Evaluación de la expresión de PD-L1 e infiltración linfocitaria intratumoral en carcinoma de mama invasivo triple negativo / Evaluation of PD-L1 expression and intratumoral lym phocytic infiltration in triple-negative invasive breast car cinoma

Resumen Introducción : El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos : Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado his tológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados : Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumo ral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos res pectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión : Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instau ración de terapias diana y el desarrollo de la medicina de precisión.

Abstract Introduction : Triple negative breast cancer endophe notype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the es tablishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. Methods : A retrospective case-control study was performed, with 31 cases of triple-negative infiltrat ing breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. Results : a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). Discussion : The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the develop ment of precision medicine.

PKMYT1 Promotes Epithelial-Mesenchymal Transition Process in Triple-Negative Breast Cancer by Activating Notch Signaling

ABSTRACT Background: Triple-negative breast cancer (TNBC) is a subtype of breast cancer (BC) that lacks receptors for targeted therapy. Deeper insight into the molecular mechanisms regulating TNBC metastasis is urgently needed. The epithelial-mesenchymal transition process facilitates the metastasis of neighboring epithelial tumor cells. Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1), a member of the Wee family of protein kinases, is upregulated in BC, and its high expression predicts poor prognosis in BC patients. Notch signaling activation is a pathognomonic feature of TNBC. PKMYT1 has been found to induce EMT in non-small cell lung cancer by activating Notch signaling. However, whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling remains unknown. Objectives: The objective of this study was to investigate whether PKMYT1 exerts effects on TNBC progression by regulating Notch signaling. Methods: Fifty cases of surgically resected BC samples (tumor and adjacent non-tumor tissue samples) were collected from patients diagnosed with BC. We measured the expression of PKMYT1 in clinical samples with real-time quantitative polymerase chain reaction (RT-qPCR). For in vitro analysis, RT-qPCR and Western blotting were conducted to evaluate PKMYT1 expression in TNBC cells. Then, the viability, migration, and invasion of TNBC cells were detected by cell counting kit-8 assays, wound healing assays, and Transwell assays. The EMT event was examined by evaluating the levels of EMT-associated proteins. For in vivo analysis, xenograft models in nude mice were established to explore PKMYT1 roles. E-cadherin and Ki67 expression in xenograft models were estimated by immunohistochemistry staining. Hematoxylin and eosin staining was performed to assess tumor metastasis. The underlying mechanisms by which PKMYT1 affected the malignant phenotypes of TNBC cells were explored by Western blotting measuring the pathway-associated proteins. Results: PKMYT1 was upregulated in BC tissues and cells, and its knockdown prevented cell proliferation, migration, invasion, and EMT event in TNBC. Mechanistically, Notch signaling was inactivated by PKMYT1 depletion, and Notch activation abolished the PKMYT1 silencing-induced inhibition in the malignant phenotypes of TNBC cells. For in vivo analysis, PKMYT1 knockdown inhibited tumorigenesis and metastasis of TNBC. Conclusion: PKMYT1 promotes EMT, proliferation, migration, and invasion of TNBC cells and facilitates tumor growth and metastasis by activating Notch signaling.

Clinical Efficacy of Modified Yigongsan Combined with Multi-enzyme Tablets and Bifidobacterium Triple Live Powder in Treatment of Infantile Anorexia with Spleen-Stomach Qi Deficiency Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of modified Yigongsan combined with multi-enzyme tablets and bifidobacterium triple live powder on infantile anorexia with spleen-stomach Qi deficiency syndrome. MethodA total of 112 infantile patients anorexia with spleen-stomach Qi deficiency syndrome treated at Hebei Provincial Hospital of Traditional Chinese Medicine from January 2022 to June 2023 were enrolled and divided into a control group and an observation group， with 56 cases in each group， according to a random number table. Children in the control group were treated with multi-enzyme tablets and Bifidobacterium triple live powder， while those in the observation group were treated with modified Yigongsan in addition to the treatment in the control group. During the study， one case dropped out in the control group and two cases dropped out in the observation group. The clinical efficacy of the two groups of children was compared， including changes in traditional Chinese medicine （TCM） syndrome scores （main symptoms， secondary symptoms， tongue， and pulse）， time to restore normal food intake， and increase in body weight. Changes in calcium， iron， zinc levels， hemoglobin， and albumin levels before and after treatment， as well as changes in gastrointestinal hormones such as gastrin and motilin， vasoactive intestinal peptide， somatostatin， neuropeptide Y， orexin， and leptin， were observed. The occurrence of adverse reactions in the two groups of children during the study was also recorded. ResultThe total effective rate of children in the control group after treatment was 85.19% （46/54）， while that in the observation group was 98.15% （53/54） （χ2 =5.939， P<0.05）. Compared with the control group， the time for food intake to return to normal in the observation group was shorter， and the increase in body weight was greater （P<0.05）. Compared with the results before treatment， the TCM syndrome scores （main symptoms， secondary symptoms， tongue， and pulse） in both groups of children significantly decreased， while the levels of calcium， iron， zinc， hemoglobin， albumin， gastrin， motilin， neuropeptide Y， and orexin increased， and the levels of vasoactive intestinal peptide， somatostatin， and leptin decreased （P< 0.01）. Compared with the control group after treatment， the improvement in the above indicators in the observation group was more significant （P<0.01）. The incidence of adverse reactions in the two groups of children during the treatment period was similar， and the difference was not statistically significant. ConclusionModified Yigongsan combined with multi-enzyme tablets and Bifidobacterium triple live powder is highly effective in treating infantile anorexia （spleen-stomach Qi deficiency syndrome）. After treatment， symptoms of the children were improved，appetite and food intake increased， gastrointestinal function was improved， body weight increased， and adverse reactions were few， indicating that the treatment was safe and reliable.

Mechanism of Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) against chronic heart failure based on the thought of "Four in One" with the theory of "Qi transformation in triple energizer" / 国际中医中药杂志

The "four-in-one" approach is based on the four-dimensional perspective of "property, position, tendency and syndrome", which helps to identify and analyze classical prescriptions in a multi-dimensional and three-dimensional way. The early pathogenesis of chronic heart failure (CHF) is deficiency of heart Qi and heart Yang and disorder in Qi transformation in triple energizer, while in the later stage of the disease, it progresses from deficiency to excess, with simultaneous occurrence of deficiency and excess syndromes. Fuling Guizhi Baizhu Gancao Decoction (Linggui Zhugan Decoction) plays its role in treating chronic heart failure by the four elements of "property, position, tendency and syndrome". Property—Linggui Zhugan Decoction is pungent, sweet, slight sweet and bitter in flavor, but warm in property. The sweet is able to tonify deficiency; the pungent is responsible for dispersing Yang, promoting Qi and draining water retention; the warm nourishes the spleen, raises Yang Qi and resolves phlegm; the bitter could excrete diuresis and dry dampness to guarantee the smooth operation of three energizer. Position-Linggui Zhugan Decoction acts on the heart, spleen and triple energizer. It can stimulate heart Yang, strengthen the spleen, resolve phlegm, and regulate the waterways to promote the Qi transformation in triple energizer. Tendency-The tendency of Linggui Zhugan Decoction is upward and downward in parallel, both internal and external. Warming up and promoting diuresis, raising Yang up and tonifying deficiency, it is conducive to the Yang Qi transformation in triple energizer. Syndrome-Linggui Zhugan Decoction is indicated for the syndrome of heart Yang deficiency and water-fluid retention, which begins with the upper abdomen swelling, Qi rushes against the chest. It is widely used in the treatment of water-vapor impulse heart disease. The disorder of Qi transformation in triple energizer is the main mechanism of recurrent CHF. Linggui Zhugan Decoction can not only warm the fire of Qi transformation in triple energizer, but also smooth the pathway of Qi transformation in triple energizer, which is compatible with the treatment of systemic fluid retention in chronic heart failure. Its pharmacological mechanisms include anti-inflammation, anti-platelet aggregation, regulation of cardiomyocyte cell membrane ion channels, protection against ischemia-reperfusion injury and modulation of vasodilation, etc. Deconstructing Linggui Zhugan Decoction with "four-in-one" approach and discussing its mechanism for treating CHF in combination with the theory of "Qi transformation in triple energizer", have great significance to rejuvenate the vitality of classical prescriptions and to apply them accurately and effectively.

Exploring mechanism of Huayu Pills combined with immunocheckpoint inhibitors in treating triple-negative breast cancer based on network pharmacology / 国际中医中药杂志

Objective:To explore the potential mechanism of Huayu Pills in the treatment of TNBC (triple-negative breast cancer) using network pharmacology.Methods:TCMSP (Traditional Chinese Medicine Systems Pharmacology), PubChem, STITCH and SwissTargetPrediction databases were used to analyze the potential targets of Huayu Pills. TNBC disease targets were screened based on the TCGA (The Cancer Genome Atlas) database. The drug-disease mapping target was constructed by PPI network, key target screening and module analysis, and the DAVID database was used for GO function annotation and KEGG signal pathway enrichment analysis. SD rats were orally administered 3.94 g/kg of Huayu Pills decoction for 4 days to prepare medicated serum. HUVEC cells were randomly divided into a control group and an experimental group using a random number table method. The experimental group received intervention with Huayu Pills containing serum for 24 hours, inoculated in matrigel's solidified 48 well plate and HUVEC angiogenesis was observed 3 hours later.Results:130 possible targets of Huayu Pills in the treatment of TNBC were obtained. VEGFA is the core target. The cascade of angiogenesis, hypoxia, and blood coagulation may be the main functions and key signals of Huayu Pills in the treatment of TNBC. In vitro studies have shown that serum containing Huayu Pills can promote the normalization of tumor blood vessels in HUVEC cells.Conclusion:Huayu Pills may promote tumor vascular normalization (angiogenesis, hypoxia, coagulation cascade reactions) through VEGF targets, and can assist immune checkpoint inhibitors in the treatment of TNBC.

An Analysis of YU Hai-Bo's Experience in Treating Paediatric Cerebral Palsy by Using"Jianpi Yishen Triple-Needle Grouping Acupoints" / 广州中医药大学学报

This article introduces the clinical approach and acupuncture characteristics of the traditional Chinese medicine practitioner Professor YU Hai-Bo in treating paediatric cerebral palsy using the"Jianpi Yishen Triple-Needle Grouping Acupoints".Guided by the theory of growth and development of"viscera-meridian-brain"growth and development,Professor YU believed that"insufficiency of spleen and kidney"is the core pathogenesis of paediatric cerebral palsy,and the treatment concept of"treating from the spleen and kidney"was proposed.He inherited and innovated the triple-needle grouping acupoints therapy and establishing the system of"Jianpi Yishen Triple-Needle Grouping Acupoints".Before regular acupuncture,the abdomen and dorsum are pricked to freely regulate the middle energizer,and the upper limbs are selected as"Hegu(LI4),Waiguan(SJ5),Quchi[(LI11),three acupoints on the hand]+ Neiguan(PC6)";the lower limbs are selected as"Zusanli(ST36),Sanyinjiao(SP6),Taichong[(LR3),three acupoints on the foot];"Shenmai(BL62),Zhaohai(KI6),Yongquan(KI1)",spleen and kidney are regulated simultaneously,and the head acupoints include Sishencong(EX-HN1),intelligence tri-needling,cerebral tri-needling,temporal tri-needling,mind-calming needling and bilateral Fengchi(GB20).In order to regulate the spirit and benefit the intellect,the matching acupoints are modified according to the disease and the syndromes.At the same time,it is supplemented with music therapy and auricular point seed-pressing.Emphasis is placed on the simultaneous regulation of"child-parent-doctor"and"treating the person"rather than the"treating the disease".

Effects of Fuzheng Quxie Prescription Combined with Neoadjuvant Chemotherapy on Tumor Recurrence,Serum Thymidine Kinase 1 Level and Immune Function in Patients with Triple-Negative Breast Cancer / 广州中医药大学学报

Objective To investigate the effects of Fuzheng Quxie Prescription(mainly with the actions of supporting healthy qi and dispelling pathogens)combined with neoadjuvant chemotherapy on tumor recurrence,serum thymidine kinase 1(TK1)level and immune function in patients with triple-negative breast cancer(TNBC).Methods Eighty patients with TNBC of qi and yin deficiency type were randomly divided into a combination group and a control group,with 40 patients in each group.The control group was treated with AC-T sequential chemotherapy(Doxorubicin combined with Cyclophosphamide plus sequential Docetaxel),and the combination group was treated with Fuzheng Quxie Prescription on the basis of treatment for the control group.One course of treatment covered 21 days,and the two groups were treated for 4 consecutive courses.The changes of traditional Chinese medicine(TCM)syndrome scores,Karnofsky Performance Status(KPS)score,levels of tumor markers of carbohydrate antigen 125(CA125),carbohydrate antigen 153(CA153)and TK1,and T lymphocyte subset levels in the two groups were observed before and after the treatment.Moreover,the clinical efficacy and tumor metastasis and recurrence in the two groups were compared.Results(1)After 4 courses of treatment,the total effective rate of the combination group was 87.50%(35/40),and that of the control group was 67.50%(27/40),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the combination group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the TCM syndrome scores in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the KPS scores were significantly increased compared with those before treatment(P＜0.05),and the decrease of TCM syndrome scores and the increase of KPS scores in the combination group were significantly superior to that in the control group(P＜0.05 or P＜0.01).(3)After treatment,the serum CA125,CA153 and TK1 levels of patients in the two groups were significantly decreased compared with those before treatment(P＜0.05),and the decrease of serum CA125,CA153 and TK1 levels in the combination group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio in the two groups were significantly increased compared with those before treatment(P＜0.05),and the CD8+ level was significantly decreased compared with that before treatment(P＜0.05).The post-treatment intergroup comparison showed that the increase of the T lymphocyte subset CD3+,CD4+ levels and CD4+/CD8+ ratio as well as the decrease of the CD8+ level in the combination group was all significantly superior to that in the control group(P＜0.05 or P＜0.01).(5)The one-year follow-up showed that the tumor recurrence rate and tumor metastasis rate in the combination group were 7.50%(3/40)and 12.50%(5/40)respectively,significantly lower than 25.00%(10/40)and 35.00%(14/40)in the control group,and the differences were statistically significant when comparing between the two groups(P＜0.05).Conclusion The combination of neoadjuvant chemotherapy with Fuzheng Quxie Prescription has a better therapeutic effect on TNBC patients with qi and yin deficiency syndrome,which can effectively improve the immune function of the patients,decrease the level of serum tumor markers,improve the quality of life of the patients,and reduce the incidence of tumor recurrence and metastasis.

LI Fei's Experience in Treating Facial Paralysis with Acupuncture and Moxibustion / 广州中医药大学学报

This article aims to analyze LI Fei's academic thinking and experience in treating facial paralysis.LI Fei proposes that the diagnosis and treatment of facial paralysis should follow the principle of"identify the cause of the disease when it is occured at first time,followed by exploring the pathogenesis of the disease,then differentiating the syndrome and treating the disease,and recognizing the syndrome and treating the disease",and that the basic treatment principle should be"dispelling wind and unblocking the collaterals,regulating the tendons and meridians".In clinical treatment,"put emphasis on anatomy,treat the disease according to symptoms"is the basic policy;meanwhile,integrating Chinese and western theories,combining the anatomical structure of the expression muscle,dynamically judging the recovery of nerves and muscles,and selecting the corresponding empirical acupoints according to the symptoms.LI Fei emphasizes the integration of theories and summarizes the"triple"methods of differentiation by reasoning,staging and symptoms,and the"triple"theory of treatment by regulating menstruation,tendon and spirit,which is worthy of reference in the clinic.

Study on the Treatment of Dampness Stagnated in the Triple Energizer Based on the Theory of"Qi Transformation Leading to the Removal of Pathogenic Dampness" / 广州中医药大学学报

The statement of"qi transformation leading to the removal of pathogenic dampness"was recorded in Wen Bing Tiao Bian(Analysis on Epidemic Febrile Diseases)written by the Qing Dynasty physician WU Ju-Tong.Dampness in the triple energizer is caused by the dysfunction of qi transformation,and the treatment of dampness must be based on the activation of qi movement and focused on the promotion of qi movement and the restoration of the qi transformation in the triple energizer.For the treatment of dampness attack in the upper energizer,therapies of dispersing lung to smooth qi and resolving dampness to relieve the obstruction are recommended.For the treatment of dampness obstruction in the middle energizer,therapy of activating spleen qi by strengthening spleen and moving qi is stressed for helping the removal of dampness and for the eradication of the source of dampness.For the treatment of dampness stagnation in the lower energizer,therapy of draining dampness with sweet-light medicines and activating yang can be used according to the illness status.The three methods of treating dampness,namely dispersing the upper energizer,activating the middle energizer and draining the lower energizer,all embody the mechanism of"qi transformation leading to the removal of pathogenic dampness",and the therapies of dispersing lung with light medicines,inducing perspiration by opening striated layer,eliminating dampness with aromatics and draining dampness with sweet-light medicines should be used in accordance with the syndromes.The elucidation of the academic thoughts of"qi transformation leading to the removal of pathogenic dampness"can provide theoretical reference for the fundamental research of dampness syndrome and clinical application of therapies for resolving dampness in Chinese medicine.

Diagnostic value of serum ficolin-3 and collagen triple helix repeat containing-1 for non-small cell lung cancer and their relationship with clinicopathological characteristics / 临床外科杂志

Objective To explore the diagnostic value of serum ficolin-3(FCN3)and collagen triple helix repeat containing-1(CTHRC1)in non-small cell lung cancer(NSCLC)and their relationship with clinicopathological characteristics.Methods From July 2021 to August 2022,73 patients with NSCLC who were admitted to the our Hospital were selected as the study group,and 55 healthy people who came to our hospital for physical examination were regarded as the control group.the serum levels of FCN3 and CTHRC1 were measured by enzyme-linked immunosorbent assay(ELISA);Pearson method was applied to analyze the correlation of serum FCN3 and CTHRC1 levels in NSCLC patients;Logistic regression analysis was applied to analyze the influencing factors of NSCLC;the diagnostic value of serum FCN3 and CTHRC1 levels on the occurrence of NSCLC was analyzed by the ROC curve.Results The levels of serum FCN3 and CTHRC1 in the study group were obviously higher than those in the control group(P＜0.05);the levels of serum FCN3 and CTHRC1 were correlated with the degree of cancer cell differentiation,TNM stage and lymph node metastasis in NSCLC patients(P＜0.05);Pearson method analysis showed that there was a positive correlation between serum FCN3 and CTHRC1 levels in NSCLC patients(r=0.258,P=0.028);Logistic regression analysis showed that serum FCN3 and CTHRC1 were the influencing factors of NSCLC(P＜0.05);the area under the ROC curve of serum FCN3 and CTHRC1 levels in diagnosis of NSCLC was 0.869 and 0.810,respectively,the area under the ROC curve of NSCLC was 0.881,which were better than those of serum FCN3 and CTHRC1.Conclusion The levels of serum FCN3 and CTHRC1 in patients with NSCLC increase,which are related to the degree of cancer cell differentiation,TNM stage and lymph node metastasis,they are risk factor for NSCLC,and the combination of the two is more valuable in diagnosis of NSCLC.

Triple negative breast cancer:a study based on histological and immunohistochemical classification / 临床与实验病理学杂志

Purpose To evaluate the classification criteria of triple negative breast cancer(TNBC)based on histomorphol-ogy and immunohistochemistry(IHC),and to provide theoreti-cal basis for the classification and treatment of TNBCs.Methods TNBC subtyping was performed according to the histomorphologi-cal characteristics and the expression of immune markers AR,CD8 and FOXC1,and the clinicopathological features and prog-nostic differences were compared.Results Among 93 cases of TNBC,there were 23 cases(24.7％)of luminal androgen re-ceptor subtypes,24 cases(25.8％)of immunomodulatory type,39 cases(42.0％)of basal immunosuppressive type,and 7 ca-ses(7.5％)of mesenchymal type.There were significant differ-ences in the clinicopathological features of subtypes,including pT stage(P=0.030),histological grade(P＜0.001),intersti-tial lymphocyte infiltration pattern(P＜0.001),expression of PD-L1(P＜0.001),and HER2-low(P=0.024).There was no significant difference in disease-free survival among the sub-types(P＞0.05).Univariate survival analysis showed there was significant difference in disease-free survival among the subtypes at pT1 stage(P=0.011),and other clinicopathological features were not independent prognostic factors.Conclusion The clini-copathological characteristics of TNBC subtypes are different,which are expected to be an alternative choice for complex gene expression profile analysis and to provide theoretical basis for subtypic therapy and targeted therapy.

The clinical study of combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus assisted triple therapy in chronic gastritis children with Helicobacter pylori positive / 中国医师进修杂志

Objective:To study the clinical effect of combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus assisted triple therapy in chronic gastritis children with Helicobacter pylori ( Hp) positive. Methods:The clinical data of 80 chronic gastritis children with Hp positive from January 2019 to March 2022 in Wuxi Children′s Hospital were retrospectively analyzed. Among them, 40 children (combination group) were treated with combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus combined with triple therapy (omeprazole, amoxicillin and clarithromycin), 40 children (control group) were treated with triple therapy, and all children were treated for 4 weeks. The efficacy, Hp clearance rate (performed 13C breath test after 4 weeks of discontinuation) and symptom improvement (the scores of upper abdomen pain, anorexia and sour regurgitation) were compared between two groups. The feces before treatment and after treatment were collected, and the intestinal flora was detected, including Bifidobacterium, Lactobacillus, Bifidobacterium/ Enterobacteria; the levels of C-reactive protein (CRP), tumor necrosis factor α (TNF-α), interleukin 10 (IL-10) and nuclear transcription factor κB (NF-κB) before treatment and 14 d after treatment were detected; the adverse reactions (vomiting, diarrhea, dizziness and erythra) were detected. Results:The total effective rate and Hp clearance rate in combination group were significantly higher than those in control group: 95.00% (38/40) vs. 80.00% (32/40) and 92.50% (37/40) vs. 75.00% (30/40), and there were statistical differences ( P<0.05). The scores of upper abdomen pain, anorexia and sour regurgitation after treatment in combination group were significantly lower than those in control group: (0.56 ± 0.14) scores vs. (1.12 ± 0.35) scores, (1.20 ± 0.37) scores vs. (1.50 ± 0.42) scores and (1.02 ± 0.28) scores vs. (1.39 ± 0.43) scores, and there were statistical differences ( P<0.01). The Bifidobacterium, Lactobacillus, Bifidobacterium/ Enterobacteria after treatment in combination group were significantly higher than those in control group: (8.56 ± 1.35) lgcfu/g vs. (7.94 ± 1.32) lgcfu/g, (9.27 ± 1.63) lgcfu/g vs. (8.35 ± 1.58) lgcfu/g and 1.85 ± 0.40 vs. 1.25 ± 0.34, and there were statistical differences ( P<0.01). The CRP, TNF-α and NF-κB after treatment in combination group were significantly lower than those in control group: (12.06 ± 3.14) ng/L vs. (17.36 ± 3.08) ng/L, (10.74 ± 3.25) μg/L vs. (15.30 ± 4.18) μg/L and (1.17 ± 0.34) μg/L vs. (2.21 ± 0.82) μg/L, the IL-10 after treatment was significantly higher than that in control group: (43.14 ± 6.38) μg/L vs. (35.29 ± 5.03) μg/L, and there were statistical differences ( P<0.01). There was no statistical difference in the incidence of adverse reactions between two group ( P>0.05). Conclusions:The combined capsules of live Bifidobacterium, Lactobacillus and Enterococcus assisted triple therapy has clear efficacy in chronic gastritis children with Hp positive, with few adverse reactions. It can significantly improve clinical symptoms, and its mechanism may be related to the regulation of intestinal microbiota and serum inflammation.

PDHA1 promotes proliferation,invasion and metastasis of triple-nega-tive breast cancer cells / 中国病理生理杂志

AIM:One of the important characteristics of the occurrence and development of triple-negative breast cancer(TNBC)is dysregulated cell metabolism.The aim of this study is to investigate the mechanism of pyruvate dehydrogenase E1 subunit alpha 1(PDHA1),a key enzyme component in aerobic glycolysis,affecting the proliferation,metastasis and invasion of TNBC.METHODS:(1)The expression levels of PDHA1 in breast cancer tissues and adja-cent tissues were analyzed by UALCAN database,KM-plotter database,Gene MANIA database and TCGA database.The expression of PDHA1 was compared according to tumor pathological stage,subtype classification and breast cancer bio-markers.The function of PDHA1 in TNBC was explored by gene enrichment analysis.(2)Immunohistochemistry assays were used to detect the expression of PDHA1 in human TNBC tissue and adjacent tissue samples.(3)Stable PDHA1 knockout and PDHA1 rescue TNBC MDA-MB-231 cells were constructed.The proliferation of MDA-MB-231 cells was de-tected by colony formation assay and cell counting assay.The regulatory effect of PDHA1 on the invasion and migration of MDA-MB-231 cells was detected by in vitro scratch assay and Transwell migration assay.RESULTS:Database analysis showed that the group with high PDHA1 expression in breast cancer had shorter survival and worse prognosis.In clinical specimens,the expression of PDHA1 in cancer tissues was higher than that in adjacent normal tissues.Knockout of PDHA1 inhibited the proliferation,metastasis,invasion and epithelial-mesenchymal transition of MDA-MB-231 cells.CONCLUSION:PDHA1 is overexpressed in TNBC,and it promotes cell proliferation and facilitates TNBC metastasis through the epithelial-mesenchymal transition pathway.

Effect of circDNMT1 regulating miR-377-3p/PUM1 axis on proliferation,apoptosis and epithelial-mesenchymal transition of triple-negative breast cancer cells / 局解手术学杂志

Objective To investigate the effects of circDNMT1 on the proliferation,apoptosis and epithelial-mesenchymal transition(EMT)of triple-negative breast cancer(TNBC)cells by regulating miR-377-3p/PUM1 axis.Methods The TNBC tissues and adjacent normal tissues of 24 patients with TNBC treated in Danzhou People's Hospital from 2018 to 2021 were collected.qRT-PCR and Western blot were used to detect the expression of circDNMT1,miR-377-3p,and PUM1 protein in tissue and mouse normal breast epithelial cell line HC11 and TNBC cell lines 4T1,Eph41424,and JC.4T1 cells were divided into the 4T1 group(untransfected),the si-NC group(transfected with si-NC),the si-DNMT1 group(transfected with si-DNMT1),the si-DNMT1+anti-NC group(simultaneously transfected with si-DNMT1 and anti-NC),and the si-DNMT1+anti-miR-377-3p group(simultaneously transfected with si-DNMT1 and anti-miR-377-3p).qRT-PCR was used to detect the expression of circDNMT1 and miR-377-3p of 4T1 cells in each group;CCK-8 was used to detect the proliferation of 4T1 cells in each group;flow cytometry was used to detect the apoptosis of 4T1 cells in each group;Western blot was used to detect the expression of PUM1,EMT-related proteins and apoptosis-related proteins of 4T1 cells in each group;TargetScan website was used to predict the binding sites of miR-377-3p with circDNMT1 and PUM1;dual luciferase report was used to verify the targeting relationships of miR-377-3p with circDNMT1 and PUM1.After inoculation with 4T1 cells,BALB/c mice were randomly divided into the blank control group(injected with equal amount of normal saline),the negative control group(injected with si-NC via tail vein),the DNMT1 silencing group(injected with si-DNMT1 via tail vein),the combined control group(injected with si-DNMT1 and anti-NC via tail vein),and the combined silencing group(injected with si-DNMT1 and anti-miR-377-3p via tail vein),the tumor massess of mice were recorded and the morphological changes of tumors were observed by hematoxylin-eosin staining.Results circDNMT1 and PUM1 were up-regulated in TNBC tissues and cells,and miR-377-3p was down-regulated.The expression difference was most obvious in 4T1 cells,so 4T1 cells were selected for subsequent experiments.Compared with the 4T1 group and the si-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin protein of 4T1 cells in the si-DNMT1 group were significantly increased(P<0.05),the circ-DNMT1 level,the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression level of Bcl-2,N-cadherin,Vimentin protein were significantly decreased(P<0.05).Compared with the si-DNMT1 group and the si-DNMT1+anti-NC group,the expression of miR-377-3p,the apoptosis rate of 4T1 cells,the expression levels of Bax,cleaved caspase-3 and E-cadherin proteins of 4T1 cells in the si-DNMT1+anti-miR-377-3p group were significantly decreased(P<0.05),the expression level of PUM1 protein,OD values at 24 hours and 48 hours,the expression levels of Bcl-2,N-cadherin,Vimentin proteins were significantly increased(P<0.05).Compared with the miR-NC+WT-circDNMT1 group,the cell luciferase activity in the miR-377-3p mimic+WT-circDNMT1 group was significantly decreased(P<0.05);compared with the miR-NC+WT-PUM1 group,the cell luciferase activity in the miR-377-3p mimic+WT-PUM1 group was significantly decreased(P<0.05).The tumor cells in the blank control group and the negative control group were densely arranged with clear boundary;the tumor cells in the DNMT1 silencing group and the combined control group were loosely arranged,the nuclei were pyknotic,and the cell fragments were increased;the tumor cells in the combined silencing group were densely arranged and the boundaries tended to be clear.Compared with the blank control group and the negative control group,the tumor mass of mice in the DNMT1 silencing group was significantly decreased(P<0.05).Compared with the DNMT1 silencing group and the combined control group,the tumor mass of mice in the combined silencing group was significantly increased(P<0.05).Conclusion Silencing circDNMT1 may inhibit the expression of PUM1 by up-regulating miR-377-3p,thereby inhibiting the proliferation and EMT of TNBC cells,and promoting cell apoptosis.

Comparative study of UE and CDFI in distinguishing triple-negative breast cancer and fibroadenoma / 中国医学装备

Objective:To investigate the values of ultrasound elasticity(UE)imaging and color Doppler flow energy(CDFI)in differential diagnosis for triple negative breast cancer(TNBC)and fibroadenoma.Methods:A total of 50 TNBC patients who admitted to People's Hospital of Wanning from January 2021 to January 2022 and were confirmed by surgical pathology were selected,and they were divided into TNBC group.On the other hand,a total of 50 patients with fibroadenoma who were confirmed by surgical pathology during the same period were selected and they were divided into fibroadenoma group.All patients did not undergo any clinical intervention before ultrasound examination.UE and CDFI were used respectively to evaluate the degrees of softness and hardness of the tissues,the color blood flow and elasticity scores of lesions.The pathological result was used as the gold standard to analyze respectively the diagnostic efficacies of UE and CDFI for TNBC and fibroadenoma.Results:According to the characteristics of ultrasound imaging,the TNBC group mostly showed burr sign on lesion edge,the attenuation and hyperechoic halo of posterior echo,and existing axillary lymph node metastasis.The fibroadenoma group mostly showed clear boundaries of lesion area,regular lesion morphology,non-microcalcification.The diagnostic sensitivity,specificity and accuracy of UE detection were respectively 90.91%,82.14%and 86.00%,while these indicators of CDFI were respectively 73.08%,75.00%and 74.00%.In addition,the sensitivity,specificity and accuracy of the combined detection of them were respectively 94.23%,95.83%and 96.00%.The detection efficiency of the combined detection was higher than that of each single detection.Conclusion:UE has higher sensitivity in the differential diagnosis of TNBC and fibroadenoma,but it's specificity is not high.The combined detection of UE and CDFI can improve the specificity and accuracy of differential diagnosis.

Effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in knee osteoarthritis patients / 针灸推拿医学（英文版）

Objective:To observe the effects of warming triple needling plus Chinese medication on inflammatory responses and daily functioning ability in patients with knee osteoarthritis(KOA)due to wind-cold-dampness Bi-impediment. Methods:A total of 101 patients with KOA due to wind-cold-dampness Bi-impediment were divided into an acupuncture-medication group and a Chinese medication group using the random number table method.Fifty cases in the Chinese medication group took oral Fang Feng Xi Bi Tang for treatment,and 51 cases in the acupuncture-medication group received additional warming triple needling therapy.The symptom score of traditional Chinese medicine(TCM),inflammatory factor levels,and motor function of the knee joint were compared before and after treatment.The clinical efficacy was also compared between the two groups after treatment. Results:Three cases in the acupuncture-medication group and 2 cases in the Chinese medication group dropped out during the study,and the two groups each had 48 cases being included in statistical analysis ultimately.The total effective rate was 95.8%in the acupuncture-medication group,higher than 79.2%in the Chinese medication group,and the between-group difference was statistically significant(P<0.05).After treatment,the TCM symptom score dropped in both groups(P<0.05)and was lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The levels of interleukin(IL)-6,tumor necrosis factor(TNF)-α,and IL-1β dropped after the intervention in both groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05).The scores of knee pain intensity,knee joint stiffness,and diurnal functioning decreased after treatment in the two groups(P<0.05)and were lower in the acupuncture-medication group than in the Chinese medication group(P<0.05). Conclusion:Warming triple needling plus Fang Feng Xi Bi Tang can reduce inflammatory responses,improve daily functioning ability,and enhance the quality of life in patients with KOA due to wind-cold-dampness Bi-impediment.

Triple valve surgery in a patient with rheumatoid arthritis

@#Rheumatoid arthritis is a multisystem disorder that affects not only the musculoskeletal system but also other vital organ systems. This report tackles a case of a Filipino adult female with a 28-year history of rheumatoid arthritis on chronic DMARD and steroid use who developed symptoms of heart failure. This report will review the perioperative implications of a patient with rheumatoid arthritis for triple valve surgery.

AI Rudi's Experience in Treating Acne with Triple Chinese Medicinal Groups Combined with Chinese Medicinal Mask / 中医杂志

To summarize the clinical experience of Professor AI Rudi in treating acne with triple Chinese medicinal groups combined with Chinese medicinal mask. It is believed that the pathogenesis and treatment of male and female acne are different. The key mechanism of male acne is the dysfunction of the "lung-spleen and stomach-large intestine" axis， and the method of three jiao differentiation should be used. Clinically， the triple Chinese medicinal group， Rendongteng （Lonicera japonica） - Qishe （Portulaca oleracea） - Shicangpu （Acorus gramineus）， can scatter wind to relieve heat， and diffuse and disperse upper jiao； group Baihua Sheshecao （Scleromitrion diffusum） - Baixianpi （Dictamnus dasycarpus） - Tanxiang （Santalum album） can clear heat and drain dampness， and regulate middle jiao； group Huaimi （Styphnolobium japonicum） - Juemingzi （Senna tora） - Baizhu （Atractylodes macrocephala） can tonify and moisten to unblock the lower jiao. The core mechanism of female acne is the imbalance of the function of the "liver and kidney- Tiangui （reproduction-stimulating essence， corresponds with the tenth heavenly stem） - Chong and ren" axis， and the method of staged tratment based on menstrual cycle should be used. Before the menstrual period， group Tusizi （Cuscuta chinensis） - Yujing （Curcuma longa） - Qianghuoyu （Hansenia forbesii） can tonify kidney and relax liver； during the menstrual period， group Chuanxiong （Rhizoma Ligustici Chuangxiong） - Yimucao （Leonurus japonicus）- Cansha （Bombycis Faeces） can invigorate blood and regulate menstrual flow； after the menstrual period， group Huangjing （Polygonatum sibiricum） - Shanyurou （Corni Fructus） - Roucongrong （Cistanche deserticola） can nourish blood， assist yang and boost yin. Meanwhile， we attached importance to the internal and external treatment. Based on the internal administration of traditional Chinese medicine， Chinese medicinal masks were used for external application， commonly used in self-prescribed Xianglian Jinhuang Powder （香连金黄散） combined with Huoxue Powder （活血散） as the prescription for Chinese medicinal mask.

Correlation Analysis of Myelosuppression after Chemotherapy for Triple-Negative Breast Cancer and Its Prognosis / 中山大学学报(医学科学版)

ObjectiveTo investigate whether severe myelosuppression after chemotherapy is associated with prognosis in patients with breast cancer. MethodsTriple negative breast cancer （TNBC） patients who received chemotherapy at the Second Affiliated Hospital of Nanchang University from May 2， 2013 to May 2， 2018 were divided into a control group （no/mild myelosuppression） and a case group （severe myelosuppression）. In this study， 251 patients with TNBC met the inclusion and exclusion criteria， including 125 patients in the control group （20 patients with grade 0 myelosuppression， 43 patients with grade I myelosuppression， 62 patients with grade Ⅱ myelosuppression）， 126 patients in the case group （114 patients with grade Ⅲ myelosuppression， 12 patients with grade Ⅳ myelosuppression）. The general clinicopathological data of the patients in the two groups， including age， pathological type of tumor， tumor T stage， tumor N stage， tumor Nottingham grade， intravascular cancer thrombus， were analyzed using the χ2 test. The disease-free survival （DFS） and overall survival （OS） of the two groups were analyzed using the Kaplan-Meier method. A Cox proportional hazards regression model with multiple factors was used to analyze the impact of post-chemotherapy severe myelosuppression on disease-free survival （DFS） and overall survival （OS） in patients with TNBC. ResultsThe differences in general clinicopathologic data between the two groups of patients were not statistically significant （all P＞0.05）. The 5-year disease-free survival （DFS） rate was significantly lower in the control group compared with the case group （75.2% vs. 85.7%， P=0.027）. However， there was no statistically significant difference in the 5-year overall survival （OS） rate between the two groups （88.8% vs. 95.2%， P=0.057）. The analysis of the multifactorial Cox proportional hazards regression model revealed that post-chemotherapy severe myelosuppression was an independent protective factor for disease-free survival （DFS） （HR=0.332， 95% CI： 0.173-0.638， P=0.001） and overall survival （OS） （HR=0.193， 95% CI： 0.062-0.602， P=0.005） in TNBC patients. ConclusionOur results show that TNBC patients with severe myelosuppression after chemotherapy have longer disease-free survival （DFS） than those with no/mild myelosuppression， and overall survival （OS） also tend to be prolonged compared with those with no/mild myelosuppression， and severe myelosuppression after chemotherapy can be used as an independent predictor of a good prognosis in breast cancer.

Pharmacokinetics of Total Alkaloids of Corydalis saxicola in Depression Model Rats / 中国实验方剂学杂志

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg-1） and total alkaloids of C. saxicola group（210 mg·kg-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（tmax） and half-life（t1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC0-∞） of tetrahydropalmatine was the highest and the t1/2 was the shortest， and the AUC0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.