Alcohol extract of root and root bark of Toddalia asiatica alleviates CIA in rats through anti-inflammatory and proapoptotic effects / 中国中药杂志

This study aims to investigate the therapeutic effect of alcohol extract of root and root bark of Toddalia asiatica(TAAE) on collagen-induced arthritis(CIA) in rats through phosphatidylinoinosidine-3 kinase/protein kinase B(PI3K/Akt) signaling pathway. To be specific, CIA was induced in rats, and then the rats were treated(oral, daily) with TAAE and Tripterygium Glycoside Tablets(TGT), respectively. The swelling degree of the hind leg joints was scored weekly. After 35 days of administration, the histopathological changes were observed based on hematoxylin and eosin(HE) staining. Enzyme-linked immunosorbent assay(ELISA) was employed to detect the levels of cytokines [tumor necrosis factor-α(TNF-α), interleukin(IL)-6)]. Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL) staining was performed to detect the apoptosis of synoviocytes in rats. Western blot was used to detect the expression levels of apoptosis-related proteins B-cell lymphoma 2(Bcl-2)-associated X(Bax), Bcl-2, and caspase-3 and pathway-related proteins phosphoinositide 3-kinase(PI3K), phosphorylated(p)-PI3K, protein kinase B(Akt), and p-Akt. RT-qPCR was conducted to examine the mRNA levels of Bax, Bcl-2, caspase-3, TNF-α, IL-6, and IL-1β and pathway-related proteins PI3K, p-PI3K, Akt, and p-Akt. TAAE can alleviate the joint swelling in CIA rats, reduce serum levels of inflammatory cytokines, improve synovial histopathological changes, promote apoptosis of synoviocytes, and inhibit synovial inflammation. In addition, RT-qPCR and Western blot results showed that TAAE up-regulated the level of Bax, down-regulated the level of Bcl-2, and activated caspase-3 to promote apoptosis in synoviocytes. TAAE effectively down-regulated the protein levels of p-PI3K and p-Akt. In this study, TAAE shows therapeutic effect on CIA in rats and reduces the inflammation. The mechanism is that it suppresses PI3K/Akt signaling pathway and promotes synoviocyte apoptosis. Overall, this study provides a new clue for the research on the anti-inflammatory mechanism of TAAE and lays a theoretical basis for the better clinical application of TAAE in the treatment of inflammatory and autoimmune diseases.

Causes of False-Positive Results in 68Ga-Labeled Fibroblast Activation Protein Inhibitor PET/CT Imaging / 中国医学科学院学报

Objective To investigate the causes of false-positive results in the 68Ga-labeled fibroblast activation protein inhibitor (68Ga-FAPI-04) PET/CT imaging. Methods The imaging data of 547 patients undergoing 68Ga-FAPI-04 PET/CT examination in the Department of Nuclear Medicine of the Affiliated Hospital of Southwest Medical University from September 2020 to May 2021 were retrospectively collected.Two experienced nuclear medicine diagnostic physicians analyzed the clinical data,relevant imaging examinations,laboratory examinations,pathological results and follow-up results of the patients with false-positive results. Results The 68Ga-FAPI-04 PET/CT imaging of 547 patients showed false-positive results in 99 (18.1%) patients,including 56 males and 43 females.The postoperative pathological examination confirmed false-positive results in 13 patients,including 1 patient of thyroiditis,2 patients of pulmonary tuberculosis,1 patient of bone tuberculosis,2 patients of pulmonary inflammatory pseudotumor,1 patient of pulmonary sarcoidosis,1 patient of pulmonary benign fibroma,1 patient of organic pneumonia,2 patients of renal angiomyolipoma,1 patient of mass pancreatitis,and 1 patient of pancreatic mucinous cystadenoma.The medical history,relevant imaging examination,and long-term follow-up confirmed false-positive results in 86 patients.Specifically,the false-positive uptake in the neck,chest,abdomen,bone joint,and skin occurred in 8 (9.3%),13 (15.1%),5 (5.8%),57 (66.3%),and 3 (3.5%) patients,respectively.Inflammation-related uptake appeared in 83 (83.8%) patients with false-positive imaging results,of which arthritis (23 patients) and osteophyte (29 patients) were the most common.Sixteen (16.2%) patients showed the false-positive uptake related to fibroblasts. Conclusion 68Ga-FAPI-04 PET/CT imaging will show non-malignant tumor false-positive results,which are mainly associated with inflammation and fibroblasts.

Impact of the Coronavirus Disease 2019 Pandemic on Pediatric Gastrointestinal Endoscopy:A Questionnaire-based Internet Survey of 162 Institutional Experiences in Asia Pacific / 대한소아소화기영양학회지

Purpose@#The impact of coronavirus 2019 (COVID-19) on gastrointestinal (GI) endoscopy procedures in adults has been reported, with a drastic reduction in the number of procedures.However, there are no sufficient data regarding the impact on pediatric GI endoscopy. Here, we aimed to report that impact in the Asia-Pacific region. @*Methods@#A questionnaire-based internet survey was conducted from June to November 2021 among pediatric endoscopy institutions in the Asia-Pacific region, with each institution providing a single response. Overall, 25 questions focused on the impact of the number of procedures conducted, the usage of personal protective equipment (PPE), and endoscopy training programs during the pandemic. @*Results@#A total of 162 institutions across 13 countries in the Asia-Pacific region participated in the study, and 133 (82.1%) institutions underwent procedure changes since the emergence of COVID-19. The number of esophagogastroduodenoscopy and ileocolonoscopy procedures decreased in 118/133 (88.7%) and 112/133 (84.2%) institutions, respectively. Endoscopy for patient with positive COVID-19 in an emergency or urgent cases still carried out in 102/162 (62.9%) institutions. Screening of COVID-19 for all patients before endoscopy was done across 110/162 (67.9%) institutions. PPE recommendations varied among institutions.Pediatric gastrointestinal endoscopy training programs were discontinued in 127/162 (78.4%) institutions. @*Conclusion@#This study reports the impact of the COVID-19 pandemic on pediatric gastrointestinal endoscopy in the Asia-Pacific region. There has been a significant reduction in the number of endoscopic procedures and relevant training programs.

Proton Pump Inhibitor-unresponsive Laryngeal Symptoms Are Associated With Psychological Comorbidities and Sleep Disturbance: A Manometry and Impedance-pH Monitoring Study

Background/Aims@#Laryngeal symptoms are largely treated with empiric proton pump inhibitor (PPI) therapy if no apparent pathology shown on ear, nose, and throat evaluation and reflux-related etiologies are suspected. However, treatment response remains unsatisfactory. This study aimed to investigate the clinical and physiological characteristics of patients with PPI-refractory laryngeal symptoms. @*Methods@#Patients with persistent laryngeal symptoms despite PPI treatment for ≥ 8 weeks were recruited. A multidisciplinary evaluationcomprising validated questionnaires for laryngeal symptoms (reflux symptom index [RSI]), gastroesophageal reflux disease symptoms, psychological comorbidity (5-item brief symptom rating scale [BSRS-5]) and sleep disturbance (Pittsburgh sleep quality index [PSQI]), esophagogastroduodenoscopy, ambulatory impedance-pH monitoring, and high-resolution impedance manometry were performed.Healthy asymptomatic individuals were also recruited for comparison of psychological morbidity and sleep disturbances. @*Results@#Ninety-seven adult patients and 48 healthy volunteers were analyzed. The patients had markedly higher prevalence of psychological distress (52.6% vs 2.1%, P < 0.001) and sleep disturbance (82.5% vs 37.5%, P < 0.001) than the healthy volunteers. There were significant correlations between RSI and BSRS-5 scores, and between RSI and PSQI scores (r = 0.26, P = 0.010, and r = 0.29, P = 0.004, respectively). Fifty-eight patients had concurrent gastroesophageal reflux disease symptoms. They had more prominent sleep disturbances (89.7% vs 71.8%, P < 0.001) than those with laryngeal symptoms alone but similar reflux profiles and esophageal motility. @*Conclusions@#PPI-refractory laryngeal symptoms are mostly associated with psychological comorbidities and sleep disturbances. Recognition of these psychosocial comorbidities may help optimize management in these patients.

Effect of Toddalia asiatica Alcohol Extract on Apoptosis of Non-small Cell Lung Cancer A549 Cells Based on Autophagy Pathway / 中国实验方剂学杂志

ObjectiveTo study the effects of Toddalia asiatica alcohol extract on autophagy and apoptosis of non-small cell lung cancer A549 cells， and to explore its possible mechanism. MethodA549 cells were cultured in vitro. Cell counting kit-8 （CCK-8） was used to detect the proliferation of A549 cells， and cell survival rate was calculated to screen the drug concentration. The apoptosis in each dose group and that after the use of 3-methyladenine （3-MA）， an autophagy inhibitor， were detected by flow cytometry combined with Annexin V-FITC/PI double staining. Western blot was used to detect the expression levels of apoptosis-related proteins such as B cell lymphocytoma-2（Bcl-2）， Bcl-2-associated X protein（Bax）， microtubule-associated protein 1 light chain 3 （LC3）， cleaved cysteinyl aspartate-specific protease-3 （cleaved Caspase-3）， activated poly （Adenosine diphosphate） ribonucleotide polymerase （cleaved PARP1）， PARP1， activated death activator （t-Bid）， Bid， and ubiquitin-binding protein p62 in each group and those after the use of 3-MA. ResultCompared with the conditions in the control group， the cell survival rate in 0.25 g·L-1 group （P<0.05）， and 0.5， 1， 2， 4 g·L-1 groups （P<0.01） was decreased after 24 h intervention. Additionally， the cell survival rate was reduced in a concentration-dependent manner at 48 h and it was less than 10% at 4 g·L-1 （P<0.01）. Compared with the conditions in the control group， the total apoptosis rate in 0.5 g·L-1 group was increased （P<0.05）， and the apoptosis rate in 1 and 2 g·L-1 groups was also increased （P<0.01）. Compared with the 2 g·L-1 group and 3-MA group， the 3-MA combined with T. asiatica alcohol extract had significantly decreased apoptosis rate （P<0.01）. Compared with the conditions in the control group， elevated expression of pro-apoptotic proteins cleaved PARP1， Bax and t-Bid in 1 and 2 g·L-1 groups （P<0.05， P<0.01）， and reduced expression of Bid in the 2 g·L-1 group （P<0.01） were found. Compared with the conditions in the control group， the expression of anti-apoptotic protein Bcl-2 （P<0.05， P<0.01） and the level of p62 （P<0.01） were down-regulated in 0.5， 1， 2 g·L-1 groups， while the level of LC3 Ⅱ protein was up-regulated （P<0.01）， with certain concentration dependence. ConclusionT. asiatica alcohol extract could significantly inhibit the proliferation of A549 cells， which might be related to promoting autophagy and inducing apoptosis.

Comparison of clinical efficacy effect between anisometropia amblyopia and strabismus amblyopia / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To compare the effect of comprehensive treatment in children with anisometropia and strabismus amblyopia.<p>METHODS: Prospective study. Forty-six individuals(mean age 9±3 years old, 26 males, 20 females)with previously untreated monocular amblyopia were recruited in our hospital from July 2018 to January 2020. There were 23 patients with strabismus monocular amblyopia(mean age 9±3 years old, 12 males, 11 females)and 23 patients with anisometropia monocular amblyopia(mean age 9±3 years old, 14 males, 9 females). The best corrected visual acuity(Tumbling E Chart)and stereopsis(Titmus)were measured before and after a 6mo period of comprehensive treatment(refractive correction, patching and precision eyesight training). The differences of monocular visual benefits(visual acuity)and binocular visual benefits(stereopsis)between two groups before and after treatment were compared. <p>RESULTS: Before treatment, there was no significant difference of best corrected visual acuity between anisometropia amblyopia and strabismus amblyopia(<i>t</i>= -0.475, <i>P</i>>0.05), but the stereopsis of strabismus amblyopia was significantly lower than that of anisometropia amblyopia(<i>t</i>= -3.919, <i>P</i><0.001). After 2mo treatment, there was a significant difference in best corrected visual acuity benefits between anisometropia amblyopia and strabismus amblyopia(<i>t</i>= -2.946, <i>P</i><0.01), but there was no significant difference in stereopsis benefits between anisometropia amblyopia and strabismus amblyopia(<i>t</i>=1.305, <i>P</i>>0.05). After 6mo treatment, there was a significant difference in visual acuity benefits between anisometropia amblyopia and strabismus amblyopia(<i>t</i>= -2.353, <i>P</i><0.05), and there was also a significant difference in stereopsis benefits between anisometropia amblyopia and strabismus amblyopia(<i>t</i>=2.218, <i>P</i><0.05). However, the stereopsis of strabismus amblyopia was still lower than that of anisometropia amblyopia at 6mo(<i>t</i>=-2.760, <i>P</i><0.01).<p>CONCLUSION: We conclude that the stereopsis of patients with strabismus amblyopia is more severe than those with anisometropic amblyopia before treatment under the same visual acuity. The visual acuity of patients with anisometropic amblyopia recovers faster than patients with strabismus amblyopia through treatment. While the stereopsis of patients with strabismus amblyopia recovers faster than patients with anisometropic amblyopia, but the level of stereopsis with strabismus amblyopia is still lower than that of patients with anisometropic amblyopia.

Evaluation of the effect of 2-aminoethoxydiphenyl-borate on cardiac dysfunction in arsenic poisoning rats by stratified strain technique / 中华超声影像学杂志

Objective:To evaluate the effect of 2-aminoethoxydiphenyl-borate (2-APB) on cardiac dysfunction in arsenic poisoning rats by stratified strain technique.Methods:Thirty-two 12-week-old SD rats were randomly divided into control group ( n=8) and arsenic exposure group ( n=24). After 12 weeks of arsenic exposure, arsenic exposure group was divided into three groups: natural recovery group ( n=8), low-dose intervention group (n=8) and high-dose intervention group ( n=8). The rats were treated with 2-APB for 21 days. After the last administration, the routine parameters and the layered strain parameters were measured by ultrasonic instrument. Then the rats were killed and their blood and myocardial samples were obtained. The levels of serum creatine kinase isoenzyme (CK-MB) and lactate dehydrogenase (LDH) were tested, and the morphological changes of cardiomyocytes were observed by HE staining. Results:Left ventricular ejection fraction (LVEF), left ventricular short axis shortening (LVFS), global circumferential strain of subendocardial myocardium (GCS-endo), global circumferential strain of middle myocardium (GCS-mid), global circumferential strain of subepicardial myocardium (GCS-epi) and circumferential strain rate of left ventricular segments (SrC) in the natural recovery group were lower than those in the control group ( P<0.05), while serum CK-MB and LDH were higher than those in the control group ( P<0.05). Some ultrasonic parameters and biochemical indexes in the low and high dose intervention groups were improved in varying degrees compared with the natural recovery group ( P<0.05). The correlation between GCS-endo and CK-MB was the highest ( r=-0.931, P<0.05). Myocardial HE staining showed that the degree of myocardial cell swelling and necrosis were reduced, and erythrocyte exudation was reduced in the low and high dose intervention groups compared with the natural recovery group. Conclusions:The stratified strain technique can be used to evaluate the protective effect of 2-APB on cardiac dysfunction in arsenic poisoning rats, and GCS-endo may be one of its sensitive indexes.

Chinese Herbal Medicines Prevent and Treat Atopic Dermatitis by Improving Skin Barrier： A Review / 中国实验方剂学杂志

Atopic dermatitis is a chronic， refractory and inflammatory skin disease with the clinical manifestations of severe pruritus and recurrent attacks. It has a high incidence and is closely correlated with other allergic， autoimmune or infectious diseases， which can cause a variety of secondary diseases and mental and psychological disorders， seriously affecting the life quality of patients. Chinese herbal medicines have been used for the prevention and treatment of atopic dermatitis for thousands of years， and many Chinese herbal medicines （including compound prescriptions） effective for this disease have been recorded. These medicines generally have little adverse reactions and the treated patients have low recurrence rate of atopic dermatitis. According to the evidence of modern medicine， the onset of atopic dermatitis is related to the impairment of skin barrier function， abnormal immune response， and abnormal differentiation of mast cells， antigen-presenting cells， and eosinophils. Additionally， it is associated with mental， endocrine， metabolic and other factors. The defect of skin barrier function and the dysfunction of immune system are the main pathogenesis of atopic dermatitis. In recent years， scientists have achieved certain progress in improving skin barrier function with Chinese herbal medicines. This paper systematically summarizes the studies about the application of Chinese herbal medicines in regulating the expression of epidermal proteins， epidermal lipids， aquaporins， tight junction proteins， and antimicrobial peptides in recent 10 years， aiming to clarify the pathological mechanism and provide reference for the clinical research and application of Chinese herbal medicines in the treatment of atopic dermatitis.

Prevention and Treatment of Atopic Dermatitis with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Atopic dermatitis （AD） is a chronic， recurrent and inflammatory skin disease. Modern medical research suggests that AD is related to immune function， genes， skin barrier and other factors， while the specific etiology and pathogenesis remains unclear. The disease has a long course and is prone to reoccur， which seriously affects people’s production and life. Steroids， antihistamines and immunosuppressants are commonly used western medicines for the treatment of AD， which， however， will cause adverse reactions after long-term application. Traditional Chinese medicine （TCM） has a long history， good therapeutic effect and rich clinical experience in the prevention and treatment of AD， and the research on the treatment of AD with TCM has been intensifying. Centering on the theory of TCM， we systematically summarized the research progress related to AD， discussed the etiology and pathogenesis of AD， and summarized the TCM syndrome differentiation of AD from the aspects of eight principles， etiology， Qi-blood-body fluid， zang-fu organs， six meridians， defense-Qi-nutrient-blood and triple energizer. According to the etiology and pathogenesis of AD， we proposed the therapeutic regimens corresponding to the type and stage of the disease. Considering the research progress achieved in the recent years in the prevention and treatment of AD by TCM and the modern pharmacological research on Chinese medicinal materials， we reviewed the classic famous prescriptions， self-made prescriptions and Chinese patent medicines， and expounded the mechanisms of single Chinese medicinal materials in the treatment of AD at the molecular level. The TCM external therapies such as wet compress， medicated bath， gel and ointment are safe and effective. Acupuncture and moxibustion play a role in the prevention and treatment of AD， which is worthy of promotion in clinical practice， and the syndrome differentiation methods of Qi-blood-body fluid and triple energizer are novel in the treatment of this disease. TCM， characterized by diverse therapeutic methods and good clinical efficacy， is worthy of promotion in the treatment of AD， which will contribute to the development of TCM in China.

Therapeutic Drug Monitoring of Biologics for Patients with Inflammatory Bowel Diseases: How, When, and for Whom?

During the past decade, we have entered an era of biologics for the treatment of Crohn’s disease and ulcerative colitis. The therapeutic goal of inflammatory bowel disease (IBD) management has evolved from symptom control and clinical remission to mucosal healing or even deep remission. Histological remission for ulcerative colitis and transmural healing of Crohn’s disease are potential future goals. With the adoption of the treat-to-target concept, and given the need for tight control of IBD activity, therapeutic drug monitoring (TDM) is an important element of precision medicine. TDM involves the measurement of serum biologics and anti-drug antibodies levels, to confirm whether the right drug with the right dosage was prescribed to reach the right serum levels. TDM may help clinicians adjust biologics based on objective biomarkers instead of using empirical dosage escalation or making symptom-based therapeutic adjustments. Wellestablished reactive TDM algorithms have been proposed, and emerging evidence supports the clinical application of a proactive TDM strategy to enhance the duration of effective biologics and improve clinical outcomes. Recently, the proactive TDM strategy was shown to avoid the secondary loss of response to biologics, and improve long-term clinical outcomes in IBD patients. This review summarizes data from trials, and practice guidelines, on the clinical application of proactive and reactive TDM strategies for the daily care of biologic-treated IBD patients.

Value of high resolution magnetic resonance imaging for preoperative evaluation of Denonvilliers fascia in patients with rectal cancer / 中华胃肠外科杂志

Objective: Total mesorectal excision (TME) is the gold standard for surgical treatment of mid-low rectal cancer, but the postoperative incidence of urination and sexual dysfunction is relatively high. Preserving the Denonvilliers fascia (DF) during TME can reduce the postoperative incidence of urination and sexual dysfunction. In this study, high resolution magnetic resonance imaging (MRI) was used to observe the imaging performance and display of DF, so as to determine the value of this technique in preoperative evaluation of the preservation of DF. Methods: A descriptive cohort study was carried out. Clinical data of patients with rectal cancer who underwent TME and received preoperative high-resolution MRI at department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University from August 2015 to June 2017 were retrospectively analyzed. The characteristics of DF were examined, and the shortest distance (d) between the anterior edge of tumor and DF was measured on high-resolution MRI. The distance d was compared between patients with stage T1-T2 and those with stage T3. Receiver operating characteristic (ROC) analysis was used to determine the predictive value of d for stage T1-T2 disease. Results: Thirty-two patients were enrolled in the study, including 27 males and 5 females with mean age of (62.9±8.9) years. DF was visualized in 96.9% (31/32) of cases on the T2WI sequence. The mean distance d in patients with stage T1-T2 disease (n=23) was (6.73±2.65) mm, and in those with stage T3 disease (n=9) was (1.30±1.15) mm (t=5.893, P<0.001). A cutoff of d >3 mm yielded specificity and positive predictive value for diagnosing stage T1-T2 disease of both 100%, sensitivity of 95.7% and negative predictive value of 90%. The optimum threshold of d was >3.05 mm, and Youden index was 0.957. Conclusions: High-resolution MRI can show the DF and accurately evaluate the relationship of DF with tumor in rectal cancer patients. Analysis on d value can provide an objective basis for the safe preservation of DF.

Anatomy research on Denonvilliers fascia and its significance in nerve-preservation rectal cancer surgery / 中华胃肠外科杂志

Urinary and sexual dysfunctions due to intraoperative pelvic autonomic nerve injury have become the most common complications of rectal cancer surgery, seriously affecting postoperative quality of life. How to protect the nerve and urogenital function while ensuring radical resection for rectal cancer has become the focus of research. We previously carried out a series of systematic studies on Denonvilliers fascia, an important anatomical structure closely related to protection of pelvic autonomic nerve, and demonstrated the importance of Denonvilliers fascia in preservation of intraoperative pelvic autonomic nerve and protection of postoperative urogenital function from aspects of anatomy, physiology, tissue, operation practice and so on. Meanwhile, based on the interim results of our multicenter randomized controlled study, we confirmed that total mesorectal excision with preservation of Denonvilliers fascia (innovative TME, iTME) could effectively reduce the incidence of postoperative urinary and sexual dysfunctions in male patients with mid-low rectal cancer, without sacrificing oncologic outcome. In this article, combined with our research results, we review the literature on anatomy research progress of Denonvilliers fascia to demonstrate the significance and research prospect of Denonvilliers fascia in the pelvic autonomic nerve preservation surgery for rectal cancer.

Pre-treatment drug resistance of newly reported HIV-1 infected individuals in Wenzhou / 预防医学

Objective@#To know the pre-treatment drug resistance ( PDR ) status of newly reported human immunodeficiency virus type 1 ( HIV-1 ) infected individuals in Wenzhou, so as to provide guidance for antiretroviral therapy ( ART ). @*Methods@# Totally 232 plasma samples of newly reported HIV-1 infected individuals who had not received ART were collected in Wenzhou in 2019. Virus ( HIV-1 ) RNA was extracted, followed by reverse transcription PCR and nested PCR to amplify the pol region and sequence. Resistance mutations and resistance to non-nucleoside reverse transcriptase inhibitors ( NNRTIs ), nucleoside reverse transcriptase inhibitors ( NRTIs ) and protease inhibitors ( PIs ) was analyzed.@*Results@#The pol region sequences from 199 infected patients were obtained and the incidence of PDR was 8.04% ( 16/199 ). Eight genotypes were detected, including circulating recombinant forms ( CRFs ) CRF07_BC ( 47.24%, 94/199 ) and CRF01_AE ( 29.15%, 58/199 ) which were the dominant types. Two unique recombinant forms ( URFs ) were detected, namely URF( CRF01_AE/BC ) and URF( B/C ) . Thirty-one cases ( 15.58% 31/199 ) had drug-resistant mutations. For NNRTIs, NRTIs and PIs, 20 cases ( 64.52% ) , 2 cases ( 6.45% ) and 9 cases ( 29.03% ) with drug resistance mutations were detected, respectively. The resistance mutations to NNRTIs included K101E, K103N/R, V106I, E138K, V179D/E/T, Y181C, G190A and H221Y. Four cases each had two resistance mutations to NNRTIs. The resistance mutations to NRTIs were V75M and M184V. The resistance mutations to PIs were M46I, L33F and Q58E. For the newly released NNRTI drug Doravirine ( DOR ), two cases were found to have mutations of resistance. @*Conclusions@#The incidence of PDR among newly reported HIV-1 patients in Wenzhou is 8.04%, mainly caused by NNRTIs drug-resistant mutation. Resistance to the new drug DOR has emerged. The surveillance of drug resistance should continue to be strengthened.

Pathogenesis of Vitiligo and Its Prevention and Treatment with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Vitiligo is a common pigmentary disorder characterized by localized or generalized depigmentation of the skin， resulting in milky white or light pink patches with smooth surface but no rashes.Modern medicine believes that it is closely related to immune function， oxidative stress， autoimmune destruction of melanocytes， heredity， and neurochemical factors， but the specific pathogenesis is still unclear.Due to the easy diagnosis but hard management and the high recurrence rate， vitiligo has seriously affected the quality of life and mental health of patients.At present， it is mainly treated with glucocorticoids， immunomodulators， vitamin D3 derivatives， and antioxidants in western medicine， and the resulting short-term outcomes are satisfactory.However， a series of side effects may be caused by the long-term use.Traditional Chinese medicine （TCM） has a long history of dealing with vitiligo.Guided by the rich experience accumulated in daily practice， it exerts the preventive and therapeutic effects against vitiligo via multiple components， multiple targets， and multiple pathways， without inducing obvious adverse reactions， which has made it widely concerned by many doctors and scholars.As the research concerning the prevention and treatment of vitiligo with TCM intensifies， more and more single Chinese medicinals， Chinese medicinal monomers， and compound prescriptions have been proved to play a therapeutic role via multiple mechanisms.After reviewing the articles on the alleviation of vitiligo with TCM published in the past five years and retrieved from the literature databases， this paper summarized the efficacy of TCM in regulating immune dysfunction， improving oxidative stress injury， protecting melanocyte function， adjusting mitochondrial structure and function， and controlling the alteration of intestinal micro-flora and abnormal microRNA （miRNA） expression， so as to clarify the pathogenesis of vitiligo and provide theoretical and scientific basis for the in-depth study and clinical application of TCM in the prevention and treatment of vitiligo.

The diagnostic value of flow cytometry in patients with lymphoma associated hemophagocytic syndrome / 中华内科杂志

Objective:To evaluate the reliability of flow cytometry (FCM) for diagnosing lymphoma associated hemophagocytic syndrome (LAHS).Method:The clinical data in 57 patients with hemophagocytic lymphohistiocytosis (HLH)were retrospective analyzed at Peking University Shenzhen Hospital from July 2010 to July 2019. All patients were performed bone marrow FCM and bone marrow pathological examination before final diagnoses were made. The golden diagnosis criterion was based on clinical, biochemical and histopathological evidence, which was regarded as the standard to evaluate the sensitivity and specificity of FCM analysis in diagnosing LAHS.Results:Among 57 cases, 36 cases were eventually diagnosed with LAHS, including 15 B-cell lymphoma(14 diffuse large B-cell lymphoma, 1 B-cell lymphoma with reactive T-cell hyperplasia), 13 aggressive NK/T cell lymphoma/leukemia, 2 cases of gamma-delta T-cell lymphoma, 4 angioimmunoblastic T-cell lymphoma, 1 enteropathy-associated peripheral T-cell lymphoma and 1 anaplastic T-cell lymphoma. Lymphoma cells in bone marrow were detected in all patients by FCM except one ENTCL patient. The sensitivity and the specificity of FCM in LASH compared to bone marrow biopsy were 97.2%( P=0.014)and 90.5%( P=0.488) respectively. In the other 21 non-LAHS patients, T cell receptor Vβ (TCRVβ) rearrangement was detected in 2 patients with Epstein-Barr virus (EBV) associated primary HLH. Conclusions:FCM effectively detects lymphoma cells in bone marrow of lymphoma patients with LHL, suggesting that FCM could be an important indicator for the diagnosis of LAHS. FCM also has the advantage in differentiating LAHS from other HLH.

Formulation Optimization of Hydrophobically-Pullulan Nanoparticles by Box-Behnken Response Surface Methodology / 中国药学杂志

OBJECTIVE: To optimize the preparation of self-assembled doxorubicin-loaded cholesterol-modified pullulan nanoparticles(DOX-CHSP-SAN) by response surface methodology. METHODS: DOX-CHSP-SAN was prepared by dialysis method with the amphiphilic carrier of cholesterol-modified pullulan (CHSP) and the model drug of doxorubicin(DOX). Box-Behnken Design (BBD) response surface method was used to optimize the preparation process of DOX-CHSP-SAN. The morphology, average particle size, Zeta potentia, the encapsulation efficiency, drug loading of doxorubicin and the drug release characteristics in vitro were determined. RESULTS: The optimized DOX-CHSP-SAN has a round spherical shape with an average particle size of (117.1±3.4) nm, PDI of (0.205±0.023), Zeta potential of (-26.1±0.135) mV, the encapsulation efficiency was (68.17±0.93)%, and the drug loading was (6.84±0.47)%. The in vitro release behavior in PBS of pH 7.4 was consistent with the Weibull equation. CONCLUSIO:N The DOX-CHSP-SAN prepared by the dialysis method and optimized by the response surface method is round and smooth, the particle size is small and uniform, the encapsulation efficiency and the drug loading amount are high, and the in vitro release has the sustained release characteristics.

Therapeutic effect of ticagrelor on patients with clopidogrel resistant acute coronary syndrome / 心血管康复医学杂志

Objective : To study therapeutic effect of ticagrelor on patients with clopidogrel resistant acute coronary syndrome (CPGR‐ACS).Methods :A total of 138 patients underwent PCI and suffered CPGR‐ACS after PCI in our hospital were selected .Patients were randomly and equally divided into routine treatment group (received intensive therapy of clopidogrel + aspirin) and ticagrelor group (received ticagrelor + aspirin) ,both groups were treated for 90d .Platelet inhibition rate (PIR) ,serum levels of matrix metalloproteinase (MMP)‐2 andhsCRP ,heart rate vari‐ability (HRV) before and after treatment ,incidence of major adverse cardiovascular events (MACE) and hemor‐rhage were observed and compared between two groups .Results :After treatment ,compared with routine treatment group ,there was significant rise in PIR [ (25. 76 ± 4.63)% vs.(43.97 ± 6.43)%] ,and significant reductions in ser‐um levels of MMP‐2 [(44.85 ± 4. 51) ng／mlvs.(36.96 ± 3.72) ng／ml] and hsCRP [(11.64 ± 1. 2) mg／L vs.(7. 15 ± 0. 72) mg／L] ;significant rise in SDNN [ (62. 87 ± 6.33) msvs.(96.86 ± 9. 72) ms] , SDANN [ (37. 62 ± 3. 81) msvs.(46.38 ± 4.72) ms] , rMSSD [ (25. 70 ± 2.61) ms vs.(38.27 ± 3.93 ) ms] , PNN50 [ (3. 61 ± 0.37)% vs. (4. 93 ± 0. 51)%] and HF [ (163. 27 ± 16. 42 ) ms2 vs.(178. 68 ± 18.21 ) ms2 ] , and significant reduction in LF [ (283. 62 ± 28. 90) ms2 vs.(197.32 ± 20.18) ms2 ] in ticagrelor group , P＝0.001 all.Incidence rate of MACE in ti‐cagrelor group was significantly lower than that of routine treatment group (2. 90% vs.15.94%, P＝0. 009).There was no significant difference in incidence rate of hemorrhage events between two groups , P＝ 0.229. Conclusion :Ticagrelor possesses significant therapeutic effect on patients with clopidogrel resistant acute coronary syndrome , and it＇s safe .

Correlative study of bufogenin constituents in venom of Bufo bufo gargarizans / 中国中药杂志

As known,simultaneous determination of various chemical indicators is one of the future trends in quality control of traditional Chinese medicines because of the extremely complex chemical compositions. This project is to screen the quality markers that can accurately control the quality of the Bufonis Venenum by exploring the intrinsic correlation of components. In this study,venom of Bufo bufo gargarizans from 17 different sources were used as research samples,and the contents of 7 bufogenin were determined by HPLC-DAD. Then,the data obtained were analyzed by Spearman correlation analysis and principal component analysis( PCA). In addition,a stepwise regression analysis was used to establish a predictive model for the contents of the seven bufogenin components( independent variable) and the total contents of the bufogenin( dependent variable). The results indicated that there is a significant positive correlation between the contents of telocinobufagin and cinobufotalin,and there is a significant positive correlation between the contents of bufalin,cinobufagin and resibufogenin. In contrast,the contents of telocinobufagin and cinobufotalin are negatively correlated with the contents of bufalin,cinobufagin and resibufogenin. However,the correlation between gamabufotalin and bufotalin and other components are not obvious. Furthermore,further study found that there is a correlation between the sum of the contents of bufalin,cinobufagin and telocinobufagin and the total contents of the bufogenin. In fact,the application of bufalin,cinobufagin and telocinobufagin as the quality control indicators of the Bufonis Venenum can better reflect the quality characteristics of the Bufonis Venenum compared with the previous quality control indicators. The conclusions will provide a reference for the revision of the quality standards of the Bufonis Venenum.

Mechanism study of the transmission of moxibustion heat in human acupoint tissues / 针灸推拿医学（英文版）

Objective:To discuss the topical action characteristics of the biological transmission of moxibustion heat via temperature collection and numerical modeling.Methods:Temperature of moxibustion was measured at multiple points at a distance of 3 cm to obtain the moxibustion temperature field nephograms by the high-accuracy temperature measure array.Finite element analysis was used to imitate the three-dimensional dynamic distribution of temperature in acupoint tissues.Results:Through numerical analysis,the one-dimensional,two-dimensional and three-dimensional distributions of temperature in human acupoint tissues at 5 min of moxibustion were established.The result showed that moxibustion heat mainly transmitted from the surface of the tissue to the internal,and the influence of moxibustion heat decreased with the depth of the tissue.The analysis of the nephograms of acupoint tissue temperature at 5,10,15 and 20 min of moxibustion showed that with the increase of the moxibustion time,the temperature in acupoint tissues constantly rose,and the transmission depth of moxibustion heat also further expanded inside acupoint.Conclusion:By establishing the three-dimensional dynamic model of heat transmission inside acupoint tissues with the biological parameters of human tissues and the temperature values obtained,this study used finite element analysis software ANSYS 14.0 and discovered the rules in the transmission of heat in body tissues during moxibustion,and the features in moxibustion heat transmission (from the proximal to the distant) and heat penetration (from the surface to the internal).This study provides theoretical and experimental support for the application of moxibustion in clinical practice.

Correlation of polymorphism of rs1260326 loci in glucokinase regulatory protein gene with primary gout and hyperuricemia in Enshi population / 中华风湿病学杂志

Objective To investigate the relationship between rs1260326 polymorphism of glucokinase regulatory protein gene and hyperuricemia and primary gout in Enshi area populations.Methods One hundred and fifty-eight primary gout,190 hyperuricemia and 104 healthy controls (normal group) in total were collected.Hi-single nucleotide polymorphism (SNP) combined with multiplex polymerase chain reaction (PCR) with next generation sequencing techniques were used for gene polymorphism analysis,and the relationship between different alleles or genotypes and susceptibility to primary gout and hyperuricemia were analyzed.The measurement data and numeration data were statistically analyzed with t test and x2 test respectively.Logistic regression analysis was used to assess the relative risk of gout and hyperuricemia.Results The frequency of rs1260326 genotype CC,TC,TT was 8.8％(14/158),60.8％(96/158),30.4％(48/158) respectively in gout patients,15.8％ (30/190),54.7％ (104/190),29.5％ (56/190) in hyperuricemia patients,21.2％ (22/104),45.1％ (47/104),33.7％(35/104) in the normal group,the genotype distribution was significantly different in gout group and normal group (x2=9.895,P=0.007),and there was no difference between hyperuricemia group and normal group (x2=2.665,P=0.264).Allele C and T frequency was 39.2％(124/316) and 60.8％(192/316) in gout patients,43.2％(164/380) and 56.8％(216/380) in hyperuricemia patients,43.8％(91/208) and 56.2％(117/208) in the normal group.Allele T was the susceptible gene for gout.Logistic regression analysis showed that genotypes TC,TT,TC+TT increased the risk of gout.And Logistic regression analysis showed that rs1260326 single nucleotide polymorphism and hyperuricemia were no susceptibile.Conclusion Glucokinase regulatory protein (GCKR) rs1260326 sin-gle nucleotide polymorphism may be associated with primary gout risk in En Shi area,but has no significant correlation with hyperuricemia.