[Investigation on the treatment of empagliflozin in glycogen storage disease type Ib].

Objective: To investigate the safety, efficacy and effective dose of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Method: This was a cross sectional study. A total of 28 children with GSDⅠb who started oral empagliflozin treatment from January 2021 to June 2023 in the WeChat group of patients with glycogen storage disease were selected as the study objects. Clinical data such as general situation, current situation of medication and adverse reactions of the children were collected through questionnaires from June 18 to 30, 2023. The differences of symptoms and laboratory tests before and after empagliflozin treatment were compared by using paired chi-square test and Wilcoxon signed rank sum test. Results: Totally 28 children with GSD Ⅰb were from 12 different provinces, autonomous regions and municipalities in China. There were 14 males and 14 females, Empagliflozin treatment was started at the age of 4.8(2.4, 10.8) years, the time of treatment was 14.5(11.3, 21.5) months, the initial dosage was (0.23±0.11) mg/(kg·d), and the maintenance dosage was (0.28±0.12) mg/(kg·d). Empagliflozin showed positive effects on neutropenia, severity of inflammatory bowel disease like symptoms(Z=-3.70, -2.65, both P<0.05), The proportion of recurrent oral ulcers, recurrent bacterial infections and anemia was significantly lower than that before medication 18% (5/28) vs. (46% (13/28), 14% (4/28) vs. 46% (13/28), 21% (6/28) vs. 46% (13/28), χ²=4.05, 5.26, 3.05, all P<0.05). GCSF was once used in 5 children with GSD Ⅰb, all of them had completely stopped GCSF after empagliflozin treatment. The most common adverse events during empagliflozin treatment were hypoglycemia (5 children) and urinary infection (3 children). All 28 patients had no serious adverse reactions. Conclusions: Empagliflozin can increase the neutrophil count of children with GSD Ⅰb, and had a favorable effect on symptoms such as recurrent oral ulcers, and recurrent infection. The common adverse events during empagliflozin treatment were hypoglycemia and urinary infection.

[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).

[Short-term efficacy of empagliflozin in children with glycogen storage disease type â b].

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×109, 0.50×109, 0.48×109, 0.48×109/L to 1.48×109, 3.04×109, 1.10×109, 0.73×109/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.

[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.

[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.

[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.

[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.

[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.

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.

[Surveillance of malaria vectors in Anhui Province from 2016 to 2018].

OBJECTIVE: To understand the population distribution, density, seasonal fluctuation and nocturnal activity of malaria vectors in Anhui Province from 2016 to 2018, so as to provide a data support for formulating the control strategy for imported malaria during the malaria post-elimination stage. METHODS: The malaria vectors were monitored in 105 counties (cities or districts) of Anhui Province from 2016 to 2018, and the population density, seasonal fluctuation and nocturnal activity of the mosquitoes were observed using the lamp trapping and human bait trapping methods. The density of Anopheles mosquitoes was compared among different years, regions and mosquito-capturing sites. RESULTS: Anopheles mosquitoes were captured in 103 counties (cities or districts) of Anhui Province during the period from 2016 to 2018, and a total of 32 494 mosquitoes were captured using the lamp trapping method and 36 228 captured using the human bait trapping method. All captured mosquitoes were morphologically identified as Anopheles sinensis, and no An. anthropophagus was found. The density of An. sinensis peaked from June to August, and the peak nocturnal activity was found during the period between 19∶00 and 23∶00. Among all mosquito-capturing sites, the highest mosquito density was seen in the livestock and poultry sheds (H = 18.835, P < 0.05). The density of An. sinensis varied significantly in regions in 2016 and 2017 (H = 16.655 and 11.566, P < 0.01), and a low density was found in north of the Huai River. CONCLUSIONS: An. sinensis is widely distributed in Anhui Province, which is the currently predominant malaria vector in the province. During the malaria post-elimination stage, the malaria vector monitoring should be intensified and vector control interventions should be timely adopted in epidemic foci of Anhui Province to prevent the local re-transmission of overseas imported malaria.

[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.

[A report of clinical characteristics of 2 Chinese pedigrees with haploinsufficiency of A20 and literature review].

Objective: To summarize the clinical characteristics of patients with haploinsufficiency of A20 (HA20). Methods: The clinical manifestations, laboratory examinations, treatment, outcome and genetic analysis of 4 cases with HA20 hospitalized in Peking Union Medical College Hospital were analysed.Further literature review was done after searching articles in PubMed and Wangfang databases with the key words "HA20" "A20 haploinsufficiency" "TNFAIP3" up to the date of September 2019. Results: The 4 patients were a father and a daughter, as well as a mother and a daughter. Their phenotypes were quite variable, but all of them have been suffering from recurrent oral ulcer since childhood. Elevation of C-reactive protein (13-33 mg/L) and erythrocyte sedimentation rate (21-60 mm/1h) were found in these 4 patients, and there was positive antinuclear antibody in proband 1.The father in pedigree 1 and the 2 patients in pedigrees 2 have been diagnosed with Behçet disease and the proband 1 with undifferentiated connective tissue disease. The 2 patients in pedigree 1 have developed Hashimoto's thyroiditis. After gene sequencing analysis, it was found that all the 4 patients have heterozygous nonsense mutations in TNFAIP3 gene, that is, c.811C>T, p.R271X in pedigree 1 and c.133C>T, p.R45X in pedigree 2.The diagnosis of HA20 was eventually established when sequencing results and their clinical manifestations were both compatible with this disease.A total of 21 articles were retrieved, all in English, with a total of 91 cases from 39 families (including the 4 cases reported in this paper). HA20 was reported more often in female (57, 64.8%). Most patients develop symptoms from childhood, but as many as 53.4% (47 cases) are not correctly diagnosed until adulthood. Oral ulcers, genital ulcers, periodic fever, gastrointestinal symptoms, rashes, and arthritis are the primary manifestations.Hashimoto's thyroiditis is the most common autoimmune diseases that HA20 patients coexist with. Laboratory tests were characterized by significantly elevated inflammatory markers and low to moderate titers of autoantibodies in some patients.Most HA20 patients were reported to have nonsense mutations or shift mutations of TNFAIP3 gene, which leads to truncation of A20 protein, and only a small number of patients have missense mutation. In terms of treatment, anti-TNF treatment and anti-interleukin 1 is believed to be an effective and the most optimal therapy. The treatment effect is variable and requires long term observations. Conclusions: The clinical phenotypes of HA20 are complex. For patients with both autoinflammatory and autoimmune characteristics, family history should be inquired in detail and gene sequencing should be performed if necessary.

[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.