Mechanism of Key Ingredient of Astragalus membranaceus on Lung Adenocarcinoma via PI3K/AKT Signaling Clarified by Utilizing Network Pharmacology Approach and Experimental Validation / 中国结合医学杂志

OBJECTIVE@#To investigate the mechanism of the effect of Astragalus membranaceus (A. membranaceus) on lung adenocarcinoma at the molecular level to elucidate the specific targets according to the network pharmacology approach.@*METHODS@#The active components of A. membranaceus and their potential targets were collected from the Traditional Chinese Medicine Systems Pharmacology Database. Lung adenocarcinoma-associated genes were acquired based on GeneCards, Online Mendelian Inheritance in Man (OMIM), PharmGKB, and Therapeutic Targets databases. The PI3K/AKT signaling pathway-related genes were obtained using Reactome portal. Networks of "ingredient-target" and "ingredient-target-pathway-disease" were constructed using the Cytoscape3.6.0 software. The relationships among targets were analyzed according protein-protein interaction (PPI) network. Finally, molecular docking was applied to construct the binding conformation between active ingredients and core targets. Cell counting kit 8 (CCK8) and Western blot assays were performed to determine the mechanism of the key ingredient of A. membranaceus.@*RESULTS@#A total of 20 active components and their 329 targets, and 7,501 lung adenocarcinoma-related genes and 130 PI3K/AKT signaling pathway-related genes were obtained. According to Venn diagram and PPI network analysis, 2 mainly active ingredients, including kaempferol and quercetin, and 6 core targets, including TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR, were identified. The two important active ingredients of A. membranaceus, kaempferol and quercetin, exert the therapeutic effect in lung adenocarcinoma partly by acting on the 6 core targets (TP53, MAPK1, EGF, AKT1, ERBB2, and EGFR) of PI3K/AKT signaling pathway. Expressions of potential targets in lung adenocarcinoma and normal samples were analyzed by using UALCAN portal and found that ERBB2 was overexpressed in lung adenocarcinoma tissues and upregulation of it correlated with clinicopathological characteristics. Finally, quercetin repressed viabilities of lung adenocarcinoma cells by targeting ERBB2 on PI3K/AKT signaling confirmed by CCK8 and Western blot.@*CONCLUSION@#Our finding unraveled that an active ingredient of A. membranaceus, quercetin, significantly inhibited the lung adenocarcinoma cells proliferation by repressing ERBB2 level and inactivating the PI3K/AKT signaling pathway.

Paeoniflorin besylate relieves mice with antigen-induced experimental Sjogren's syndrome by regulating GRK2-JAK1-STAT1/2 signaling pathway / 中国药理学通报

Aim To observe the effect of CP-25 on the ESS mouse model and establish whether its effect is through regulating the binding of GRK2 to JAK1 and inhibiting the JAK1-STAT1/2-CXCL13 signaling pathway. Method We established ESS mouse model induced by SG protein, established into normal group, model group, CP-25 group with concentration of 35 mg • kg"1, 70 mg • kg"1, and HCQ group with concentration of 80 mg • kg"1. Mouse saliva flow was measured. The infiltration of lymphocyte in SG was observed by HE staining. The expression of p-JAKl, p- STAT1 and p-STAT2 in submandibular gland tissue was detected by Western blot. The level of CXCL13 in SG of mice was tested by IHC. GRK2 and JAK1 binding was determined by immunofluorescence and CO- IP. Results Compared with normal group, the saliva flow rate of ESS mice was low and lymphocytes were significantly infiltrated in the submandibular gland pathological sections. The CXCL13 protein level was highly expressed, which activated the JAK1-STAT1/2 signal. CP-25 significantly increased the salivary flow rate in ESS mice, reduced lymphocyte infiltration, improved pathological abnormalities, and inhibited the expression of JAK1-STAT 1/2 signaling and CXCL13. CP-25 significantly promoted the binding of GRK2 to JAK1. Conclusions CP-25 may inhibit the binding of GRK2 to JAK1, and then inhibit the activation of JAK1-STAT1/2-CXCL13 signaling pathway, improve the abnormal pathological manifestations of lymphocyte infiltration in submandibular gland, and improve the rate of saliva flow. CP-25 plays a therapeutic role in ESS mice.

PPV combined with internal limiting membrane tamponade and rat nerve growth factor injection in the treatment of large diameter IMH / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To observe the effect of pars plana vitrectomy(PPV)internal limiting membrane(ILM)insertion and nerve growth factor(NGF)injection in the treatment of large idiopathic macular hole(IMH). <p>METHODS: This was a retrospective clinical study which included 16 patients(16 eyes)with large IMH diagnosed in the Affiliated Eye Hospital of Nanjing Medical University from May 2018 to May 2020. All patients were treated with PPV combined with ILM insertion and NGF injection and the follow-up period was at least 6mo. Macular hole closure rates, best-corrected visual acuity(BCVA)(LogMAR), and optical coherence tomography(OCT)findings including ellipsoid zone(EZ)and external limiting membrane(ELM)were analyzed, the complications were also observed postoperatively.<p>RESULTS: The BCVA was 1.15±0.21 before operation, and the follow-up of BCVA was 1.02±0.19 and 0.87±0.24 respectively at 3 and 6mo after operation(<i>F</i>=34.966, <i>P</i><0.01); The BCVA was improved 3 and 6mo after operation(<i>P</i><0.01), and the BCVA at 6mo after operation was better than that at 3mo(<i>P</i><0.01). The closure rate of the MH was 100% and 11 eyes showed U-shaped closure in OCT(69%), 3 eyes were V-shaped closure(19%)and 2 eyes were irregular closure(13%). The BCVA of U-shaped closure group, V-shaped closure group and irregular closure group were 0.75±0.18, 1.1±0.19, and 1.20±0.00 respectively(<i>F</i>=6.937, <i>P</i><0.01). The recovery of BCVA in U-shaped closure group was significantly better than that in V-shaped closure group and irregular closure group(<i>P</i>=0.027, 0.007). Six months after operation, 10 eyes(91%)of ELM and 7 eyes(64%)of ellipsoid zone resumed continuity in U-shaped closure group, 2 eyes(67%)of ELM and 1 eye(33%)of resumed continuity in V-shaped closure group. ELM and ellipsoidal zone were not recovered continuously in irregular closure group(<i>P</i><0.05). During the follow-up period, we found no ocular or systemic complications.<p>CONCLUSION: PPV combined with ILM insertion and NGF injection is safe and effective in treating large IMH. The synergetic effect of NGF and ILM can obviously promote the closure of IMH, which is beneficial to the recovery of photoreceptor layer integrity and the improvement of visual function after operation.

The Influence of Serum Homocysteine Level to the Prognosis of Newly Diagnosed Multiple Myeloma Patients and Analysis of Related Factors / 中国实验血液学杂志

OBJECTIVE@#To analyze the influence of serum homocysteine (Hcy) levels to the prognosis of newly diagnosed multiple myeloma (MM) patients, and to explore related factors affecting the prognosis of the patients.@*METHODS@#The clinical pathological data of 180 newly diagnosed MM patients treated in our hospital from March 2013 to February 2015 were collected, and the patients were divided into high and low Hcy groups based on the median Hcy. The survival curves of the patients in the two groups were drawn to compare the differences of the survival; univariate and multivariate survival analysis was used to observe the influence of serum cysteine to the prognosis of newly diagnosed MM patients; the clinicopathological data of the patients with high and low Hcy in the two groups was compared, Pearson test was used to further analyzes the relationship between Hcy and different factors, and explores the related factors of Hcy affecting the prognosis of the patients.@*RESULTS@#The median survival times of patients in the high and low Hcy groups were 32 (5-59) and 41 (7-71) months, respectively. The 3-year survival rate of the patients in high Hcy group was significantly lower than those in low Hcy group, and the difference shows statistically significant (P<0.05). The results of univariate survival analysis showed that the OS of newly diagnosed MM patients whom with advanced age, high bone disease grade, high-level bone marrow plasma cell count, LDH, C-reactive protein, Cr, β@*CONCLUSION@#Serum Hcy level has a correlation trend with the survival of newly diagnosed MM, which is affected by factors such as Hb.

Clinical observation of heat-sensitive moxibustion treatment for coronavirus disease 2019 / 中国针灸

OBJECTIVE@#To observe clinical effect of heat-sensitive moxibustion on coronavirus disease 2019 (COVID-19) and to discusses the effective moxibustion treatment program.@*METHODS@#A total of 42 patients with COVID-19 (general type) were treated with heat-sensitive moxibustion at the acupoint area of Shenque (CV 8) and Tianshu (ST 25). The treatment was conducted under the standards of heat-sensitive moxibustion manipulation, which were "locating acupoint by feeling, moxibustion by differentiate sensation, dosage varies individually, ending after sufficient dosage". The incidence of after first heat-sensitive moxibustion, the reduction of negative emotions, the improvement of chest distress and impaired appetite, and the active acceptance rate of moxibustion before and after treatment were observed.@*RESULTS@#① The rate of heat-sensitive moxibustion for 20 min、40 min、1 h were respectively 52.4% (22/42), 90.5% (38/42), 100.0% (42/42). ② The incidences of feeling relaxed and comfortable immediately after the first, second, and third heat-sensitive moxibustion were 61.9% (26/42), 73.8% (31/42), and 92.9% (39/42), which were higher than 42.9% (18/42) before heat-sensitive moxibustion treatment (<0.05). ③ The incidences of chest distress after the first, second, and third heat-sensitive moxibustion were 23.8% (10/42), 16.7% (7/42), and 9.5% (4/42), which were lower than 50.0% (21/42) before heat-sensitive moxibustion treatment (<0.05); the incidences of impaired appetite after the first, second, and third heat-sensitive moxibustion were 26.2% (11/42), 19.0% (8/42), 9.5% (4/42), which were lower than 57.1% (24/42) before heat-sensitive moxibustion treatment (<0.05). ④ After the first treatment, the active acceptance rate of patients for heat-sensitive moxibustion was 100.0% (42/42), which was higher than 11.9% (5/42) before heat-sensitive moxibustion (<0.05).@*CONCLUSION@#The heat-sensitive moxibustion can effectively reduce the negative emotions and improve the symptoms of chest distress and impaired appetite with COVID-19. It is generally accepted by patients, and worthy of popularization and application in clinical treatment.

's experience in treating dry eye syndrome with fire needling / 中国针灸

Professor - is the representative inheritor of fire needling therapy. He proposed that the clinical application of fire needling is mainly based on pattern differentiation according to eight priciples, as well as in coordination with the theories of meridians and - organs. He believes that dry eye syndrome can be treated from the aspects of deficiency of liver and kidney, heart deficiency, and and deficiency. Through deeply digging the connotation of ancient classics, and combined his clinical practice using fire needling, professor created a unique therapy that select "Neichengqi"as the main acupoint combined with Xialeidian, Dagukong (EX-UE 5), Xiaogukong (EX-UE 6) and Shaoze (SI 1) in the treatment of dry eye syndrome. In this paper, from the etiology and pathogenesis of dry eye syndrome and therapeutic characteristics of fire needling, the thoughts of syndrome differentiation and characteristics of acupoints selection of professor were analyzed by a typical case, and it is expect to enrich the clinical treatment plan for dry eye syndrome.

Discussion on professor SHAO Jing-Ming's academic opinion of focusing spirit / 中国针灸

During professor SHAO Jing-ming's academic research and medical practice, his academic opinion of focusing spirit is gradually developed. In terms of nurturing the spirit, attention should be paid on persistence as well as everyday health maintenance and exercise to nurture the spirit of physician. In terms of clinical diagnosis and treatment, patients' psychology, employment and life status should be observed and experienced, which could bring more methods to take essential care of patients' spirit. The treatment should work with psychological counseling, advocating that based on patients' qi and spirit, various forms of treatment methods should be properly used, such as acupuncture or moxibustion or combination of acupuncture and medicine, along with simple acupoint selection and harmony medication. Before clinical treatment of acupuncture, calming the mind is critically emphasized to make a clear diagnosis. During the acupuncture, calming and focusing the mind is necessary as well as emphasizing the details, so acupuncture could be integrated with Chi Gong to create a new warming-sensation technique. In a word, the academic opinion of focusing spirit is shedding an inspiring light upon further study.

Research and practice on basic skill training and technique improving of acupuncture and tuina major / 中国针灸

In order to summarize and perfect the basic skill practicing method in acupuncture teaching and form a characteristic teaching, the research on skill training and technique improving of acupuncture and tuina major was carried out. The undergraduate students in acupuncture and tuina major from College of Acupuncture-Moxibustion and Tuina were randomly divided into an experimental group and a control group. Students from both groups received the basic courses of acupuncture-moxibustion and tuina as requested in the syllabus and the special teaching was added to the experimental group, namely "three practice" (strength practice, coordination practice, targeted practice of acupuncture basic skills) and "three enlightenment" (technique enlightenment, mind and qi enlightenment, efficacy enlightenment). During and after the courses, the teaching effectiveness was evaluated on the basis of needling manipulation. The peacetime score in the experimental group was superior to that in the control group (38.03 +/- 1.14 vs 33.25 +/- 1.31, P < 0.05), the total score in the experimental group was superior to that in the control group (84.03 +/- 6.30 vs 78.05 +/- 6.55, P < 0.05). The special teaching method of "three practice" and "three enlightenment" can improve the effect of skill training teaching method. It highlights the unique feature of central plains by integrating the essence of Shaolin internal qigong and Chen-style Taiji, it can also provide new ideas for the practical teaching of TCM professional courses and the construction of characteristic professionals.

Design and application of hand-wrist caring moxibustion box / 中国针灸

A hand-wrist moxibustion box is designed to effectively solve difficulty to have moxibustion at handwrist joint and problem of bad moxibustion effect as well as improve heat efficiency of moxibustion. The device is consisted of a box and protective screening. The box is hollow with opening on top and bottom. A reversible cover is fixed on the top of the box and support frames are put in the inner-middle. On the side wall there is a hole that is at the same horizontal level of support frames, and horizontal protective screening is put on the bottom. The design of this moxibustion box is novel and unique, simple and reasonable, which could give moxibustion on hand and wrist at the same time. Also it is easily made with low cost, easy to use and favorable effect. It is an innovation on moxibustion box.

Ultra-high cycle fatigue behaviors of implanted Ti-6Al-4V in high frequency after subjection to simulated body fluid / 医用生物力学

Objective To study the ultra-high cycle fatigue behaviors of the Ti-6Al-4V alloy implant after subjection to simulated body fluid (SBF) environment exceeding 107 cycles, and to predict its service life. Method The Ti-6Al-4V alloy specimens were subjected to SBF in two groups for two days and six days respectively; using the ultrasonic fatigue testing technique, the ultra high cycle fatigue properties of Ti-6Al-4V alloy after subjection to SBF in body temperature were studied and the initiation mechanisms of fatigue cracks were investigated and analyzed with scanning electron microscopy (SEM) and energy dispersive atomic X-ray (EDA X ray). Then, a comparison with corresponding behaviors of the normal Ti 6Al 4V alloy was made. Results The S~N curve of the Ti-6Al-4V alloy after subjection had the similar tendency as that of the normal one, showing that they descended continuously during 104 and 108 cycles and the descending tendency was lower in the region of 107～108 cycles; the life of the specimens after subjection dropped before the fatigue life of 107 cycles and was smaller after the fatigue life of 107 cycles than that of the normal ones; the life of the specimens subjected for six days had little difference with that subjected for two days; fracture could still occur beyond 107 cycles, showing that there was no fatigue limit as the traditional fatigue conception described. Fatigue cracks mainly initiated from the surface of specimen before the fatigue life of 107 cycles and some specimens had multiple crack initiation sites; fatigue failure initiated from internal inclusion where mostly the element Al aggregated after the fatigue life of 108 cycles. Conclusions The ultra high cycle fatigue properties of the Ti-6Al-4V alloy decreas a little with SBF subjection; the initiation site of the fatigue crack changes from the surface to the internal defect with the increase of the number of cycle.

Comparison of detecting heat-sensitive condition of Neiguan (PC 6) in heart-qi deficiency patients with moxibustion sensation and with infrared / 中国针灸

<p><b>OBJECTIVE</b>To compare the method of detecting heat-sensitive (HS) condition of Neiguan (PC 6) with moxibustion sensation and with infrared in heart-qi deficiency patients (HQD), and to find an objective detection method for HS condition of acupoints.</p><p><b>METHODS</b>The study was performed on 74 HQD patients. Take infrared thermograph of the tested skin area in natural state. Then thermosensitive test was taken after infrared thermograph acquisition (suspended moxibustion for 10 min). After moxibustion infrared radiometry was implemented for the second time. The infrared radiation information of the forearms was collected and the major axis of the moxibustion reaction area was recorded. The effect of moxibustion sensation and infrared detection on HS Neiguan (PC 6) in HQD patients was compared.</p><p><b>RESULTS</b>When the Neiguan (PC 6) in HQD patients was on HS condition, most of the infrared intensity was high temperature and compared with moxibustion sensation method, the sensitivity was 66.7%, the specificity 76.9%, and the accuracy 70.3%. After moxibustion on the HS Neiguan (PC 6) area, the infrared intensity diffused longitudinally along inner side of forearms. Compared with the result of the moxibustion sensation method, its sensitivity was 87.5%, the specificity 92.3%, and the accuracy 89.2%.</p><p><b>CONCLUSION</b>(1) The state of HS condition of Neiguan (PC 6) in HQD patients could be detected objectively by infrared radiation. (2) After moxibustion, the HS condition of acupoints produced thermal phenomena as thermal expansion, heat transfer, which could be demonstated objectively by the infrared radiation image as well as the sensation of subjects.</p>

Multiple central clinical studies on the needling method for regulating wei and strengthening brain for treatment of insomnia / 中国针灸

<p><b>OBJECTIVE</b>To observe the clinical therapeutic effect of the needling method for regulating wei and strengthening brain on insomnia.</p><p><b>METHODS</b>Two hundred cases of insomnia were randomly divided into a test group and a control group, 100 cases in each group. The test group were treated with the needling method for regulating wei and strengthening brain with Baihui (GV 20), Dazhui (GV 14), Shenmai (BL 62), Zhaohai (KI 6) and ear points Yuanzhong, Shenmen selected; and in the control group, Sishencong (EX-HN 1), Shenmen (HT 7) and Sanyinjiao (SP 6) were selected. Acupuncture was given once daily for 15 days. Pittsburgh sleep quality index (PSQI) was used for scoring before and after treatment.</p><p><b>RESULTS</b>The total effective rate was 89.0% in the test group and 65.0% in the control group with a very significant difference between the two groups (P<0.01); the difference of PSQI scores before and after was -9.15+/-5.68 in the test group and -5.64+/-5.73 in the control group, with a very significant difference before and after treatment in the two groups (P<0.01).</p><p><b>CONCLUSION</b>The therapeutic effect of the needling method for regulating wei and strengthening brain on insomnia is better than that of normal needling method.</p>

Effects of acupuncture at "Sishencong" (EX-HN 1) on physiological functions in the sleep disorder model mouse / 中国针灸

<p><b>OBJECTIVE</b>To probe into the effect of acupuncture at "Sishencong" (EX-HN 1) on sleep and the mechanism.</p><p><b>METHODS</b>Forty-eight white mice were randomly divided into a Sishencong group, a Zusanli group, a model group and a blank control group, 12 mice in each group. In the mice of the first 3 groups, sleep rhythm disorders was induced by repeatedly regular intraperitoneal injection of small dose of Caffeine, and the mice of the first two groups were treated by acupuncture at "Sishencong" (EX-HN 1) and "Zusanli" (ST 36), respectively. Living state and, circadian activities were observed, and nitric oxide synthase (NOS) activity and nitric oxide(NO) content in the brain were detected.</p><p><b>RESULTS</b>Acupuncture at "Sishencong" (EX-HN 1) or "Zusanli" (ST 36) could significantly increase NOS activity and NO content in the brain, with acupuncture at "Sishencong" (EX-HN 1) being significantly better than acupuncture at "Zusanli" (ST 36) (P < 0.01).</p><p><b>CONCLUSION</b>Acupuncture at Sishencong (EX-HN 1) treats insomnia and regulates sleep and many mental and nervous symptoms, which are carried out partially through increasing NOS activity and NO content, promoting normal function of brain tissues.</p>

Study on professor Shao Jing-ming's academic thought / 中国针灸

Professor Shao Jing-ming has been engaged in medicine for over 70 years. He has original academic view in diagnosis of diseases, prescription of combined acupoints, needling manipulation and combination of acupuncture and moxibustion with medication, etc.. He holds that disease should be combined with syndrome, modern medical sciences are used for definite diagnosis of diseases; for acupoint prescriptions, fewer and better acupoints are selected, and treatment of difficult and complicated diseases with back-shu points usually can attain good results; correct application of needling manipulation and Deqi is the key of therapeutic effects; he creates and uses heat-sensation needling manipulation, the method of twirling-inserting needle with finger pressure, injection-type inserting needle method; combination of acupuncture-moxibustion with medicine can increase therapeutic effects. He writes a book Zhongyi Zhiyao of about 300,000 words.

Contributions of Yang Ji-zhou to moxibustion methods / 中国针灸

YANG Ji-zhou, a famous scientist of acupuncture and moxibustion in the Ming Dynasty. He was a great master not only in manipulation methods of acupuncture, but also in moxibustion therapy, with unique and profound deep cognition. His main contributions include the three aspects: (1) collected a great deal of methods and experience of moxibustion treatment from moxibustion physicians and gathered and mustered a great works about moxibustion methods before the Ming Dynasty; (2) combined with his own clinical experiences, systematized the methods and techniques of moxibustion, including the relationship between posture and point-fathoming, the treatment orders, the size of moxa cone, the number of moxa cones, the techniques of burning moxa, the methods for vesiculation moxibustion, etc. forming a more systematic manipulation standard; (3) invented and formed YANG's characteristics of clinical moxibustion treatment, i. e selecting a few points to dredge the meridian-qi, grasping opportunity of moxibustion, combining acupuncture and moxibustion with medicine, and consolidating the therapeutic effect by proper diet after treatment.

Affection of metallothionein-3 to dUTPase's accommodating cellular toxicity of dUTP / 生物工程学报

Metallothionein-3 (MT-3), renamed as growth inhibitory factor (GIF), is a brain specific member of the metallothionein family. Human dUTPase is a recently found protein in brain that can interact with hMT-3. They have the growth inhibitory activity on neuron cell by interaction. To study the affection of hMT-3 to dUTPase's eliminating the cellular toxicity caused by dUTP, the pSVHA-dUTPase and pFLag-hMT-3 genes have been transfected into HEK293 cells. In addition, the dUTPase and hMT-3 proteins were expressed in BL21 to study the role of hMT-3 on the hydrolyzation of dUTP by dUTPase. The results demonstrate that the cells co-transfected with dUTPase and hMT-3 genes have more strong resistibility to dUTP than the cells transfected only with dUTPase gene. And that the hMT-3 protein can accelerate the hydrolyzation of dUTP by dUTPase. All these indicate that hMT-3 can cooperate with dUTPase to protect better the 293 cells from dUTP. This research offered the theoretic elements for the application of hMT-3 and dUTPase in chemic cure.

Studies on Extraction of Icariin in Herba Epimedii / 中药新药与临床药理

Objective To optimize the extraction process for icariin from Herba Epimedii. Methods The content of icariin in the extracts obtained by different extraction methods was determined with HPLC. The effect of solvents, boiling time, extracting time and temperature, and the size of the medicinal powder was observed. Results Different extraction methods had great influence on the extraction rate of icariin. Conclusion This research can provide evidence for the extraction of active component from Herba Epimedii in industrial production.