Microvascular diseases （MVD） can affect multiple systems in the body and are important factors in the occurrence and development of cardiovascular， cerebrovascular， renal， and metabolic diseases， as well as the aging process. It is proposed that the key pathogenesis of MVD is "cold constraint in sanjiao （三焦）". Based on the theory of cold pathogen， and by integrating the common and local pathologies of sanjiao， a treatment principle of promoting blood circulation and warming is established. A basic prescription for promoting blood circulation and warming is formulated， with modifications based on the specific pathogenesis of the upper， middle， and lower jiao （焦）. For the upper jiao， cold constraint primarily involves the failure of the clear yang to rise and qi and blood stagnation， for which treatment should focus on diffusing and unblocking the heart and the lung， opening constraint and vibrating yang， commonly adding Shengxian Decoction （升陷汤） for warming and dispersing to assist in diffusion and dissipation， and using Guizhi Decoction （桂枝汤）-series formulas to harmonize ying-wei （营卫） and open the striae and interstices； both formulas can invigorate yang qi. For the middle jiao， cold constraint primarily involves the dysfunction of the central yang and internal accumulation of turbid pathogen， for which treatment should focus on harmonizing the spleen and stomach， warming and reinforcing yang； formulas such as Sini Powder （四逆散）， Zhishi Xiaopi Pill （枳实消痞丸）， and Banxia Xiexin Decoction （半夏泻心汤） can be used to restore qi flow， promote digestion， and balance cold and heat； Shengyang Yiwei Decoction （升阳益胃汤） can further enhance raising the clear and directing the turbid downward， expelling cold and removing dampness. For the lower jiao， cold constraint primarily involves damage to the original yang and dysfunction of qi transformation， for which the treatment should focus on tonifying original qi and reinforcing the foundation， as well as promoting diuresis and supporting yang； depending on the degree of deficiency and the presence of internal water accumulation， formulas like Jingui Shenqi Pill （金匮肾气丸）， Fuzi Decoction （附子汤）， and Zhenwu Decoction （真武汤） can be used. Based on the theory of cold constraint， the principle of promoting blood circulation and warming method runs through the differentiation and treatment of MVD. By further incorporating the pathological characteristics of sanjiao， flexible treatment strategies can be developed， which helps deepen the understanding of the disease's etiology and pathogenesis， while broadening clinical diagnostic and therapeutic approaches.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

ObjectiveTo investigate the effects of Qizhujianwei granules （QZJW） on abnormal proliferation and malignant transformation of gastric mucosal cells in rats with gastric intraepithelial neoplasia （GIN） and to explore the related mechanisms. MethodsA total of 80 SPF male Wistar rats were used. A GIN rat model was established using a four-factor comprehensive method consisting of methylnitronitrosoguanidine （MNNG）， ranitidine， irregular feeding patterns， and sodium salicylate. Except for the normal group， after successful modeling， the rats were randomly divided according to body weight into a model group， a Moluodan group （0.55 g·kg^-1）， and a QZJW group （7.34 g·kg^-1）， with 12 rats in each group. All groups were treated for 8 weeks. The general characteristics of the rats and morphological changes of the gastric mucosa were observed. Histopathological changes of the gastric mucosa were examined by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum levels of pepsinogenⅠ （PGⅠ）， pepsinogenⅡ （PGⅡ）， and gastrin （G-17）， as well as the expression level of transforming growth factor-β₁ （TGF-β₁） in gastric mucosal tissue， and the PGⅠ/PGⅡ ratio was calculated. Immunohistochemistry （IHC） was used to detect the localization and expression levels of proliferating cell nuclear antigen （Ki-67） and Vimentin in gastric mucosal tissue. Western blot analysis was used to determine the protein expression levels of Wnt family member 3A （Wnt3a）， β-catenin， CyclinD₁， proto-oncogene Cmyc， transforming growth factor-β receptor Ⅰ （TGFβRⅠ）， intracellular signaling transducers Smad2/3， phosphorylated （p）-Smad2/3， twist family transcription factor （Twist1）， and Vimentin in gastric mucosal tissue. ResultsCompared with the normal group， the model group showed characteristic changes including dim eyes， pale ears and claws， dark-red tongue， and reduced luster of the tail. The gastric mucosa appeared pale， with surface congestion and erosion. The gastric mucosal glands were disordered， the nuclear-to-cytoplasmic ratio increased， and local tumor cells were observed. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly decreased （P<0.01）， while the level of G-17 was significantly increased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly increased （P<0.05， P<0.01）， whereas the ratio of p-Smad2/3 to Smad2/3 was significantly decreased （P<0.05）. Compared with the model group， the general characteristics and gastric mucosal conditions of rats in the Moluodan group and the QZJW group were improved. HE staining showed that QZJW could effectively block the malignant progression of GIN. Serum PGⅠ and PGⅡ levels and the PGⅠ/PGⅡ ratio were significantly increased （P<0.05， P<0.01）， while the level of G-17 was significantly decreased （P<0.01）. The protein expression levels of Ki-67， Wnt3a， β-catenin， CyclinD₁， Cmyc， TGF-β₁， TGFβRⅠ， Smad2/3， Twist1， and Vimentin in gastric mucosal tissue were significantly decreased （P<0.05， P<0.01）. ConclusionQZJW have a therapeutic effect on rats with GIN. The mechanism may involve inhibition of the Wnt/β-catenin signaling pathway to regulate the cell cycle and suppress abnormal cell proliferation. Meanwhile， it may inhibit epithelial-mesenchymal transition by suppressing the TGF-β₁/Smad/Twist1 signaling pathway， thereby blocking the malignant progression of GIN.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

Objective To explore the clinical experience of Professor Wang Yan'gang in treating gastroesophageal reflux disease(GERD)using data mining methods.Methods SPSS 23.0 was used to statistically analyze the frequency,properties,flavors,and meridian tropism of Chinese herbal medicines in the prescriptions of effective GERD cases treated by Professor Wang Yan'gang in outpatient clinics from January 2020 to December 2022.Cluster analysis,factor analysis,and association rule analysis were performed on the relevant drugs.Results A total of 294 outpatient prescriptions for the treatment of GERD were collected,including 174 Chinese herbal medicines.The top 10 frequently-used drugs were Sepiae Endoconcha(Haipiaoxiao),Fritillariae Thunbergii Bulbus(Zhebeimu),Scutellariae Radix(Huangqin),Coptidis Rhizoma(Huanglian),Pinelliae Rhizoma Praeparatum Cum Alumine(Qingbanxia),Arecae Semen Tostum(Chaobinglang),Artemisiae Scopariae Herba(Yinchen),Gypsum Fibrosum(Shigao),Aurantii Fructus Immaturus(Zhishi),and Magnoliae Officinalis Cortex(Houpo).After cluster analysis,factor analysis,and association rule analysis,16 commonly-used herb pairs,such as Huangqin-Huanglian,Citri Reticulatae Pericarpium(Chenpi)-Zhuru(Bambusae Caulis in Taenia),Haipiaoxiao-Zhebeimu,Shichangpu(Acori Tatarinowii Rhizoma)-Yujin(Curcumae Radix),and Zhishi-Houpo were identified,and 9 herb groups such as"Huangqin,Huanglian,Yinchen"and"Chenpi,Zhuru,Qingbanxia"were obtained.Factor analysis was performed on 22 drugs with a usage frequency more than 110 times,and then 6 common factors were extracted after principal component analysis.Conclusion In differentiating and treating GERD,Professor Wang Yan'gang suggests that stagnated heat injuring yin should be taken as the core pathogenesis,and therapy of clearing heat and nourishing yin should be used as the core treatment method.Additionally,auxiliary methods such as soothing the throat,regulating the liver and stomach,and nourishing the heart and spirit can be adopted according to the accompanying symptoms during the disease progression.

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4⁺ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Objective:To compare the efficacy of pars plana vitrectomy (PPV) combined with human amniotic membrane (hAM) plugging technique or internal limiting membrane (ILM) flap insertion technique for high myopia macular hole retinal detachment (MHRD).Methods:A non-randomized controlled clinical study was performed.Sixteen eyes of 15 patients with high myopia MHRD treated in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine from July 2020 to August 2021 were included.All patients underwent PPV and were divided into hAM plug group (7 eyes of 7 patients) and the ILM insertion group (9 eyes of 8 patients) based on the different plugging materials.The best corrected visual acuity (BCVA) and intraocular pressure were measured before surgery and at 1 week, 1, 3, and 6 months postoperative, respectively.Slit-lamp microscopy combined with lenses, scanning laser ophthalmoscope and optical coherence tomography (OCT) were used to examine the fundus, the macular hole closure and retinal reposition.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine (No.SH9H-2021-T322-2). Written informed consent was obtained from each subject.Results:The retinal reattachment was achieved in 6 eyes in the hAM plug group and all 9 eyes in the ILM insertion group after initial surgery.The macular hole closure was observed in 5 eyes in the hAM plug group and 8 eyes in the ILM insertion group after initial surgery, and there was no statistical difference in the macular hole closure rate between the two groups ( P>0.05). There were significant differences in the overall comparison of BCVA between the two groups over time ( Ftime=4.420, P<0.05). Postoperative BCVA at different time points was better than preoperative BCVA in each group, but the differences were not significant (all at P>0.05). There was no significant difference in the overall comparison of BCVA between the two groups ( Fgroup=0.183, P>0.05). Two eyes in the hAM plug group and 4 eyes in the ILM insertion group developed transient ocular hypertension, which returned to normal after 1 week of treatment. Conclusions:Both PPV combined with hAM plugging technique and ILM insertion technique are safe and effective for the treatment of MHRD in high myopia.The hAM plugging technique can not only achieve anatomical reduction but also functional recovery of the retina even in complicated fundus conditions.

Objective To investigate the presence of pepsin and trypsin in the middle ear effusion of children with acute suppurative otitis media(ASOM).Methods Middle ear effusion samples were collected from 71 children with ASOM at Children's Hospital of Xuzhou.According to the characteristics of the middle ear effusions,the effu-sion was divided into serous and mucous types.The pH testing,Western Blotting(WB),and enzyme-linked immu-nosorbent assay(ELISA)were performed.Results ① There were 49.29％(35/71)of ASOM patients had a posi-tive RSI score(＞13).② The positive rate of pepsin in ASOM children was 49.29％(35/71),and the positive rate of trypsin was 42.25％(30/71).In addition,the positive rate of pepsin in RSI-positive children was 100％(35/35),and the positive rate of trypsin was 60％(21/35).There was no significant difference in the positive rate of pepsin and trypsin between serous and mucous middle ear effusion(P＞0.05).③ The pepsin concentration was 47.80(39.80,69.30)ng/ml and the trypsin concentration was 291.87±20.45 ng/ml in middle ear effusion of chil-dren with ASOM who had a positive WB test,and the trypsin concentration was significantly higher than pepsin(P＜0.05).There was no significant difference between the pepsin and the trypsin concentrations in serous and mu-cous middle ear effusion(P＞0.05).④ The pH value of mucous middle ear effusion was 7.39±0.28,and the pH value of serous middle ear effusion was 7.36±0.26.There was no significant difference between the pH value in se-rous and mucous middle ear effusion(P＞0.05).Conclusion The detection rates of pepsin and trypsin in middle ear effusion of children with ASOM were high which has important diagnostic value for children with ASOM combined with LPRD.

Objective To study the therapeutic effect of the type Ⅰ tympanoplasty by the continuous irriga-ting endoscopic ear surgery mode.Methods A total of 50 patients with chronic suppurative otitis media,who pre-pared for the type Ⅰ tympanoplasty in our department,were divided into the traditional operation mode group(20 cases)and the continuous irrigating mode group(30 cases).All patients underwent underlay myringoplasty with tragus cartilage and perichondria limplant.The operation time and postoperative outcome of the two groups were compared and analyzed.Results The mean operation time of the traditional group and the irrigating operation group was 66.10±2.43 minutes and 46.81±5.12 minutes respectively,and there was statistical difference between the two groups(P＜0.05).The tympanic membrane healing rate of the traditional group and the irrigating operation group was 100.00％and 96.67％respectively,and there was no statistical difference between the two groups(P＞0.05).The mean air conduction threshold and the value of air-bone gap were significantly reduced at 2 months after operation compared with that before operation(P＜0.05).There was no significant difference between the two groups in the average pre and post-operative air-bone gaps(P＞0.05).The incidence rates of postoperative compli-cations were 10.00％and 3.33％,respectively,with no statistical significance(P＞0.05).Conclusion The contin-uous irrigating endoscopic ear surgery mode is safe and effective.Under the premise of ensuring clinical efficacy,the operation time is shortened,and it is worth popularizing in middle ear surgery.

Objective To investigate the molecular genetic characteristics and clinical characteristics of severe combined immunodeficiency(SCID)in children caused by a novel mutation of interleukin 2 receptor gamma IL-2RG gene.Methods The clinical data,laboratory results and genetic testing data of a child with SCID admitted to the Department of Children's Hematology of Northwest Women and Children's Hospital were analyzed.Results A two-month-old male infant was admitted to the hospital for treatment due to recurrent infections after birth.The child's blood routine results showed that the total number of white blood cells was normal,but lymphocytes were decreased.The lymphocyte subpopulation results showed a significant decrease in the proportion of total T(CD3+),helper T(CD3+CD4+),killer T(CD3+CD8+),and NK(CD3-CD16+CD56+)lymphocytes,while the proportion of B(CD3-CD19+)lymphocytes were increased.The immunoglobulin levels showed a significant decrease in IgG,and IgM and IgA were below the lower detection limit.The patient's cytokine levels did not significantly increase during infection.In the last three generations of the mother's family,9 males died of infection within one year after birth.The whole exome sequencing results of the core family revealed a semi zygous new missense mutation[c.675 C＞A,p.S225R(p.Ser225Arg)]in the IL-2RG gene on the X chromosome(chrX:70329160)of the patient,and the mother was a carrier.Based on the above evidence,the child was diagnosed with X-SCID.Subsequently,intravenous immunoglobulin was injected monthly,and routine antibiotics and antiviral drugs were taken to prevent infection,preparing for hematopoietic stem cell transplantation.Because the child was vaccinated with BCG after birth,the child developed disseminated BCG disease at the age of 6 months.After treatment,hematopoietic stem cell transplantation was performed.Conclusion The immune function of the X-SCID patient was severely compromised,which endangered the patient's life,and vaccination with live vaccines may lead to severe infections.This study found that the c.675 C＞A mutation of the IL-2RG gene was a novel pathogenic variation of the genetic cause of X-SCID,expanding the mutation spectrum of the X-SCID pathogenic gene IL-2RG.