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Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs).A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool.In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-a inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P 0.001); higher risk of URTI for TNF-a inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P = 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-a inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P = 0.006).This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Background: Damage of the medial prefrontal cortex (mPFC) results in similar characteristics to the cognitive deficiency seen with the progress of Parkinson’s disease (PD). Since the course of mPFC damage is still unclear, our study aimed to investigate the effects of melatonin (MT) on neurotoxicity in the mPFC of a rat model of PD. Methods: One hundred and fifty-four normal, male Wistar rats were randomly divided into the following five groups: normal + normal saline (NS), normal + 6-hydroxydopamine (6-OHDA), sham pinealectomy (PX) + 6-OHDA, PX + 6-OHDA, and MT + 6-OHDA. 6-OHDA was injected into the right substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of each group, except normal + NS, 60 days after the PX. In the MT treatment group, MT was administered immediately after the intraperitoneal injection at 4 p.m. every day, for 14 days. Neuronal apoptosis in the mPFC was examined using the TUNEL method, while the expression of tyrosine hydroxylase (TH), Bax, and Bcl-2 in this region was measured using immunohistochemistry. The concentration of malondialdehyde (MDA) in the mPFC was examined using the thiobarbituric acid method. Results: Rats in the normal + 6-OHDA and sham PX + 6-OHDA groups were combined into one group (Group N + 6-OHDA) since there was no significant discrepancy between the groups for all the detected parameters. Apoptosis of cells in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups was successively significantly increased (Hc = 256.25, P < 0.001). The gray value of TH (+) fibers in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups was also successively significantly increased (F = 99.33, P < 0.001). The staining intensities of Bax and Bcl-2 were as follows: Group NS +/+, Group MT + 6-OHDA ++/+, Group N + 6-OHDA ++/+, and PX + 6-OHDA +++/+. The concentrations of MDA in the NS, MT + 6-OHDA, N + 6-OHDA, and PX + 6-OHDA groups were significantly increased in sequence (Hc = 296.309, P < 0.001). Conclusions: Neuronal damage of the VTA by 6-OHDA might induce VTA-mPFC nerve fibers to undergo anterograde nerve damage, in turn inducing transneuronal damage of the mPFC. PX significantly exacerbated the neurotoxicity in the mPFC, which was induced by the neuronal injury of the VTA. However, MT replacement therapy significantly alleviated the neurotoxicity in the mPFC. Key words: Medial Prefrontal Cortex; Melatonin; Pinealectomy; Tyrosine Hydroxylase; Ventral Tegmental Area

Background: A large proportion of the patients with papillary thyroid microcarcinoma are young women. Therefore, minimally invasive endoscopic thyroidectomy with central neck dissection (CND) emerged and showed well-accepted results with improved cosmetic outcome, accelerated healing, and comforting the patients. This study aimed to evaluate the safety and effectiveness of robotic total thyroidectomy with CND via bilateral axillo-breast approach (BABA), compared with conventional open procedure in papillary thyroid microcarcinoma. Methods: One-hundred patients with papillary thyroid microcarcinoma from March 2014 to January 2015 in Jinan Military General Hospital of People's Liberation Army (PLA) were randomly assigned to robotic group or conventional open approach group (n = 50 in each group). The total operative time, estimated intraoperative blood loss, numbers of lymph node removed, visual analog scale (VAS), postoperative hospital stay time, complications, and numerical scoring system (NSS, used to assess cosmetic effect) were analyzed. Results: The robotic total thyroidectomy with CND via BABA was successfully performed in robotic group. There were no conversion from the robotic surgeries to open or endoscopic surgery. The subclinical central lymph node metastasis rate was 35%. The mean operative time of the robotic group was longer than that of the conventional open approach group (118.8 ± 16.5 min vs. 90.7 ± 10.3 min, P < 0.05). The study showed significant differences between the two groups in terms of the VASs (2.1 ± 1.0 vs. 3.8 ± 1.2, P < 0.05) and NSS (8.9 ± 0.8 vs. 4.8 ± 1.7, P < 0.05). The differences between the two groups in the estimated intraoperative blood loss, postoperative hospital stay time, numbers of lymph node removed, postoperative thyroglobulin levels, and complications were not statistically significant (all P > 0.05). Neither iatrogenic implantation nor metastasis occurred in punctured porous channel or chest wall in both groups. Postoperative cosmetic results were very satisfactory in the robotic group. Conclusions: Robotic total thyroidectomy with CND via BABA is safe and effective for Chinese patients with papillary thyroid microcarcinoma who worry about the neck scars.

Moreover, the prognosis of patients diagnosed with grade III gliomas varies significantly. In this study, we assessed the factors that contribute to the prognosis of patients with grade III gliomas. Methods Data from 97 patients with grade III glioma who received surgery from 2000 to 2005 were included in this study. Kaplan-Meier survival analysis and Cox regression analysis were used to analyze the prognostic effects of 16 different factors selected from clinical characteristics, results from neuroimaging and pathological examinations, as well as different treatment schemes. Results The results indicated that age, preoperative Karnofsky Performance Scale score, extent of tumor invasion, tumor resection degree, residual tumor shown by postoperative magnetic resonance imaging (MRI), and postoperative radiotherapy and chemotherapy all correlated with patient prognosis. Furthermore, Cox multivariate analysis also showed the age ( P

Ankylosing spondylitis (AS), which primarily affects the sacroiliac joints, spine, and enthuses, is a chronic inflammatory rheumatic disorder. Acute anterior uveitis is the most common ophthalmologic involvement, whereas optic neuritis (ON) rarely coexists with AS.[1] ON is an immune-mediated inflammation of the optic nerve, which could be the initiated symptom of multiple sclerosis (MS) or neuromyelitis optica (NMO). Bilateral simultaneous ON with long enhanced optic nerve lesions in magnetic resonance imaging (MRI) was considered as features of NMO spectrum disorders (NMOSDs). However, comprehensive review of the current literature showed little evidence of AS as an accompanied autoimmune condition in NMO,[2] and the specific biomarker aquaporin-4 antibody (AQP4-Ab) was negative in our patient. In the current report, we present the first case of ON with active AS in a Chinese male patient. The association between the two diseases remains to be evaluated. A male patient aged 31 years suffered sudden decreased vision in two eyes without ocular pain. The vision loss began with central scotoma and darkened in the whole visual field, equivalent in the two eyes, and quickly progressed to no-light-perception (NLP) in several hours. The immediate fundus examination revealed slight swelling optic disc with normal retina. Symmetrical thickening of temporal peripapillary retinal nerve fiber layer was revealed by optical coherence tomography. Fundus fluorescence angiography showed mild fluorescence of the optic disc in a later phase. The initial diagnosis of bilateral ON was made. However, no efficient treatment was given by the local hospital. Twenty days later, the patient came to us with bilateral pale optic discs. Visual acuity (VA) in the right eye was light-perception while in the left eye was still NLP. Bilateral mydriasis was found, and the relative afferent papillary defect was positive in the left pupil. Flash-visual evoked potential of the two eyes showed severely decreased amplitude of P100 while bilateral electroretinogram was normal. Brain, cervical thoracic and orbital MRI were performed and showed bilateral optic nerves enlargement, T2 hyperintensity, and gadolinium enhancement [Figure 1]. Figure 1 The image evidences of optic neuritis in our clinic (20 days after onset). The appearance of optic discs were pale with blurred border in both right (a) and left (b) eyes; (c) Orbital magnetic resonance imaging showed gadolinium enhancement in bilateral ... Blood tests showed greatly increased C-reaction protein (CRP) of 107 mg/L (normal range: 0–8 mg/L), erythrocyte sedimentation rate (ESR) of 88 mm/h (normal range: 0–15 mm/h), and strong positive HLA-B27 (98%, normal range: 0–7.14%). The examination of serum used the best available method (cell-based assay) revealed negative AQP4-Ab. The results of other serologic testing of antinuclear antibody spectrum, anti-neutrophil cytoplasmic antibody, rheumatoid factor, anticardiolipin antibody, angiotensin converting enzyme, syphilitic serologic test, and paraneoplastic tests were all negative. Lumbar puncture was performed and showed normal cerebral-spinal fluid (CSF) in the routine tests, including the cell count and protein concentration, as well as negative oligoclonal bands. The patient's father had a history of AS for 20 years. The diagnosis of AS was confirmed for the patient himself 10 months ago according to the New York criteria.[1] He received nonsteroidal anti-inflammatory drugs and sulfasalazine irregularly, together with intraarticular injection of corticosteroid to control the symptoms. When the visual symptoms occurred, bilateral gonarthritis was found. The severe back pain lasted and the morning stiffness prolonged from several minutes to more than 0.5 h. Exudation of bilateral knee joints cavity and bilateral sacroiliitis of grade 2 were revealed by ultrasonography and computed tomography, respectively. The significantly elevated ESR and CRP, combined with a Bath Ankylosing Spondylitis Disease Activity Index of 5.5 indicated the co-existed active AS. The patient was treated with intravenous methylprednisolone, which began with 1 g for 3 days, then followed by oral 1 mg/kg for 10 days and tapered. VA in the right eye improved to hand move when discharged and to 0.02 after our follow-up period of 2 years, but VA in the left eye was continuously NLP. Eye inflammation in AS is largely restricted to the uvea. To date, the co-existed AS and ON were only reported in three cases, but no reaction of AS was observed during ON onset. ON could be the initiated symptoms of MS. The typical ON with the unilateral visual loss, eye pain in movement, and spontaneously recovery will develop to MS in 50% after 15 years according to the results of the ON treatment trial. Nevertheless, the atypical clinical appearance of bilateral eyes involved, optic disc edema, and severe visual loss without eye pain were considered as having lower risks for developing MS. Co-existence of MS and AS was reported in several cases,[3] but the mechanics were still uncertain. A peptide of myelin basic protein was reported to be a ligand of HLA-B27 and both AS and MS may share the similar pathologic pathway of activation of T lymphocytes with the environmental factors. Besides, a causal association between anti-tumor necrosis factor (TNF)-α blockers (infliximab, etanercept, and adalimumab, etc.), which target the overexpressed TNF-α in sacroiliac joints and widely employed against AS, and onset of MS or ON may exists.[4] Yet, our patient had no history of using anti-TNF-α medicine. Moreover, atypical ON was showed in this case, and CSF was negative for intrathecal production of oligoclonal bands, which may indicate non-MS mediated etiology. Atypical ON may indicate a high prevalence of serum AQP4-Ab, and ON with seropositive AQP4-Ab was covered in the term of NMOSDs. The diagnostic criteria of NMOSDs including classical NMO and some limited forms, which may have the same pathogenesis mechanisms of astrocyte damage with complement and antibody mediated cytotoxicity. Serum AQP4-Ab, known as NMO-IgG, the presence of which was over 70% sensitive and 100% specific by cell-based assay for clinically defined NMO,[5] is critical in distinguishing NMO related ON from MS. Moreover, 10–25% of patients clinically diagnosed with NMO are seronegative for AQP4-IgG. Hence, extended follow-up in our patient was necessary. In conclusion, this is the first case of severe bilateral ON with active AS. Further investigations should be made in the ON population of China and may provide more clinical evidences for this phenomenon. Financial support and sponsorship This work is supported by the National “863” Plan Biological and Medical Technology Project “Development of equipments in diagnosis and visual function evaluation for optic neuritis” (No. 2015AA020511). Conflicts of interest There are no conflicts of interest.

To the Editor: Right pulmonary artery-left atrial fistula (RPALAF) is an extremely rare congenital cardiovascular malformation that may be difficult to diagnose by clinical symptoms. High resolution computed tomographic (CT) gives a clear view of cardiovascular and can provide an accurate diagnosis, and it has not been reported in the last literature date though 320-slice CT scan giving these clear views. On the base of a case of this disease, we describe an 18-year-old girl with RPALAF confirmed by 320-slice CT. This case demonstrates that the 320-slice CT scan is a sensitive and reliable technique for establishing the diagnosis of RPALAF when it cannot be visualized by clinical symptoms.

To the Editor: The dramatic expansion of an esophagus is extremely rare in esophageal diseases. We present a case of megaesophagus associated with atelectasis of the right lung, which showed a typical of achalasia with a “bird's beak appearance”. In order to palliate patient's symptoms, two gastric tubes used. One was inserted into the esophagus for suction residual chymus, the other was inserted into the stomach for supplying nutrition. However, after the symptoms eased, she refused all further treatment. A 53-year-old woman was hospitalized because of dysphagia for 13 years with squeezing chest pain and retrosternal obstruction. This symptom could be alleviated after vomiting. She suffered from fever (highest 40°C) with chilly and shivering after eating for a week. Physical examination disclosed that breath sound in the right lung was lower than the left lung, cardiac rhythm and heart sound were normal. Upper gastroenterography showed that a large area of patchy shadows on the right chest, upper esophagus was expanded, with an unsmooth inner wall. No barium was in the stomach [Figure 1a]. The gastroscope examination showed that the inner diameter of upper segment of esophagus was expanded obviously, and the entrance of cardia (ostiumcardiacum) became narrow which it was hard to pass with gastroscope [Figure ​[Figure1b1b and ​and1c].1c]. Sixteen-slice computed tomography scan revealed the middle lobe of right lung was detected atelectasis in lung window because of compression from enlarged esophagus, and upper esophagus expanded obviously [Figure 1d], lower esophagus and cardia became significantly narrow and mucous membrane around of this area also was thick in soft tissue window. Due to infection caused by corruption of chyme deposited in esophagus, we decided to alleviate symptoms of obstruction (two gastric tubes were used, one was inserted into the esophagus for suction residual chymus, the other was inserted into the stomach for supplying nutrition), and antibiotics was used at the same time as another main treatment. However, after the symptoms eased, she refused all further treatment. Figure 1 Barium meal X-ray examination showed a dilated esophagus with tapering at the distal end. This tapering is often referred to as “bird's beak appearance” and is typical of achalasia and a large area of patchy shadows on the right chest ... It is so serious that can result in lung atelectasis and aspiration pneumonia. These cases have been reported sudden death secondary to megaesophagus.[1] Esophageal achalasia is a comparatively rare disease which usually presents with esophageal motility dysfunction characterized by failure of esophageal peristalsis and lack of relaxation of the lower esophageal sphincter. The incidence of esophageal achalasia is approximately 1/100,000 annually.[2]: Drug treatment is not effective, surgical procedure is most widely used to treat esophageal achalasia, while the conventional surgical injury is severe. Pneumatic dilation, laparoscopic Heller myotomy with fundoplication and per oral endoscopic myotomy has since become more popular due to less invasive and a similar outcome.[3] Two gastric tubes were used in this patient palliated patient's symptoms, improved the quality of life, and got a satisfactory preliminary status. However, after the symptoms eased, she refused a subsequent surgical treatment.

The ADRA2B gene insertion/deletion (I/D) polymorphism is associated with various cardiovascular and metabolic phenotypes. Large (C1) and small (C2) artery compliance, assessed by pulse wave analysis, is considered as sensitive markers or risk factors for cardiovascular disease. Therefore whether the ADRA2B I/D polymorphism is associated with C1 and C2 need to be investigated.A total of 227 men and 243 women were enrolled in a Chinese family-based study. C1 and C2 were measured by pulse wave analysis. ADRA2B genotypes were determined by polymerase chain reaction. Statistical methods included generalized estimation equations and quantitative transmission disequilibrium test.The II (31.9%), ID (46.8%) and DD (21.3%) genotype frequencies were in Hardy-Weinberg equilibrium (P = 0.73). The covariates selected by stepwise regression for C1 and C2 were age, systolic pressure and gender. The population based association analysis showed that C1 and C2 were not associated with ADRA2B genotype both before (C1: P = 0.28; C2: P = 0.27) and after (C1: P = 0.58; C2: P = 0.18) the adjustment. The family-based analyses of 128 informative offspring showed that transmission of the D-allele was not associated with C1 or C2, both before (C1: P = 0.42; C2: P = 0.85) and after (C1: P = 0.31; C2: P = 0.82) the adjustment.The study do not support that the ADRA2B gene I/D polymorphism has a major gene effect on C1 or C2 in the Chinese population of current sample size.