[Efficacy of alternate mucosa-submucosa clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection].

Objective: To analyze the efficacy of alternate titanium clip closure in preventing postoperative complications for patients with gastric mucosal lesions after endoscopic submucosal dissection (ESD). Methods: Clinical data of patients with gastric mucosal lesions who underwent ESD in the Department of Gastroenterology, Zhongda Hospital, Southeast University, were retrospectively collected from January 1, 2013 to August 31, 2023. According to the postoperative wound closure status, the patients were divided into completely closed group (complete closure of ESD wounds using alternate titanium clip closure), partially closed group (partial closure of ESD wounds), and unclosed group (without use of clips for treatment of ESD wounds). The incidence of postoperative complications as well as wound healing at 1 month and 3 months after surgery were compared among three groups, and the factors related to delayed bleeding after ESD for gastric mucosal lesions were analyzed through multiple logistic regression analysis. Results: A total of 846 patients were included, 430 cases in the completely closed group, including 300 males and 130 females, age [M (Q1, Q3)] was 65(56, 72) years old; one hundred and nine cases in unclosed group, including 78 males and 31 females, aged 66 (60, 71) years; and 307 cases in the partially closed group, including 214 males and 93 females, aged 66 (59, 71) years. The difference in the rate of delayed postoperative bleeding between the completely closed group [2.1% (9/430)] and the unclosed group [5.5% (6/109)] was not statistically significant (P=0.072), but both were lower than that of the partially closed group [9.4% (29/307), P<0.05)]. Further stratified analysis showed that, for the lesions located in the lower 1/3 of the stomach, the rate of postoperative bleeding was lower in the completely closed group than in the partially closed and unclosed groups [0.9% (2/222) vs 11.4% (4/35) vs 9.5% (7/74), respectively, P<0.001]. For lesions≥50 mm in length, the rate of postoperative bleeding was lower in the completely closed group than that in the partially closed and unclosed group[0 vs 11.8% (2/17) vs 20.5% (15/73), respectively, P=0.004]. The incidence of postoperative abdominal pain in the completely closed group [84.2% (363/430)] was lower than that in the unclosed group [97.2% (106/109)] and the partially closed group [95.4% (293/307), both P<0.001)]. The score of postoperative abdominal pain in the completely closed group [0 (0, 1)], was lower than that in the unclosed group [3 (2, 3)], and that in the partially closed group [2 (1, 3)] (both P<0.001). The wound healing rate of the completely closed group [80% (176/220)] was higher than that of the unclosed group [52.3% (33/63)] and the partially closed group [52.2% (83/159)] at 1 month postoperatively (both P<0.001); the healing rate of all three groups reached 100% at 3 months postoperatively. Multiple logistic regression analysis showed that the presence of ulcers or scars on the surface of the lesion (OR=2.930, 95%CI:1.503-5.712, P=0.002), and the diameter (OR=1.031, 95%CI:1.015-1.047,P<0.001) were related factors for postoperative bleeding. Conclusions: The alternate titanium clip closure surgery can reduce postoperative abdominal pain and shorten wound healing time in patients with gastric mucosal lesions after ESD surgery. The risk of postoperative bleeding can be reduced for lesions with a diameter≥50 mm and located in the lower 1/3 of the stomach.

[Therapeutic strategies, practice, and prospect of a clinical cure for chronic hepatitis B in China].

Clinical cure (herein referred to as functional cure) is currently recognized as the ideal therapeutic goal by the guidelines for the prevention and treatment of chronic hepatitis B (CHB) at home and abroad. China has achieved significant results in research and exploration based on pegylated interferon alpha therapeutic strategies to promote the effectiveness of CHB clinical cure rates in clinical practice. The summary and optimization of clinical cure strategies in different clinical type classifications, as well as the exploration of clinical cure continuity and long-term outcomes, are of great significance for solving the current bottleneck problem and our future efforts in the developmental directions of clinical cure in CHB populations.

[The timing and challenges of early intervention for infantile esotropia].

Infantile esotropia is a common ophthalmic disease in children. A lot of clinical and basic research evidence suggests that early surgery enhances sensory and ocular motor development. However, the proper timing of surgery has been debated for decades. In addition, there is more likely instability of deviation in the preoperative evaluation of infants, and even if the patient achieved alignment after surgery, the defects in binocular vision may accompany for a lifetime. This article analyzes the difficulties and key points of early intervention for infantile esotropia, aiming to provide scientific ideas for the early treatment of children with infantile esotropia in China.

Opioid-free anesthesia with lidocaine for improved postoperative recovery in hysteroscopy: a randomized controlled trial.

BACKGROUND: Anesthesia with opioids negatively affects patients' quality of recovery. Opioid-free anesthesia attempts to avoid these effects. This study aimed to evaluate the effect of opioid-free anesthesia on the quality of recovery, using lidocaine on patients undergoing hysteroscopy. METHODS: A parallel-group, randomized, double-blind, controlled trial was conducted in Yichang Central Peoples' Hospital, Hubei Province, China, from January to April, 2022. We included 90 female patients (age: 18-65 years, American Society of Anesthesiologists Physical Status Class I-II) scheduled for elective hysteroscopy, 45 of whom received lidocaine (Group L), and 45 received sufentanil (Group S). Patients were randomly allocated to receive either lidocaine or sufentanil perioperatively. The primary outcome was the quality of postoperative recovery, which was assessed using the QoR-40 questionnaire (a patient-reported outcome questionnaire measuring the quality of recovery after surgery). RESULTS: The two groups were similar in age, American Society of Anesthesiology physical status, height, weight, body mass index, and surgical duration. The QoR scores were significantly higher in Group L than Group S. The incidence of postoperative nausea and vomiting, as well as the time to extubation were significantly lower in Group L than Group S. CONCLUSION: Opioid-free anesthesia with lidocaine achieves a better quality of recovery, faster recovery, and a shorter time to extubation than general anesthesia with sufentanil. TRIAL REGISTRATION: The trial was registered on January 15, 2022 in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showprojen.aspx?proj=149386 ), registration number ChiCTR2200055623.(15/01/2022).

[Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension].

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.

[Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase â ¢ clinical trial].

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

[Efficacy and safety of adalimumab in patients with Crohn's disease].

Objective: To assess the effectiveness and safety of adalimumab in Crohn's disease (CD) patients. Methods: We retrospectively reviewed the charts of 41 CD patients who received adalimumab in Zhongda Hospital Southeast University from January 2020 to August 2021. General clinical data, laboratory results, endoscopy and radiologic findings were collected, meanwhile, disease activity and safety events were evaluated at baseline and at 12, 24 and 48 weeks of administration. Adalimumab was given subcutaneously once every 2 weeks in doses of 160 mg for the first time, 80 mg for the second time, and 40 mg for each subsequent time. Results: The clinical remission rates at 12, 24, and 48 weeks of treatment were 43.9% (18/41), 60.6% (20/33), 60.9% (14/23), and the clinical response rates were 75.6% (31/41), 69.7% (23/33), and 56.5%( 13/23), respectively. The proportion of endoscopic remission at 12, 24 and 48 weeks were 4/14, 2/6, 1/4 in patients undergoing endoscopy, and 1/14 patients achieved mucosal healing at 24 weeks. Primary nonresponse rate (PNR) was 17.1% (7/41), loss of response (LOR) rate was 14.6% (6/41). The incidence of adverse reactions was 9.8%(4/41). Conclusion: Adalimumab can effectively relieve the clinical symptoms and intestinal disease activities of Crohn's disease, and deserves to be popularized clinically. Patients with disease course <2 years, first-line biologics, low baseline HBI score, and longer duration of medication may have better results.

[Comparison of the outcomes between open and hybrid approaches in the treatment of thoracoabdominal aortic aneurysms repair].

OBJECTIVE: Thoracoabdominal aortic aneurysm is one of the most challenging aortic diseases. Open surgical repair remains constrained with considerable perioperative morbidity and mortality. The emergence of a hybrid approach utilizing visceral debranching with endovascular aneurysm repair has brought an alternative for high-risk patients. This study aimed to compare the short- and long-term outcomes between hybrid and open repairs in the treatment of thoracoabdominal aortic aneurysms. METHODS: In this retrospectively observational study, patients with thoracoabdominal aortic aneurysm treated in a single center between January 2008 and December 2019 were reviewed, of whom 11 patients with hybrid repair, and 18 patients with open repair were identified. Demographic characteristic, operative data, perioperative morbidity and mortality, freedom from reintervention, and long-term survival were compared between the two groups. RESULTS: In the hybrid repair group, the patients with dissection aneurysm, preoperative combined renal insufficiency, and American Society of Anesthesiologists (ASA) score of 3 or more were significantly overwhelming than in the open repair group. The operation time of debranching hybrid repair was (445±85) min, and the intraoperative blood loss was (955±599) mL. There were 2 cases of complications in the early 30 days after surgery, without paraplegia, and 1 case died. The 30-day complication rate was 18.2%, and the 30-day mortality was 9.1%. The operation time of the patients with open repair was (560±245) min, and the intraoperative blood loss was (6 100±4 536) mL. Twelve patients had complications in the early 30 days after surgery, including 1 paraplegia and 4 deaths within 30 days. The 30-day complication rate was 66.7%, and the 30-day mortality was 22.2%. The bleeding volume in hybrid repair was significantly reduced compared with open repair (P < 0.001). Besides, the incidence of 30-day complications in hybrid surgery was significantly reduced (P=0.011). During the follow-up period, there were 4 reinterventions and 3 deaths in hybrid repair group. The 1-year, 5-year, and 10-year all-cause survival rates were 72%, 54%, and 29%, respectively. In open repair group, reintervention was performed in 1 case and 5 cases died, and the 1-year, 5-year, and 10-year all-cause survival rates were 81%, 71%, and 35%, respectively. There was no significant difference between hybrid repair and open repair in all-cause survival and aneurysm-specific survival. CONCLUSION: Hybrid approach utilizing visceral debranching with endovascular aneurysm repair is a safe and effective surgical method for high-risk patients with thoracoabdominal aortic aneurysms. The incidence of early postoperative complications and mortality is significantly reduced compared with traditional surgery, but the efficacy in the medium and long term still needs to be improved.

[Clinical and histopathological features of immune checkpoint inhibitor-related myositis in patients with advanced non-small cell lung cancer].

Objective: To investigate the clinicopathologic features and outcome of myositis in patients with advanced non-small cell lung cancer treated with immune checkpoint inhibitors. Methods: The patients diagnosed with immune checkpoint inhibitor-related (ICI) myositis in the database of Respiratory Pathology Center of The First Affiliated Hospital, Guangzhou Medical University from June 2019 to December 2020 were retrospectively analyzed. We reported the muscle histology and main clinical manifestations of the patients in this study. Seven patients with advanced non-small cell lung cancer and ICI related myositis were examined; all of the patients were male, with a median age of 64 (range 42-79) years. Results: All seven patients developed myositis under therapy (three for pembrolizumab, three for sintilimab, and one for camrelizumab). Median delay between ICI initiation and myositis onset was 45 (range 15-176) days. Clinical manifestations were dominated by acute or subacute myalgia and limb weakness. Four patients had evidence of myocarditis. In all of the 7 patients, creatine kinase levels were elevated (median 2 354.4, range 468.6-19 709.2 U/L), while myositis-associated antibodies Ro-52 were positive in four patients. Muscle biopsy showed evident multifocal necrotic myofibers and infiltration of inflammation in two patients. Other patients only showed non-specific endomysial inflammation. Infiltration of inflammation mainly consisted of CD8+ T cells and CD68+ histocytes. After the identification of ICI related myositis, ICI treatment was withdrawn in all patients; 6 patients received corticosteroids therapy. All patients had shown marked clinical improvement. Conclusions: ICI myositis presents with remarkably homogeneous and unique clinicopathologic features, and half of the patients exhibit heightened risk for adverse cardiovascular events, which can be life-threatening if not treated in time. Timely identification of these patients, ICI withdrawal and rapid initiation of corticosteroids therapy can significantly improve patient outcome and/or save patients' lives.

[Endovascular abdominal aortic aneurysm repair with a new stent graft:early results from a multicenter study].

Objective: To examine the safety and effectiveness of a new stent graft system for endovascular repair of abdominal aortic aneurysm(AAA). Methods: This is a prospective,multi-center,single-arm clinical trial. The patients with AAA treated with a new stent graft system were enrolled at 21 centers from September 2018 to September 2019 in China. Follow-up was performed before discharge, and at 30, 180, 360 days after operation, respectively. The primary safety endpoint was the incidence of major adverse events(MAE) within 30 days. The primary efficacy endpoint was the success rate of AAA treatment at 360 days. Secondary safety endpoints were the incidence of perioperative access complications and acute lower limb ischemia,all-cause mortality, AAA related mortality and incidence of serious adverse events (SAE) at 180 and 360 days. Secondary efficacy endpoints were the incidence of type Ⅰ or Ⅲ endoleak,stent displacement,and conversion to open surgery or re-intervention at 180 and 360 days. Results: One hundred and fifty-six patients were enrolled,including 137 males and 19 females. The age was (68.9±6.9) years (range:48.2 to 84.6 years).Maximum aneurysm diameter was (50.8±11.2) mm (range:25.0 to 85.0 mm),diameter of proximal landing zone was (21.2±2.5) mm (range:17.0 to 29.5 mm),and length of proximal landing zone was (31.4±13.0) mm (range:11.0 to 75.0 mm).The incidence of MAE was 1.3% (2/156) at 30 days,both were all-cause death cases. The success rate of AAA treatment was 88.5% (138/156) at 360 days. No perioperative access complication and acute lower limb ischemia occurred. All-cause mortality was 2.0% (3/154) at 180 days and 2.6% (4/153) at 360 days,and there was no AAA related death. The incidence of SAE was 23.0%(35/152) at 180 days and 30.5%(46/151) at 360 days, and no device-related SAE occurred. The incidence of type Ⅰor Ⅲ endoleak was 3.4% (5/147) at 180 days and 3.5% (5/144) at 360 days. Conclusion: The new stent graft system is easy to operate,and early-term safety and effectiveness results are expected.

[The role of Botulinum toxin type A in the treatment of childhood strabismus].

Botulinum toxin type A (BTX-A) can change the eye alignment system through chemodenervation on extraocular muscles. The breakdown in the balance of eye alignment system which is supported by agonistic and antagonistic muscles, in combination with brain feedback, can stimulates muscle remodeling to reconstruct new binocular vision and restore eye alignment. Since BTX-A was approved by FDA in 1989 for the treatment of strabismus, it has become one of the important non-surgical treatments for strabismus in children. It has the advantages of low invasiveness, short duration of anesthesia and scar-free after treatment. This review will introduce the history, injection methods, and types of BTX-A, as well as its application in the treatment of various types of strabismus in children.

Gender-specific SBNO2 and VPS13B as a potential driver of osteoporosis development in male ankylosing spondylitis.

To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients. INTRODUCTION: Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS. METHODS: Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the limma package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes. RESULTS: A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected. CONCLUSIONS: Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.

[Blue light regulates the expression of brain derived neurotrophic factor in the habenula nucleus of depression-like rats induced by light deprivation].

Objective: To investigate the regulatory effect of blue light on the expression of brain derived neurotrophic factor (BDNF) in the habenula nucleus of depression-like rats induced by light deprivation. Methods: male SD rats were exposed to white light (white light control group, 20 rats) and constant darkness (depression model group, 60 rats), respectively. 18 days later rats in depression model group were randomly divided into three groups: depression model group (treated with constant darkness), blue light group (treated with blue light) and red light group (treated with red light). Rats in white light control group were kept in white light. All rats exposed to light were in a standard 12∶12 h Light/Dark condition at 20 lx for 36 days. Sucrose preference test was applied to evaluate depression-like symptoms of rats. The c-fos+cells in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus were detected. The phosphoylation of cAMP-response element binding protein (CREB) and the relative BDNF protein level in the habenula nucleus were measured. Results: Sucrose intake per kg body weight increased in rats exposed to blue light and returned to the level of control group (P>0.05). Sucrose intake per kg body weight in red light group and depression model group were lower than control group (P<0.05). More c-fos+cells were detected in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus from blue light group than those from depression model group (P<0.05). The relative BDNF protein level and the phosphoylation of CREB in the habenula nucleus from blue light group were higher than those from depression model group (P<0.05). Conclusion: Blue light could relieve depression-like symptoms in light-deprived rats. Exposure to blue light could activate neurons in the habenula nucleus to which intrinsically photosensitive retinal ganglion cells projected. Blue-light-mediated antidepressant effect might involve in the activation of CREB/BDNF signal transduction pathways in the habenula nucleus.

[Grading model for drug-coated balloon treating femoropopliteal de novo lesions and potential benefit from debulking].

Objectives: To establish a grading model on prognosis of drug-coated balloon (DCB) treatment on femoropopliteal de novo lesions, and assess whether patients at high risk could benefit from combination of directional atherectomy(DA). Methods: The clinical data of 114 patients with femoropopliteal de novo lesions admitted to Department of Vascular Surgery, Peking University People's Hospital from October 2015 to January 2019 were collected retrospectively. There were 95 patients(108 limbs) underwent DCB treatment, including 66 males and 29 females, aged 71.9 years old(range:48 to 91 years), and 19 patients (21 limbs) underwent DA combined with DCB treatment, including 13 males and 6 females, aged 69.5 years old(range: 62 to 80 years). The demographic data, intraoperative and postoperative conditions of the patients were collected. Cox regression model was performed for modeling and then goodness of fit was tested. Kaplan-Meier estimate was carried out between the two groups for patients at high risk and low risk, respectively. Results: All patients were followed up for more than 24 months. Restenosis occurred on 34 limbs in DCB group and 3 limbs in DA+DCB group. Severe calcification(HR=3.804, 95%CI:2.460 to 5.883), popliteal artery involvement (HR=2.104, 95%CI:1.368 to 3.236), long lesion (HR=1.824, 95%CI:1.196 to 2.780), poor runoff(HR=1.736, 95%CI:1.025 to 2.940), chronic kidney disease(HR=1.601, 95%CI:1.040 to 2.463) were independent risk factors of restenosis after DCB treatment, and were defined 3, 2, 1, 1 and 1 points, respectively. Total points≥3 was regarded as high risk group. Kaplan-Meier analysis showed that patients in low risk group did not benefit from DA+DCB comparing with DCB with regard to primary patency at 24 months (77.78% vs. 90.31%, P=0.271) while patients benefited from DA+DCB comparing with DCB in high risk group(88.26% vs. 20.80%, P<0.01). Conclusions: The grading model shows satisfying clinical value. The clinical effect of DA+DCB is better than DCB along in high risk group. Patients at high risk are supposed to receive aggressive vessel preparation like DA.

[Transbronchial lung cryobiopsy in diffuse lung disease: a pathological analysis of 173 cases].

Objective: To evaluate the value of transbronchial lung cryobiopsy (TBCB) in pathological diagnosis for diffuse lung disease. Methods: The clinicopathological data of 173 patients from the first affiliated hospital of Guangzhou medical university between Jaunary 2017 and June 2019 with transbronchial lung cryobiopsy of diffuse lung disease were retrospectively analyzed and summarized with review. Among 173 cases, TBCB and conventional transbronchial lung biopsy (TBLB) were performed in 54 patients. The size of biopsy samples and diagnostic yield were compared. Results: Among 173 cases, the diagnostic yield was 85.54% (148/173) , 160 (92.49%) cases provided definite diagnosis and valuable pathological results, according to age, sex, occupation, past history, contact history, smoking history, laboratory serology and imaging findings. Among 160 cases, there were 72 cases of known etiology (45.00%), 27 cases of idiopathic interstitial pneumonia (16.88%), 7 cases of granulomatous lesions (4.38%) and 54 cases of other types (33.75%). With TBCB and TBLB in 54 patients, the specimens sizes of TBCB and TBLB were (3.3±1.3) mm(2) and (1.0±0.3) mm(2) respectively (t'=12.67 P<0.01) . The diagnostic yields of TBCB and TBLB were 81.48% (44/54) and 42.59% (23/54) respectively (χ(2)=17.33, P<0.01) . The diagnostic yields of TBCB and TBLB for interstitial lung diseases were 48.15% (26/54) and 5.56% (3/54) respectively (χ(2)=24.94, P<0.01) . However, the diagnostic yields of TBCB and TBLB for the other diffuse lung disease except interstitial lung diseases were 33.33% (18/54) and 37.04% (20/54) respectively, with no significant difference (χ(2)=0.1624, P=0.687). Conclusion: Compared with TBLB, TBCB has obvious advantages and application value in the diagnosis of diffuse pulmonary diseases, especially interstitial pulmonary diseases.

[Spinal cord stimulation for non-reconstructable chronic ritical limb ischemiae: a case report].

Peripheral arterial disease is one part of systematic atherosclerosis, becoming a heavy burden of human health. Patients in end stage of peripheral arterial disease manifest critical limb ischemia with severe rest pain and refractory ulcer. Surgical revascularization is the optimal option for patients with critical limb ischemia to avoid major amputation and improve quality of life. However, some of them contraindicate surgical revascularizations owing to coexisting morbidities. Spinal cord stimulation is reported to be effective and minimally invasive in pain relief and limb salvage for patients with limb ischemia. Here, we reported one case with chronic critical limb ischemia and gangrene of foot who underwent spinal cord stimulation, which was, as we knew, the first case in China. He was diagnosed with Burger disease and accompanied with history of stroke, chronic obstructive pulmonary disease and Castleman's disease. It showed totally occlusive lesions of external iliac and femoropopliteal artery and no outflows below the knee in the computed tomography angiography. Given the complexity of lesions and weakness of the patient, spinal cord stimulation was indicated for control of rest pain and limb salvage. As specified, we implanted the temporary neurostimulator as the first step. After 2 weeks from temporary neurostimulator implantation, the patient achieved significant relief in intensity of pain, and acquired 20% improvement of transcutaneous oxygen pressure. The satisfactory results indicated probable effectiveness of spinal cord stimulation, thus we performed the permanent neurostimulator implantation 1 month later. During 2 months of follow-up, the patients stabilized at Fountain III with pain relief with one kind of nonsteroidal anti-inflammatory drug. In our case, we confirmed the significant validity of spinal cord stimulation for pain control and consequent improvement of quality of life in non-reconstructable chronic critical limb ischemia. Furthermore, we reviewed that a number of published studies suggested that spinal cord stimulation be a reasonable option for patients with critical rest pain, especially who contraindicated surgical revascularization. The application of spinal cord stimulation in pain relief for non-reconstructable chronic critical limb ischemia was approved by related guidelines released by European Society of Cardiology and Trans-Atlantic Inter-Society Consensus. Further investigations are required for assessing the long-term outcome in limb salvage.

[Efficacy of sequential therapy with telbivudine in treatment of HBeAg-positive chronic hepatitis B patients with partial response to pegylated interferon-α therapy].

Objective: To investigate the efficacy of sequential therapy with telbivudine in the treatment of HBeAg-positive chronic hepatitis B (CHB) patients with partial response after a standard course of interferon therapy. Methods: A retrospective cohort study was performed for 58 HBeAg-positive CHB patients with partial response at the end of interferon therapy (48-60 weeks) from January 2009 to December 2013. According to whether telbivudine was used sequentially or withdrawn at the end of the course of treatment, the patients were divided into telbivudine sequential therapy group and withdrawal group, and the two groups were compared with in terms of biochemical, virological, and serological response rates. The chi-square test, the t-test, and the non-parametric test were used based on data type. Results: A total of 58 patients were enrolled in this study, with 31 in the telbivudine sequential therapy group and 27 in the withdrawal group. At 12 and 24 weeks after interferon therapy ended, the telbivudine sequential therapy group had a significantly higher HBeAg clearance rate than the withdrawal group (22.6%/29.0% vs 0%/3.7%, P < 0.05). At week 48 of follow-up, the telbivudine sequential therapy group had a significantly higher combined response rate than the withdrawal group (22.6% vs 0%, P = 0.015). Among the 31 patients in the telbivudine sequential therapy group, 11 had an increase in creatine kinase during the administration of telbivudine. No patient in either group experienced serious adverse reactions during follow-up, such as muscular soreness, myositis, peripheral neuropathy, renal dysfunction, and liver function decompensation. Conclusion: In HBeAg-positive CHB patients with partial response to interferon therapy, sequential therapy with telbivudine can increase serological HBeAg clearance rate and combined response rate at week 48, and it is safe in HBeAg-positive CHB patients achieving partial response at the end of interferon therapy.

[HBsAg loss with Pegylated-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)-ide analog: new switch study].

Objective: Hepatitis B surface antigen (HBsAg) loss is seldom achieved with nucleos(t)ide analog (NA) therapy in chronic hepatitis B patients but may be enhanced by switching to finite pegylated-interferon (Peg-IFN) alfa-2a. We assessed HBsAg loss with 48- and 96-week Peg-IFN alfa-2a in chronic hepatitis B patients with partial response to a previous NA. Methods: Hepatitis B e antigen (HBeAg)-positive patients who achieved HBeAg loss and hepatitis B virus DNA < 200 IU/mL with previous adefovir, lamivudine or entecavir treatment were randomized 1:1 to receive Peg-IFN alfa-2a for 48 (n = 153) or 96 weeks (n = 150). The primary endpoint of this study was HBsAg loss at end of treatment. The ClinicalTrials.gov identifier is NCT01464281. Results: At the end of 48 and 96 weeks' treatment, 14.4% (22/153) and 20.7% (31/150) of patients, respectively, who switched from NA to Peg-IFN alfa-2a cleared HBsAg. Rates were similar irrespective of prior NA or baseline HBeAg seroconversion. Among those who cleared HBsAg by the end of 48 and 96 weeks' treatment, 77.8% (14/18) and 71.4% (20/28), respectively, sustained HBsAg loss for a further 48 weeks. Baseline HBsAg < 1 500 IU/mL and week 24 HBsAg < 200 IU/mL were associated with the highest rates of HBsAg loss at the end of both 48- and 96-week treatment (51.4% and 58.7%, respectively). Importantly, extending treatment from 48 to 96 weeks enabled 48.3% (14/29) more patients to achieve HBsAg loss. Conclusion: Patients on long-term NA who are unlikely to meet therapeutic goals can achieve high rates of HBsAg loss by switching to Peg-IFN alfa-2a. HBsAg loss rates may be improved for some patients by extending treatment from 48 to 96 weeks, although the differences in our study cohort were not statistically significant. Baseline and on-treatment HBsAg may predict HBsAg loss with Peg-IFN alfa-2a.

A 15-year-long Southern blotting analysis of FMR1 to detect female carriers and for prenatal diagnosis of fragile X syndrome in Taiwan.

Here, we review the results of Southern blotting analyses of the FMR1 gene performed in our reference laboratory in Taiwan over a 15-year period. In total, 725 high-risk women with a family history of fragile X syndrome (FXS) or idiopathic intellectual disability, 3911 low-risk pregnant women without such family history, and prenatal diagnosis data for 32 foetuses from 24 carrier mothers were included. Only 2 carriers were in the low-risk group, which indicated a prevalence of 1 of 1955 women (95% confidence interval: 1/7156-1/539). A total of 100 carriers were found to be in the high-risk group, thus revealing a significantly higher frequency than the low-risk group (100/725 vs 2/3911, P<0.0001). Eight of the 14 foetuses that inherited the maternal mutant allele were verified to have a full mutation, with the smallest maternal pre-mutation allele carrying 56 CGG repeats. The overall findings confirmed that the carrier prevalence among low-risk women in Taiwan is significantly lower than that reported in western countries. Therefore, the most important step for preventing FXS in Taiwan would be to focus on high-risk women by promoting general awareness of this disease and spreading knowledge regarding the benefits of carrier screening and prenatal testing.

[Impact of CYP2C19 genotype and platelet function on clinical outcome in coronary atherosclerotic heart diseases patients received clopidogrel post percutaneous coronary intervention].

Objective: To analyze association of CYP2C19 genotype and platelet function phenotype and their impact on clinical outcomes including bleeding events of coronary artery disease(CAD) patients received clopidogrel post percutaneous coronary intervention(PCI). Methods: Coronary atherosclerotic heart diseases patients underwent elective PCI and coronary stent implantation in Fuwai hospital were prospectively enrolled during May 2012 to April 2013. Patients were assigned into groups by genotype of CYP2C19 (extensive metabolizers, intermediate metabolizers, and poor metabolizers) and phenotype of platelet function (clopidogrel responders, semi-responders, and non-responders). The rates of major adverse cardiovascular events, combined cardiovascular events, and bleeding events were recorded during a at least 12 months follow-up period and compared among above defined groups. The association between genotype or phenotype and clinical outcome was assessed using multivariable Cox regression hazards model. Results: Three hundred and eighty patients received coronary stent implantation and met the inclusion criteria of the study, including 157(41.3%) clopidogrel extensive metabolizers, 176(46.3%) intermediate metabolizers, and 47(12.4%) poor metabolizers according to the genotype grouping; 98(25.8%) were responders to clopidogrel, 149(39.2%) were semi-responders, and 133 (35.0%) were non-responders according to the phenotype grouping. Three hundred and seventy-six patients accomplished follow-up. The highest combined cardiovascular events rate was observed in the poor metabolizers (34.0%(16/47)) as compared to the intermediate metabolizers (19.0%(33/174), P=0.026) and the extensive metabolizers (15.5%(24/155), P=0.005). The highest bleeding events rate was observed in the clopidogrel responders (33.7%(33/98)) as compared to the semi-responders (18.9%(28/149), P=0.008) and non-responders (17.7%(23/130), P=0.008). In multivariable Cox regression analysis, the adjusted risk of cardiovascular death, acute myocardial infarction, stent embolism, target lesion revascularization and angina onset was 2.305 times higher in clopidogrel poor metabolizers than in extensive and semi-metabolizers (95%CI=1.208-4.399, P=0.011). The adjusted HR for bleeding events was 0.540 (95%CI=0.321-0.909, P=0.021) among semi-responders vs. responders, was 0.52 (95%CI=0.301-0.905, P=0.021) among non-responders vs. responders during the 12 months follow-up period. Conclusions: Among CAD patients underwent stenting and clopidogrel treatment, poor CYP2C19 metabolizers group carries a significantly higher risk for combined cardiovascular events than in extensive metabolizers group, while clopidogrel responders patients are at significantly higher risk for bleeding as compared to the semi-responders and non-responders.