Objective To clarify the predominant symptoms of PH and their correlation with clinical indicators by collecting Chinese medicine clinical syndromic data of patients with pulmonary hypertension(PH).To provide a basis for the clinical diagnosis and treatment of Chinese medicine.Methods Adopting a cross-sectional study method,from January 2020 to July 2021,the cardiovascular ward of Guang'an men Hospital of the China Academy of Traditional Chinese Medicine was in line with the patients with the diagnosis of PH.A total of 298 patients'data were collected,and 236 patients were included in this study by excluding factors such as incomplete data and repeated hospitalization.The clinical data of the patients were organized,analyzed and counted.The distribution pattern of symptoms and syndrome types of PH was derived,and the correlation between syndrome elements and hemodynamics,cardiac function,and coagulation function was explored.Results The eight syndrome elements of PH in this study were,in descending order,blood stasis>Qi deficiency>water stagnation>phlegm turbidity>blood deficiency>yang deficiency>yin deficiency>qi stagnation;The eight syndrome types were in the order of high to low:Qi deficiency and blood stasis,spleen and lung deficiency,blood stasis and water stagnation,phlegm and water stagnation,phlegm and blood stasis stagnation,phlegm and water stagnation,yang deficiency and water stagnation,phlegm and turbid obstruction of lungs,and deficiency of both qi and yin;Qi deficiency was negatively correlated with Systolic pulmonary artery pressure(SPAP),and water stagnation was positively correlated with SPAP;Qi deficiency was negatively correlated with cardiac function grading,and water stagnation and phlegm turbidity evidence were positively correlated with cardiac function grading.Conclusion Blood stasis is the core pathogenesis of PH,and the clinical manifestations and symptoms of PH patients gradually transformed from qi deficiency through blood stasis to phlegm turbidity and water stagnation."Stasis"is present throughout the course of PH disease and has a significant impact on the progression of PH.

Objective To investigate the core drugs of traditional Chinese medicine(TCM)for the treatment of hypoxic pulmonary hypertension(HPH),and to verify the drug efficacy by hypoxia combined with Su5416(Hypoxia+Su5416,HySu)-induced PH mouse model.Methods Relevant literatures on TCM treatment of HPH in China Knowledge Network,Wanfang,Weipu were collected,screened and set up a database through the nerf criteria,and inputted into the software of traditional Chinese medicine inheritance assistance platform(V2.5)for the excavation of medication law.The HySu-PH mouse model was established,and the core drugs were evaluated for drug efficacy through force exhaustion exercise running table,blood oxygen saturation,right ventricular pressure,and right heart hypertrophy index test.Results The 102 relevant formulas for the treatment of HPH were screened,involving a total of 158 traditional Chinese medicines,and the top 5 drug frequencies were Salvia miltiorrhiza,Rhizoma Chuanxiong,Astragalus membranaceus,Draba hebecarpa,and Angelica sinensis,with the highest use of blood-activating and blood-stasis removing drugs,and deficiency-tonifying drugs in the categories of drugs used,and Salvia miltiorrhiza was the core drug used.HySu-PH mouse models were constructed and given 2 weeks of treatment with the danshen preparation Danshen injection.Danshen injection significantly elevated body weight(P<0.01),oxygen saturation(P<0.05),displacement of exhaustion(P<0.01),and duration of exhaustion(P<0.05),and lowered the right ventricular systolic blood pressure(P<0.01)and the right cardiac hypertrophy index(P<0.01).Conclusion Salvia miltiorrhiza is a core drug for the treatment of HPH,and the danshen preparation Danshen injection can effectively treat HySu-PH.

Objective Based on the pre-existing basis of effective treatment of hypoxia combined with Su5416-induced hypoxic pulmonary hypertension(HPH)by Salvia miltiorrhiza,to investigate the mechanism of Salvia miltiorrhiza in the treatment of HPH.Methods Using a network pharmacology approach to obtain the key pathways of Salvia miltiorrhiza for the treatment of HPH.The active ingredients of Salvia miltiorrhiza were collected to obtain the targets of the active ingredients.HPH disease targets were collected to obtain the intersection of Salvia miltiorrhiza component targets and HPH disease targets.Protein-Protein Interaction Networks(PPIs)were constructed and KEGG analysis was performed to obtain the key pathways of Salvia miltiorrhiza for HPH.Then used molecular biology to validate the key pathways.Results The 81 targets of Salvia miltiorrhiza for the treatment of HPH were obtained by network pharmacology,and PPI showed that drug component-disease common core targets included ATK1,TNF,EGFR,IL6,ESR1,and KEGG-enriched Pathway mainly included PI3K-AKT signaling pathway,HIF-1 signaling pathway,MAKP signaling pathway,TNF signaling pathway,JAK-STAT signaling pathway and so on.Molecular biological assays showed that Salvia miltiorrhiza had the effect of reducing lung tissue fibrosis and inhibiting the PI3K/AKT signalling pathway in HySu-PH mice.Conclusion Salvia miltiorrhiza has the effect of attenuating pulmonary fibrosis,and its mechanism of action is related to the inhibition of the PI3K/Akt signalling pathway.

Objective:To investigate the clinicopathological features and genetic characteristics of congenital cystic adenomatoid malformation (CCAM) of lung and CCAM associated lung cancer in adults.Methods:A total of 13 cases of CCAM of lung in adults, diagnosed from June 2015 to May 2023, were collected from the Department of Pathology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, China. Their histopathological features were correlated with probable development into lung cancer. Next-generation sequencing was performed on the benign and malignant areas of all cases.Results:The pathological classification of all cases were of CCAM of lung type 1. There were 4 male and 9 female cases, age ranged from 18 to 65 years, with a mean age of 41 years. Six cases were accompanied by lung cancer, all of them were mucinous adenocarcinoma. Next-generation sequencing showed no gene mutation in 2 of the 13 cases; KRAS mutations in exon 2 were detected in 7 cases, in which there were 6 cases complicated with lung mucinous adenocarcinoma and no matter in the malignant or benign regions, the same case exhibited the same mutation sites in KRAS gene.Conclusions:CCAM of the lung is a congenital disease, and in adults, type 1 is most commonly found in the pathological classification, and it is often accompanied by cancer. Gene mutations are frequently detected in CCAM of the lung, KRAS being the most recurrent mutation which may play an important role in the carcinogenesis.

Objective To establish a rapid detection and identification method for the chemical components of Longshengzhi capsules based on UPLC-Q-TOF/MS.Method UPLC-Q/TOF-MS technology was used to analyze and identify the chemical components of Longshengzhi capsules.The chromatographic column was a Waters Acquity UPLC BEH C18 column(100mm×2.1mm,1.7 μm),and the mobile phase A was 0.1%formic acid water.The mobile phase B was a methanol acetonitrile(1∶1)solution containing 0.1%formic acid(B).The flow rate is 0.3mL/min,the column temperature is 40℃,and the injection volume is 2 μL.The ion source adopts the electric spray ion source.The data is collected in the positive and negative ion modes,and the collection range is m/z 50～1200.The identification and matching are carried out through UNIFI software combined with manual verification of chemical components.Result 87 chemical components were preliminarily and rapidly identified.Conclusion The established method can systematically and rapidly analyze the chemical components in Longsheng leeches,providing a basis for the study of medicinal substances and having important significance for the quality control of Longsheng leeches.

Autoimmune diseases（ADs） are diseases in which the body’s immune tolerance is impaired， causing damage to its tissues. The pro-inflammatory helper T cell 17 （Th17） and anti-inflammatory regulatory T cell （Treg） are functionally antagonistic to each other， and the immune imbalance between them and the imbalance of related inflammatory factors are closely related to the occurrence of a variety of ADs. Plenty of evidence has shown that gut microbiota can regulate Th17/Treg differentiation， rebuild immune tolerance and delay the ADs process through regulating cytokine production， transcription factor expression and energy metabolism. This paper reviews the intervention effects of traditional Chinese medicine（TCM） monomers on the common ADs by regulating Th17/Treg differentiation balance based on intestinal flora： ulcerative colitis，rheumatoid arthritis and diabetes mellitus type 1. It is found that its mechanism of action may be to restore the balance of pro-inflammatory factors and anti-inflammatory factors to alleviate intestinal mucosal barrier damage， reduce synovial angiogenesis and improve pancreatic β cell destruction， which provides some ideas for the prevention and treatment of ADs with integrated traditional Chinese and western medicine.

Objective:To investigate the effect and feasibility of an in vitro three-dimensional model for angiogenesis of Kaposiform hemangioendothelioma (KHE). Methods:In April 2019, a 4-month-old boy with KHE received surgery in the department of hemangioma of Henan Provincial People’s Hospital. The tumor tissue was used for the angiogenesis model. Treated tissue was planted in a fibrin gel culture system constructed by a double-layer sandwich method to establish a three-dimensional angiogenesis model. Optimum humidity and constant temperature was provided for the culture system, and the medium was changed every other day. The growth of model was observed every day. When the model became stable, well-grown models were made into frozen sections for HE and immunohistochemistry staining.Results:The model formed newborn vascular buds within 2-4 days and became stable in 12-16 days. The newborn vessels staggered into networks and showed obvious lumen-like structure. Apoptosis started after 26-30 days in most models, while no apoptosis appeared until 54 days in some ones. Morphological observation, HE staining, and immunohistochemistry examination confirmed that KHE endothelia have formed the new vessels.Conclusions:The culture system of fibrin gel is applicable for three-dimensional angiogenesis model of Kaposiform hemangioendothelioma. It is characterized with short culture time, long survival time, simple operation, low cost, and easy intervention.

Objective:To investigate the effect and feasibility of an in vitro three-dimensional model for angiogenesis of Kaposiform hemangioendothelioma (KHE). Methods:In April 2019, a 4-month-old boy with KHE received surgery in the department of hemangioma of Henan Provincial People’s Hospital. The tumor tissue was used for the angiogenesis model. Treated tissue was planted in a fibrin gel culture system constructed by a double-layer sandwich method to establish a three-dimensional angiogenesis model. Optimum humidity and constant temperature was provided for the culture system, and the medium was changed every other day. The growth of model was observed every day. When the model became stable, well-grown models were made into frozen sections for HE and immunohistochemistry staining.Results:The model formed newborn vascular buds within 2-4 days and became stable in 12-16 days. The newborn vessels staggered into networks and showed obvious lumen-like structure. Apoptosis started after 26-30 days in most models, while no apoptosis appeared until 54 days in some ones. Morphological observation, HE staining, and immunohistochemistry examination confirmed that KHE endothelia have formed the new vessels.Conclusions:The culture system of fibrin gel is applicable for three-dimensional angiogenesis model of Kaposiform hemangioendothelioma. It is characterized with short culture time, long survival time, simple operation, low cost, and easy intervention.

Objective:To pathologically evaluate the surgically resected specimens of three different therapies (neoadjuvant chemotherapy, neoadjuvant targeted therapy and neoadjuvant immunotherapy combined with chemotherapy) for non-small cell lung cancer.Methods:One-hundred and thirteen cases of post neoadjuvant therapy non-small cell lung cancer specimens were collected at Tongji University Affiliated Shanghai Pulmonary Hospital from January 2000 to March 2020. There were ninty patients receiving neoadjuvant chemotherapy (chemotherapy group;26 cases of adenocarcinoma and 64 cases of squamous cell carcinoma), 13 patients receiving neoadjuvant targeted therapy (targeted group;13 cases of adenocarcinoma) and 10 patients receiving neoadjuvant immunotherapy combined with chemotherapy (immune combined chemotherapy group;4 cases of adenocarcinoma and 6 cases of squamous cell carcinoma). They were evaluated for histologic tumor regression responses (necrosis, inflammatory cell infiltration, cholesterol crystal deposition, foam cell infiltration, reactive granuloma and interstitial collagenous formation) and pathological responses [main pathological response (MPR) and complete pathological response (PCR)].Results:Chemotherapy group, targeted group and immune combined chemotherapy group all showed degenerative changes in residual tumor cells, increased atypia, various degrees of necrosis, foam cell aggregation, cholesterol cleft, inflammatory cell infiltration, and reactive granuloma in the tumor bed. Histologic characteristics of tumor regression reaction were not different between these three groups ( P>0.05); the highest percentage of necrosis in the targeted group and immune combined chemotherapy group was only 10% and 20%, respectively, while that in the chemotherapy group was as high as 80%. One case of adenocarcinoma in immune combined chemotherapy group had tumor regression bed. The MPR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 35% (9/26) and 64% (41/64), respectively; the MPR ratio of targeted group was 2/13; the MPR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinoma in immune combined chemotherapy group were 2/4 and 2/6, respectively. The PCR rates of adenocarcinoma in chemotherapy group and squamous cell carcinoma in chemotherapy group were 11% (3/26) and 3% (2/64), respectively; the PCR ratio of targeted group was 0/13; the PCR ratio of adenocarcinomain immune combined chemotherapy group and squamous cell carcinomain immune combined chemotherapy group were 0/4 and 1/6, respectively. Conclusions:Different neoadjuvant therapy may cause various histopathological changes in non-small cell lung cancer: more necrosis is noted in the chemotherapy group and regression bed frequently appears in the immune combined chemotherapy group. In the immune combined chemotherapy group, there are significant lymphoplasmacytic infiltration and lymphoid follicle formation in the lung parenchyma beside the tumor bed.

Objective:To analyze efficacy of comprehensive surgical treatment for Kasabach-Merritt phenomenon (KMP) .Methods:Clinical data were collected from 18 patients with KMP who underwent surgical treatment in Department of Hemangioma, Henan Provincial People′s Hospital from November 2017 to March 2019, and analyzed retrospectively. Preoperative treatment included preoperative use of glucocorticoids and immunoglobulins to increase platelet counts in patients. For patients irresponsive to glucocorticoids, a single large-dose of platelets was infused 12-24 hours before surgery. The platelet dose for infusion should be 0.3 and 0.2 therapeutic dose (TD) /kg respectively for patients with platelet counts lower than 30 × 10 9/L and those with platelet counts higher than 30 × 10 9/L, and the total infusion dose should be no more than 1 TD (containing about 2.5 × 10 11 platelets in 200-250 ml of infusion solution) . During the operation, tumor tissues were removed as much as possible; if there were difficulties in suturing in patients with large tumors, in situ autologous skin grafting would be performed; for children with potential postoperative functional dysfunction, a clinical consultation with rehabilitation specialists was given, and individualized functional exercises were prescribed to promote functional restoration. Results:Eighteen patients were enrolled, including 9 males and 9 females, with an average age of 73 days (range, 7-354 days) . Skin lesions were located on the extremities in 3 cases, on the trunk in 11, and on the head, face and neck in 4. Surgeries were successful in 17 patients, but 1 died. Among the 17 patients with successful operation, platelet counts and coagulation function returned to normal within 1 week after the surgery in 16, and did not returned to normal until after regular oral administration of sirolimus in 1. Favorable movement ability was maintained in all the children.Conclusion:Comprehensive surgical treatment shows rapid efficacy with less adverse reactions in the therapy of KMP.