group presented down-regulated expression of AGE, RAGE, p-NF-κB p65, and TNF-α (P<0.05). IHC results showed that compared with the sham group, the model group had increased expression of RAGE (P<0.01), and compared with the model group, the BXT-H and BXT-M groups had reduced expression of RAGE (P<0.01). ELISA results showed that compared with the sham group, the model group exhibited elevated levels of TNF-α and Interleukin-1β (IL-1β) and declined levels of acetylcholine (ACh) and dopamine (DA) in the serum (P<0.01). Compared with the model group, the BXT-L, BXT-M, and BXT-H groups showed lowered levels of TNF-α and IL-1β in the serum (P<0.05) and elevated levels of ACh and DA (P<0.05). ConclusionBXT may ameliorate cognitive dysfunction in the rat model of VD by down-regulating the AGE/RAGE signaling pathway, reducing neuroinflammatory responses, and regulating neurotransmitter levels.
3.Fabrication and evaluation of an inositol hexaphosphate-zinc hydrogel with dual capabilities of self-mineralization and osteoinduction
LIU Mingyi ; MIAO Xiaoyu ; CAI Yunfan ; WANG Yan ; SUN Xiaotang ; KANG Jingrui ; ZHAO Yao ; NIU Lina
Journal of Prevention and Treatment for Stomatological Diseases 2026;34(1):29-40
Objective:
To fabricate a hydrogel loaded with inositol hexaphosphate-zinc and preliminarily evaluate its performance in self-mineralization and osteoinduction, thereby providing a theoretical basis for the development of bone regeneration materials.
Methods:
The hydrogel framework (designated DF0) was formed by copolymerizing methacryloyloxyethyltrimethylammonium chloride and four-armed poly(ethylene glycol) acrylate, followed by sequentially loading inositol hexaphosphate anions via electrostatic interaction and zinc ions via chelation. The hydrogel loaded only with inositol hexaphosphate anions was named DF1, while the co-loaded hydrogel was named DF2. The self-mineralization efficacy of the DF0 , DF1 and DF2 hydrogels was characterized using scanning electron microscopy, transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS), and selected area electron diffraction (SAED). The biocompatibility was assessed via live/dead cell staining and a CCK-8 assay. The osteoinductive capacity of the DF0 , DF1 and DF2 hydrogels on MC3T3-E1 cells was assessed via alkaline phosphatase (ALP) and Alizarin Red S (ARS) staining. In the aforementioned cell experiments, cells cultured in standard medium served as the control group
Results:
The DF0, DF1, and DF2 hydrogels were successfully synthesized. Notably, DF1 and DF2 exhibited distinct self-mineralization within 6 days. Results from TEM, EDS, and SAED confirmed that the mineralization products were amorphous calcium phosphate in group DF1, and amorphous calciumzinc phosphate in group DF2. Biocompatibility tests revealed that none of the hydrogels (DF0, DF1, and DF2) adversely affected cell viability or proliferation. In osteogenic induction experiments, both ALP and ARS staining were intensified in the DF1 and DF2 groups, with the most profound staining observed in the DF2 group.
Conclusion
The developed inositol hexaphosphate-zinc hydrogel (DF2) demonstrates the dual capacity to generate calcium-phosphate compounds through self-mineralization while exhibiting excellent osteoinductive properties. This biocompatible, dual-promoting osteogenic hydrogel presents a novel strategy for bone regeneration.
4.Discussion on the Application of Warm-Yang Method in Polycystic Ovary Syndrome Infertility
Pengxuan YAN ; Haiyan ZHANG ; Yukun ZHAO ; Yabei GAO ; Kun LI ; Jingchun ZHANG ; Yuping ZHAO ; Zixiao WEI
Journal of Traditional Chinese Medicine 2025;66(3):312-316
It is believed that there is a pathogenesis of yang deficiency in polycystic ovary syndrome (PCOS) infertility, and it is concluded that warm-yang method has a better effect in improving endometrial abnormality, enhancing the quality of follicles, correcting endocrine disorders, and resolving or alleviating clinical symptoms in PCOS infertility. Based on Yanghe Decoction (阳和汤), a representative traditional Chinese medicine decoction for warming yang, Yanghe Xiaonang Decoction (阳和消囊汤) was formulated, combining with warm medicinals according to symptoms, and aerobic exercise was also advocated to help generate and develop yang qi, in order to provide ideas for clinical treatments.
5.Hepatitis E virus infection among blood donors in Zhengzhou
Hongna ZHAO ; Yueguang WEI ; Lumin YAN ; Tiantian TU ; Shumin WANG ; Yihui WEI ; Yifang WANG ; Lei ZHAO ; Mingjun CHEN
Chinese Journal of Blood Transfusion 2025;38(1):13-18
[Objective] To analyze the infection status of hepatitis E virus (HEV) among blood donors in Zhengzhou, so as to provide data support for formulating local blood screening strategies. [Methods] Random samples from blood donors from January to December 2022 were tested for HEV RNA using PCR technology. Reactive samples were sequenced for gene analysis, and the donors were followed up. [Results] Among 21 311 samples, 3(0.14‰) were reactive for HEV RNA, all of whom were male. Genetic sequencing results revealed that one strong positive sample was genotype 4, while sequencing failed for the other two due to low viral load. A follow-up of 25 strong positive donors showed that ALT significantly increased on day 7 after donation, anti-HEV IgM and anti-HEV IgG turned positive. On day 21, ALT returned to normal, and on day 35, HEV RNA turned negative. Notably, anti-HEV IgM and anti-HEV IgG persisted until day 482. [Conclusion] There is HEV infection among blood donors in Zhengzhou, and it is necessary to expand the screening scope to comprehensively explore the prevalence and genotype distribution of HEV among blood donors.
6.Quality evaluation of Jingtian granule based on fingerprint combined with chemical pattern recognition
Wei ZHAO ; Shuhe CHEN ; Bin YAN ; Qiongfang ZHENG ; Weixin ZHANG ; Yuanming BA
China Pharmacy 2025;36(3):300-305
OBJECTIVE To establish the ultra-high performance liquid chromatography (UPLC) fingerprint of Jingtian granule, and to evaluate its quality by chemical pattern recognition. METHODS Luna® Omega Polar C18 column (150 mm×2.1 mm, 1.6 μm) was used as the chromatographic column, and acetonitrile-0.2% phosphoric acid solution was used as the mobile phase for gradient elution. The flow rate was 0.2 mL/min, the column temperature was 30 ℃, and the detection wavelength was 265 nm. With peak 16 as the reference peak, the UPLC fingerprint of Jingtian granule was established by the Similarity Evaluation System of Chromatographic Fingerprint of Traditional Chinese Medicine (2012 edition). The common peaks were identified, the similarity evaluation was carried out, and the ownership of each common peak was confirmed. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) in chemical pattern recognition methods were used to classify 13 batches of samples (S1- S13), and orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to identify the key components of the differences between different batches of samples. RESULTS RSDs of precision, repeatability and stability of the UPLC method were not more than 4.4%. A total of 25 common peaks were identified in the fingerprints of 13 batches of Jingtian granules. By comparing with the reference substance fingerprint, 10 common peaks were identified, namely peak 3 (hydroxymethyl-2-furaldehyde), peak 5 (salidroside), peak 8(chlorogenic acid), peak 15 (cinnamic acid), peak 19 (aloe-emodin), peak 20 (ammonium glycyrrhizinate), peak 21 (rhein), peak 23 (emodin), peak 24 (glycyrrhetinic acid), peak 25 (chrysophanol). The similarities of fingerprints of 13 batches of samples were 0.955-0.996. The results of HCA showed that 13 batches of samples could be divided into three categories, among which samples S1, S5, S7, S11-S13 were clustered in one category, S4 and S6 were clustered in one category, S2, S3 and S8-S10 were clustered in one category. PCA results showed that the cumulative variance contribution rate of principal components 1-7 was 92.666%. OPLS-DA further identified 13 differential components, which were mainly derived from Polygonati Rhizoma with wine steaming, Rhodiolae Crenulatae Radix Et Rhizoma, prepared Rhei Radix Et Rhizoma and Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle. CONCLUSIONS The established UPLC fingerprint of Jingtian granule is simple, stable and reproducible. Combined with the chemical pattern recognition method, it can effectively reveal the overall quality difference between different batches of Jingtian granule. The quality of Polygonati Rhizoma with wine steaming, Rhodiolae Crenulatae Radix Et Rhizoma, prepared Rhei Radix Et Rhizoma, Dioscoreae Nipponicae Rhizoma, Polyporus, Cinnamomi Ramulus, Glycyrrhizae Radix Et Rhizome Praeparata Cum Melle is the key to the overall quality of Jingtian granule.
7.Palpitations, Shortness of Breath, Weakness in Limbs, Edema, and Dyspnea: A Rare Inflammatory Myopathy with Positive Aniti-mitochondrial Antibodies and Cardiac Involvement
Chunsu LIANG ; Xuchang ZHANG ; Ning ZHANG ; Lin KANG ; Xiaohong LIU ; Jiaqi YU ; Yingxian LIU ; Lin QIAO ; Yanli YANG ; Xiaoyi ZHAO ; Ruijie ZHAO ; Na NIU ; Xuelian YAN
Medical Journal of Peking Union Medical College Hospital 2025;16(1):248-255
This article presents a case study of a patient who visited the Geriatric Department of Peking Union Medical College Hospital due to "palpitations, shortness of breath for more than 2 years, limb weakness for 6 months, edema, and nocturnal dyspnea for 2 months". The patient exhibited decreased muscle strength in the limbs and involvement of swallowing and respiratory muscles, alongside complications of heart failure and various arrhythmias which were predominantly atrial. Laboratory tests revealed the presence of multiple autoantibodies and notably anti-mitochondrial antibodies. Following a comprehensive multidisciplinary evaluation, the patient was diagnosed with anti-mitochondrial antibody-associated inflammatory myopathy. Treatment involved a combination of glucocorticoids and immunosuppressants, along with resistance exercises for muscle strength and rehabilitation training for lung function, resulting in significant improvement of clinical symptoms. The case underscores the importance of collaborative multidisciplinary approaches in diagnosing and treating rare diseases in elderly patients, where careful consideration of clinical manifestations and subtle abnormal clinical data can lead to effective interventions.
8.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
9.Trends in incidence and mortality of lung cancer in Huangpu District from 2002 to 2019
QIU Fengqian ; ZHAO Junfeng ; CHEN Weihua ; DU Juan ; JI Yunfang ; GAO Shuna ; MENG Jie ; HE Lihua ; CHEN Bo ; ZHANG Yan
Journal of Preventive Medicine 2025;37(2):143-147
Objective:
To investigate the trends in incidence and mortality of lung cancer in Huangpu District, Shanghai Municipality from 2002 to 2019, so as to provide the evidence for formulating lung cancer prevention and control measures.
Methods:
Data of lung cancer incidence and mortality among residents in Huangpu District from 2002 to 2019 were collected through the Shanghai Cancer Registration and Reporting Management System. The crude incidence and mortality of lung cancer was calculated, and standardized by the data from the Chinese Fifth National Population Census in 2000 (Chinese-standardized rate) and the Segi's world standard population in 1960 (world-standardized rate). The trends in incidence and mortality of lung cancer among residents by age and gender were evaluated using annual percent change (APC).
Results:
A total of 12 965 cases of lung cancer were reported in Huangpu District from 2002 to 2019, and the crude incidence rate was 80.66/105, the Chinese-standardized incidence rate was 34.54/105, and the world-standardized incidence rate was 31.30/105, all showing upward trends (APC=4.588%, 2.933% and 3.247%, all P<0.05). A total of 10 102 deaths of lung cancer were reported, and the crude mortality rate was 62.30/105, showing an upward trend (APC=0.959%, P<0.05); the Chinese-standardized mortality was 25.93/105, and the world-standardized mortality was 22.05/105, both showing downward trends (APC=-1.282% and -1.263%, both P<0.05). The crude incidence and mortality rates of lung cancer in males were higher than those in females (101.39/105 vs. 60.52/105, 85.45/105 vs. 39.87/105, both P<0.05). The crude incidence and mortality rates of lung cancer showed upward trends with age (both P<0.05), reaching their peaks in the age groups of 80-<85 years (341.37/105) and 85 years or above (355.97/105), respectively.
Conclusions
The incidence of lung cancer showed an upward trend, while the mortality showed a downward trend in Huangpu District from 2002 to 2019. Elderly men were the high-risk group for lung cancer incidence and mortality.
10.Professor LIU Jinmin's Clinical Experience in Treating Epilepsy Based on the Method of Closing Yangming and Regaining Vital Activity
Lin ZOU ; Tianye SUN ; Mingyuan YAN ; Mi ZHAGN ; Shuai ZHAO ; Kaiyue WANG ; Lili LI ;
Journal of Traditional Chinese Medicine 2025;66(4):344-348
To summarize the clinical experience of Professor LIU Jinmin in treatment for epilepsy. It is believed that main pathogenesis of epilepsy is yangming failure to close and vital activity loss control, so a therapeutic approach focused on restoring the closure of yangming and regaining vital activity was proposed for the treatment of epilepsy. For excess syndrome, the treatment focuses on draining excess and descending qi, promoting purgation and restoring spirit. When yangming dryness-heat predominates, the approach involves unblock the bowels and regulating the spirit, descending qi and reducing fire, with modified Chengqi Decoction (承气汤) as prescription; when yangming phlegm-fire predominates, the treatment focuses on clearing heat and resolving phlegm, calming mind and suppressing fright, with modified Qingxin Wendan Decoction (清心温胆汤) as prescription; when yangming blood stasis predominates, the approach involves breaking up blood stasis and promoting purgation, eliminating stasis and awakening the mind, with Taoren Chengqi Decoction (桃核承气汤) as prescription. For deficiency syndrome, the treatment emphasizes tonifying deficiency and raising qi, strengthening the stomach and nourishing the spirit. When center qi deficiency and sinking of clear qi of the nutrients from food, the approach involves replenishing and uplifting qi while nourishing vital activity, with modified Liujunzi Decoction (六君子汤) as prescription; when yin deficiency and fluid consumption, the treatment focuses on nourishing stomach and tonifying yin, promoting fluid production and calming the spirit, with modified Maimendong Decoction (麦门冬汤) combined with Yiwei Decoction (益胃汤) as prescriptions. In clinical situations of deficiency-excess complex, it is essential to distinguish the primary condition from the secondary, applying both supplementing and draining methods flexibly to achieve optimal treatment.


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