Diabetic kidney disease （DKD） is one of the main causes of chronic kidney disease. Both traditional Chinese medicine （TCM） and western medicine have their own advantages in the prevention and treatment of DKD， but there are also many difficulties. By analysis of the difficulties faced by TCM and western medicine in the differentiation and treatment of DKD， based on the theory of "miniature masses in the renal collaterals"， combined with long-term clinical practice， "internal heat leading to mass" is proposed as the core pathogenesis of DKD. Therefore， a trinity model of "disease-syndrome-symptom" for differentiation and treatment of DKD based on the core pathogenesis has been proposed. This model highlights the status of the core pathogenesis of "internal heat leading to mass" in DKD， and conducts a three-dimensional identification from the perspectives of disease， syndrome and symptom， so as to inspire clinical practice.

Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. "Internal heat leading to zheng" is the core pathogenesis of DKD, while "glucose toxicity" is transformed from subtle substances through "internal heat" and the cementation of various pathological products, which is pivotal to the transformation of diabetes to DKD. "Glucose toxicity" is characterized by deep and widespread heat, caused by various pathological factors, and its sticky nature makes it difficult to resolve, which can cause severe damage to the kidney collaterals. In the early stage of "glucose toxicity", it is yang pathogen, which can be transformed into yin pathogen in the later stage with disease progression. In clinical practice, treatment should be based on disease staging, with attention on grasping the pathogenesis of "internal heat leading to zheng" and identifying the nature of "glucose toxicity". During the diabetic period, clearing heat is the primary method, often using modified Yueju Pill and Dachaihu Decoction. In the early stage of DKD, treatment primarily focuses on clearing and penetrating latent heat to treat DKD, aiming to prevent toxic heat from transitioning from qi to blood. The approach emphasizes clearing heat and re-penetrating, detoxification, and re-clearing, often using a self-made modified Qingre Xiaozheng Decoction. In the middle and late stages of DKD, the focus shifts to clearing heat, eliminating zheng, strengthening vital qi, and dispelling turbidity, with commonly used treatments including the self-made modified Xiezhuo Xiaozheng Formula, Jingui Shenqi Pill, and Zhenwu Decoction.

Idiopathic oligoasthenospermia （IO） has been increasingly emphasized in the diagnosis and treatment of male infertility. Oxidative stress damage directly affects sperm quality and spermatogenesis， constituting a major causative factor of IO. Firstly， due to its high content of polyunsaturated fatty acids， the sperm plasma membrane is highly sensitive to reactive oxygen species （ROS）， leading to lipid peroxidation accumulation and even inducing ferroptosis. Secondly， deficient downstream key proteins in the base excision repair pathway render sperm unable to repair extensive DNA oxidative damage under oxidative stress. Simultaneously， under oxidative stress， the apoptotic pathway of sperm is cascade-activated， causing rapid loss of motility. ROS further disrupts the hypothalamic-pituitary-gonadal axis， inhibiting testosterone production and ultimately affecting spermatogenesis. Wuzi Yanzongwan，in line with traditional Chinese medicine theory of treating IO through "nourishing kidney essence and harmonizing Yin and Yang"， clinically demonstrates its ability to improve sperm morphology， count， and motility， thereby enhancing male fertility. The research on the pharmacological constituents of Wuzi Yanzongwan primarily involves establishing a characteristic spectrum of Chinese medicine to achieve quality control and exploring the pharmacology of effective components. Studies have found that its main active ingredients consist of flavonoids and phenylpropanoids. Specifically， compounds such as hyperin， acteoside， kaempferol， and schisandrin A are identified as the primary active substances and quality control components. These compounds exhibit strong antioxidant activity and have been partly applied in research related to reproductive endocrine disorders. Tripterygium glycoside is primarily used for modeling of oxidative stress-induced IO. It leads to the accumulation of various lipid peroxides in testicular tissues and concurrently compromises the body's antioxidant capacity. Mechanistic studies have found that Wuzi Yanzongwan can inhibit elevated ROS levels in IO models and enhance the body's antioxidant capacity， thereby ameliorating inflammation， suppressing cell apoptosis， promoting testosterone production， and ultimately alleviating the decline in sperm quality and spermatogenesis caused by oxidative stress.

In the differentiation and treatment of recurrent urinary tract infection （rUTI） from the perspective of the seminal orifice， it is proposed that the urinary tract belongs to the category of "seminal orifice"， and the physiological process of urination is closely related to the function of the seminal orifice. From the three dimensions of orifice body， orifice pivot and orifice spirit， the physiological relationship between seminal orifice and the function of five zang-organs （脏） is constructed， that is， lung heat， yin damage and pathogen counter-restriction lead to malnutrition of orifice body； burning heart fire and spirit disorder lead to unfavorable orifice spirit， and kidney deficiency， liver constraint and spleen stagnation lead to unfavorable orifice pivot. In the early stage of rUTI， there is usually unfavo-rable orifice pivot， for which the treatment principle should be treating the root and the branch simultaneously， consi-dering both deficiency and excess， and paying attention to the management of accompanied symptoms. Zishui Qinggan Beverage （滋水清肝饮） and Modified Shenzhuo Decoction （肾着汤加减） are often selected based on syndrome differentiation. In the middle stage， lack of nourishment of the orifice body and unfavorable orifice spirit and pivot coexist， and the treatment should be draining the orifice and unblocking strangury， commonly withmodified Qingxin Lianzi Beverage （清心莲子饮）. In the late stage， loss of nourishment of the orifice body is the main pathogenesis， and it is necessary to further nourish the orifice body to prevent recurrence， and modifed Wuzi Yanzong Pills and Erxian Decoction （五子衍宗丸合二仙汤） is often used. Furthermore， the specific medicinals should be selected targeting at the orifice body， orifice pivot， and orifice spirit， so as to nourish orifice body by dispelling external pathogens and rectify healthy qi， to drain orifice pivot by freeing emotions and minds and unblocking qi movement， and to calm orifice spirit by unblocking heart and kidney and nourishing heart spirit.

Objective To develop a high performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS)method for simultaneous determination of five flavonoids in Ganmao'an granules(GMA).Methods Chromatographic separation was achieved on a Kromasil C18 Column(150 mm×4.6 mm,5 μm,100 ?),which was eluted with methanol(A)-0.1％formic acid(B)at the flow rate of 1.0 ml/min.The gradient condition was as follows:0-20 min,35％A,and 20-40 min,45％A.The column temperature was 25 ℃.Analytes were detected using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source in the negative ion scanning.The multiple reaction monitoring mode was used for qualitative analysis.For each flavonoid,two precursor ion/product ion transitions were chosen:lutin m/z 609.1→300.1,hyperin and isoquercitrin m/z 463.0→300.1,quercetin m/z 301.0→151.0,luteolin m/z 285.0→132.9.Results Five flavonoids showed the good relationships within their own concentration ranges(correlation coefficient r>0.999 1),whose average recoveries were in the range of 100.63％-102.81％with RSDs of 0.67％-2.07％.The content results of rutin,hyperoside,isoquercetin,quercetin,and luteolin in 10 batches of GMA were 32.23-479.83,0.291-1.825,11.44-20.54,6.32-18.41,3.46-6.51 μg/g,respectively.Conclusion The results indicated that the developed method was sensitive,accurate and could provide excellent specificity for simultaneous determination of five flavonoids in GMA.

Objective:To analyze and summarize the oncological outcomes after laparoscopic radical trachelectomy (LRT) for early stage cervical cancer.Methods:The clinical data and follow-up results of 148 patients with early stage cervical cancer who underwent LRT in Renji Hospital, School of Medicine, Shanghai Jiao Tong University from July 2014 to June 2023 were collected, while tumor outcomes and postoperative pregnancy were analyzed retrospectively.Results:(1) General situation: the median age of 148 patients with LRT was 33 years (range: 19-42 years). Pathological type: 111 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, 1 case of adenosquamous carcinoma. International Federation of Gynecology and Obstetrics (2018) stage: 17 cases of stage Ⅰa1 with lympho-vascular space invasion, 25 cases of stage Ⅰa2, 102 cases of stage Ⅰb1, and 4 cases of stage Ⅰb2. (2) Tumor outcomes: 148 patients were followed up regularly after LRT, and the median follow-up time was 59 months (range: 2-104 months). During the follow-up period, 5 cases of tumor recurred (including 1 death), and the median recurrence time was 10 months (range: 4-33 months). Among them, there were 3 cases of pelvic metastasis, 1 case of distant metastasis, and 1 case of both pelvic and distant metastasis. Both 3-year and 5-year disease-free survival rates of 148 patients were 94.5%, and the 5-year overall survival rate was 98.9%. (3) Postoperative pregnancy: among 148 patients with LRT, 67 patients had pregnancy requirements, followed up for 1 year, and 20 of them were pregnant, with a pregnancy rate of 29.9% (20/67). Among the 20 pregnant patients, 2 cases early abortion, 1 case mid-term abortion, and 17 cases gave birth (including 4 cases of premature birth and 13 cases of full-term birth).Conclusion:Under the condition of strict control of surgical indications, guaranteed surgical scope and tumor-free operation, LRT in patients with early cervical cancer has a good outcome.

OBJECTIVE To study the pharmacological substance basis of Shaoyao gancao decoction for relieving acute and chronic pain. METHODS The antispasmodic effect of Shaoyao gancao decoction， ethyl acetate extract of Shaoyao gancao decoction and its effluent part of macroporous resin and 90% ethanol elution part of macroporous resin （the concentration of 4 drugs was 13.44 g/mL according to crude drug） was observed by in vitro small intestine tension test in rats. The acetic acid writhing test was conducted in mice to evaluate the analgesic effects of macroporous resin efflux site and macroporous resin 90% ethanol elution site （the dosage of 2.4 g/kg according to crude drug）. The levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL- 1β）， prostaglandin E2 （PGE2） and cyclooxygenase-2 （COX-2） in serum of mice were detected. The serum prototype and metabolites of mice after intragastric administration of macroporous resin 90% ethanol elution site were identified by high performance liquid chromatogre-time-of-flight mass spectrometry. RESULTS In vitro experiment showed that 90% ethanol eluting part of macroporous resin represented the best antispasmodic effect， and the inhibitory rate of small intestine tension was significantly higher than macroporous resin efflux site of Shaoyao gancao decoction （P＜0.05） without statistical significance， compared with Shaoyao gancao decoction （P＞0.05）. In the acetic acid writhing experiment， compared with model group， the writhing times of mice in the macroporous resin 90% ethanol elution part group were reduced significantly （P＜0.05）， the writhing latency was prolonged significantly （P＜0.05）， and the levels of COX-2， IL-1β， PGE2 and TNF-α in serum were decreased significantly （P＜0.05）. Ten kinds of protoproducts including paeoniflorin and glycyrrhizic acid were identified from serum of mice， and twenty-two kinds of metabolites including hydroxylated glycyrrhizin and glucosylated liquiritin were identified. CONCLUSIONS The effective part of Shaoyao gancao decoction for relieving acute and chronic pain is 90% ethanol elution part prepared by macroporous resin from the ethyl acetate extract. Ten components， including glycyrrhetinic acid and paeoniflorin， may be the basis of its pharmacological substances.

WANG Qishi put forward the theory of "yang deficiency with three lackings， controlled by the spleen" in Lixu Yuanjian （《理虚元鉴》）， which regarded that yang deficiency can lead to consumptive diseases with changes of lacking essence， lacking qi， and lacking fire， so the treatment should start from the spleen to restore the middle yang urgently. This article summarised the experience of treating type 4 cardiorenal syndrome based on the theory of "yang deficiency with three lackings， controlled by the spleen"， and proposed that lacking essence is the beginning of the onset of type 4 cardiorenal syndrome， lacking qi is the gradual development of the disease， and lacking fire is the changes of the disease， and ultimately resulted in the complex situation of kidney and qi deficiency， and edema due to yang deficiency， combined with syndromes variation. In the clinical evidence， in the stage of lacking fire， therapies should warm the middle and strengthen the spleen in order to rescue the middle yang， prescribed with modified Baoyuan Decoction （保元汤） plus Lizhong Decoction （理中汤）； in the stage of lacking qi， prescriptions can add Taoren （Juglans regia）， Tubiechong （Eupolyphaga sinensis）， Fuling （Smilax glabra）， Guizhi （Neolitsea cassia） to activate blood and drain water to transport and restore the center qi； in the stage of lacking essence， prescriptions can add Gouqizi （Lycium barbarum）， Tusizi （Cuscuta chinensis）， Duzhong （Eucommia ulmoides）， Bajitian （Gynochthodes officinalis） to supplement deficiency and resolve masses to consolidate the root and supplement essence.

Objective To investigate the regulatory mechanism of apurnic/apyrimidinic endonuclease 1(APE1)in the transformation of chronic intestinal inflammation to colitis-associated colorectal cancer(CAC).Methods C64S mutant(APE1C64S)mice and APE1 wild type(APE1WT)mice were randomly divided into experimental group and control group.In vivo CAC model was established by azoxymethane(AOM)and dextran sulfate sodium salt(DSS)solution.Immunohistochemistry(IHC)and multiple IHC(mIHC)assays were used to observe the expression of APE1 and immune cell infiltration in colon tissues of each group.A mouse colon cancer cell line MC38 with stable knockdown of APE1 was constructed by lentivirus transfection,and subcutaneous tumor bearing experiments were performed in APE1WT and APE1C64S mice to confirm that tumor cell-derived APE1 caused immunosuppressive tumor microenvironment.The expression of APE1 and CXCL1[chemokine(C-X-C motif)ligand 1]and the infiltration of immune cells in tumor-bearing specimens were analyzed by IHC and mIHC assays.The tumor specimens of a 28-year-old female patient with CAC from Army Medical Center of PLA were analyzed for the expression of APE1 and CXCL1 and the infiltration of immune cells in the tumor and adjacent inflammatory tissues by IHC and mIHC assays.Results Compared with the control group and APE1WT erperimental group,APE1C64S erperimental group had significantly reduced disease activity index and tumor formation,polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs)infiltration,and CD4+and CD8+T cells(P＜0.05).No significant differences were observed in tumor growth and immune cells between APE1WT and APE 1C64S mice bearing subcutaneous tumors.However,in the tumor-bearing experiment using tumor cells with knockdown of APE1,the tumor growth was significantly lower and the number of infiltrated PMN-MDSCs was reduced,while those of CD4+and CD8+T cells were significantly increased(P＜0.05).Furthermore,high expression of APE1 and increased infiltration of PMN-MDSCs were found in the tumor tissues of the young CAC patient,and CD8+T cells were significantly reduced in the tumor tissues compared with the inflammatory tissues(P＜0.05).Conclusion APE1-redox in tumor cells can promote the infiltration of PMN-MDSCs and reduce the number of T cells,thereby forming an immunosuppressive tumor microenvironment and mediating the occurrence and development of CAC.

Objective To explore the regulatory role of hederagenin(HG)on glutamate(Glu)-in-duced ferroptosis and corresponding inflammatory responses in mouse hippocampal neuron HT22 cells and investigate its potential mechanisms.Methods HT22 cells were randomly divided into control,Glu and HG groups(n=3).The cells of the control group received no treatment,the cells of the Glu group were treated with 35 mmol/L Glu for 24 h to establish a cellular model of ferroptosis in Alzheimer's disease,and the cells of the HG group were treated with 0.5 μmol/L HG and 35 mmol/L Glu for 24 h simultaneously.FerroOrange fluorescent probe was used to de-tect intracellular Fe2+.The production of reactive oxygen species(ROS),mitochondrial membrane potential,and levels of inflammatory factors TNF-α,IL-1β and IL-6 in the cells were assessed.Finally,the expression of the key regulator of iron death,glutathione peroxidase 4(GPX4)was measured.Results Compared to the control group,the levels of intracellular Fe2+,ROS,TNF-α,IL-1β,and IL-6 were significantly elevated,while the mitochondrial membrane potential was obvi-ously reduced in the Glu group(P＜0.05,P＜0.01).The HG group had significantly decreased Fe2+,ROS,TNF-α,IL-1β,and IL-6 and enhanced mitochondrial membrane potential than the Glu group(P＜0.05,P＜0.01).The GPX4 expression was significantly lower in the Glu group than the control group(1.00±0.02 vs 0.46±0.04,P＜0.01),and was notably higher in the 0.5 and 1.0 μmol/L HG groups when compared to the Glu group(0.64±0.03 and 0.59±0.05 vs 0.46±0.04,P＜0.01).Conclusion HG inhibits ferroptosis by regulating GPX4 expression,and thereby effec-tively alleviates the inflammatory response.