Development of Vogt-Koyanagi-Harada disease-like uveitis during treatment by anti-programmed death-1 antibody: a case report.

BACKGROUND: Several immune checkpoint inhibitors (ICIs) have been linked to the occurrence of Vogt-Koyanagi-Harada disease (VKHD)-like uveitis. Among the ICIs, there has been no report of immune-related adverse events (irAEs) caused by a new programmed death protein-1(PD-1) monoclonal antibody (Toripalimab). CASE PRESENTATION: This paper presents a case of VKHD-like uveitis that arose following Toripalimab therapy for urothelial cancer of the bladder, and the patient experienced symptoms 10 days after the final dosage of 20 months of medication treatment. This patient with bladder uroepithelial carcinoma had severe binocular acute panuveitis with exudative retinal detachment after receiving Toripalimab therapy. Binocular VKHD-like uveitis was suggested as a diagnosis. Both eyes recovered after discontinuing immune checkpoint inhibitors and local and systemic corticosteroid treatment. CONCLUSIONS: This report suggests that VKHD-like uveitis can also occur in patients receiving novel PD-1 antibodies and the importance of paying attention to eye complications in patients receiving treatment over a long period.

[Modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry for detection of cyclopiazonic acid in feeds].

Mycotoxins are toxic secondary metabolites produced by fungal species that can cause acute, subacute, and chronic toxicity in humans and animals. Thus, these toxins pose a significant threat to health and safety. Owing to the lack of effective antimold measures in the agricultural industry, feed ingredients such as corn, peanuts, wheat, barley, millet, nuts, oily feed, forage, and their byproducts are prone to mold and mycotoxin contamination, which can affect animal production, product quality, and safety. Cyclopiazonic acid (CPA), which is mainly biosynthesized from mevalonate, tryptophan, and diacetate units, is a myotoxic secondary metabolite produced by Penicillium and Aspergillus fungi. CPA is widely present as a copollutant with aflatoxins in various crops. Compared with some common mycotoxins such as aflatoxins, fumonisins, ochratoxins, zearalenones, and their metabolites, CPA has not been well investigated. In the United States, a survey showed that 51% of corn and 90% of peanut samples contained CPA, with a maximum level of 2.9 mg/kg. In Europe, CPA was found in Penicillium-contaminated cheeses as high as 4.0 mg/kg. Some studies have shown that CPA can cause irreversible damage to organs such as the liver and spleen in mice. Therefore, the establishment of a rapid and efficient analytical method for CPA is of great significance for the risk assessment of CPA in feeds, the development of standard limits, and the protection of feed product quality and safety. The QuEChERS method, a sample pretreatment method that is fast, simple, cheap, effective, and safe, is widely used in the analysis of pesticide residues in food. In this study, a modified QuEChERS method combined with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine CPA levels in feeds. The chromatographic separation and MS detection of CPA as well as the key factors affecting the extraction efficiency of CPA, including the type of extraction solvent, type of inorganic salt, and type and dosage of adsorbent, were optimized in detail. During the optimization of the chromatographic-separation step, the acid and salt concentrations of the mobile phase affected the separation and detection of CPA. During the optimization of the QuEChERS method, the addition of a certain amount of acetic acid improved the extraction efficiency of CPA because of its acidic nature; in addition, GCB and PSA significantly adsorbed CPA from the feed extract. Under optimal conditions, the CPA in the feed sample (1.0 g) was extracted with 2 mL of water and 4 mL of acetonitrile (ACN) containing 0.5% acetic acid. After salting out with 0.4 g of NaCl and 1.6 g of MgSO4, 1 mL of the ACN supernatant was purified by dispersive solid-phase extraction using 150 mg of MgSO4 and 50 mg of C18 and analyzed by UPLC-MS/MS. The sample was separated on a Waters HSS T3 column (100 mm×2.1 mm, 1.8 µm) using 2 mmol/L ammonium acetate aqueous solution with 0.5% formic acid and ACN as the mobile phases and then analyzed by positive electrospray ionization in multiple reaction monitoring mode. CPA exhibited good linearity in the range of 2-200 ng/mL, with a high correlation coefficient (r=0.9995). The limits of detection and quantification of CPA, which were calculated as 3 and 10 times the signal-to-noise ratio, respectively, were 0.6 and 2.0 µg/kg, respectively. The average recoveries in feed samples spiked with 10, 100, and 500 µg/kg CPA ranged from 70.1% to 78.5%, with an intra-day precision of less than 5.8% and an inter-day precision of less than 7.2%, indicating the good accuracy and precision of the proposed method. Finally, the modified QuEChERS-UPLC-MS/MS method was applied to the analysis of CPA in 10 feed samples obtained from Wuhan market. The analysis results indicated that the developed method has good applicability for CPA analysis in feed samples. In summary, an improved QuEChERS method was applied to the extraction and purification of CPA from feeds for the first time; this method provides a suitable analytical method for the risk monitoring, assessment, and standard-limit setting of CPA in feed samples.

IL-17A and TNF-α inhibitors induce multiple molecular changes in psoriasis.

Adalimumab and secukinumab are commonly used for moderate to severe psoriasis vulgaris (PV). Although distinct individual responses to and impaired effectiveness of these biological agents occur occasionally, little is known about the underlying reasons. Here, we report a proteomic analysis of psoriatic lesions from patients treated with these drugs using data-independent acquisition mass spectrometry (DIA-MS). Thousands of differentially expressed proteins (DEPs) changed over 12 weeks of treatment. Network analysis showed that DEPs could interact and induce transformation in matrix components, metabolic regulation, and immune response. The results of parallel reaction monitoring (PRM) analysis suggested that S100s, STAT1, KRT2, TYMP, SOD2, HSP90AB1, TFRC, and COL5A1 were the most significantly changed proteins in both groups. There was a positive association between the Psoriasis Area and Severity Index (PASI) score and three proteins (TFRC, IMPDH2, KRT2). Our study findings suggest that inhibition of IL-17A and TNF-α can induce changes in multiple molecules in psoriatic lesions and have an overlapping influence on the immune response and process through direct or indirect effects.

Transition-metal-free synthesis of aryl 1-thioglycosides with arynes at room temperature.

A mild, convenient and transition-metal-free protocol for the synthesis of aryl 1-thioglycosides is presented via arynes generated in situ combined with glycosyl thiols in the presence of TBAF(tBuOH)4. The methodology provides a general and efficient way to prepare a series of functionalized thioglycosides in good to excellent yields with a perfect control of the anomeric configuration at room temperature. In addition, the reaction conditions tolerate a variety of the pentoses and hexoses, and the reaction also performs smoothly on protected monosaccharides and disaccharides.

EncephalApp Stroop App predicts poor sleep quality in patients with minimal hepatic encephalopathy due to hepatitis B-induced liver cirrhosis.

BACKGROUND/AIM: A novel computerised Stroop test- EncephalApp Stroop App (EncephalApp) has good diagnostic validity for minimal hepatic encephalopathy (MHE) in cirrhotic patients. The Stroop test is correlated with sleep disturbances which are common, and severely affects health-related quality of life in cirrhotic patients with MHE. We evaluated the relationship between sleep quality and EncephalApp results in patients with MHE due to hepatitis B-induced liver cirrhosis. PATIENTS AND METHODS: We enrolled 180 adult patients with hepatitis B-induced cirrhosis. All patients were tested using the psychometric hepatic encephalopathy score (PHES) and EncephalApp. We analysed the diagnostic validity of EncephalApp for MHE using PHES as the gold standard for reference. The sleep quality of included patients was evaluated using the Pittsburgh Sleep Quality Index (PSQI). The predictive factors for poor sleep quality were analysed using backwards conditional stepwise logistic regression analysis. RESULTS: Ninety-eight patients (54.4%) were diagnosed with MHE by PHES. Receiver operating characteristic (ROC) curve analysis showed that the threshold value of EncephalApp for MHE diagnosis was 225.60 s. EncephalApp showed 85.2% sensitivity and 77.3% specificity for diagnosing MHE; the area under the ROC curve was 0.864. PSQI scores of cirrhotic patients with MHE were significantly lower than those without MHE (P < 0.05). Child Turcotte Pugh grades (Odds ratio [OR] = 2.11 [1.55-2.85], P < 0.01) and the total Off-time plus On-time of EncephalApp (OR = 4.14 [1.95-6.29], P < 0.01) were independent predictors of poor sleep quality in MHE patients. CONCLUSIONS: The total Off-time plus On-time of EncephalApp predicts poor sleep quality in patients with MHE due to hepatitis B-induced cirrhosis.

Treatment of Thoracolumbar Fractures Through Different Short Segment Pedicle Screw Fixation Techniques: A Finite Element Analysis.

OBJECTIVE: To compare the von Mises stresses of the pedicle screw system and the displacement of injured vertebrae using 3-D finite element analysis, and to evaluate the curative effect of the pedicle screw system. METHODS: Finite element methods were used for biomechanical comparison of four posterior short segment pedicle screw fixation techniques. The different pedicle screw models are traditional trajectory (TT), Universal Spine System (USS), cortical bone trajectory (CBT), and CBT at the cranial level and pedicle screw (PS) at the caudal level (UP-CBT). The stress distribution of the screws and connecting rods under different working conditions and the displacement of the injured vertebrae were compared and analyzed. RESULTS: After the pedicle screw system was fixed, the stress under vertical compression was mainly concentrated at the proximal end of the screw, while the stress was mainly concentrated on the connecting rod during flexion, extension, lateral flexion, and rotation. The TT group had the greatest stress during the flexion, extension, and left and right rotation. The UP-CBT group was most stressed when the left and right sides were flexed; the stress of the USS screw system was less than that of the other three models during flexion, lateral flexion, and rotation. The maximum von Mises stress values of pedicle screws in all exercise states were 556.2, 340.7, 458.1, and 533.4 MPa, respectively. In the USS group, the displacement of the injured vertebra was small in the flexion, and the left and right lateral flexion and the right rotation were higher than in the TT group and the CBT group. The maximum displacements of the injured vertebrae in all motion states were 1.679, 1.604, 1.752, and 1.777 mm, respectively. CONCLUSION: Universal Spine System pedicle screws are relatively less stressed under different working conditions, the risk of breakage is small, and the model is relatively stable; CBT screws do not exhibit better mechanical properties than conventional pedicle screws and USS pedicle screws.

Effect of prophylactic intraocular pressure-lowering medication (brinzolamide) on intraocular pressure after ranibizumab intravitreal injection: A case-control study.

PURPOSE: To observe the effect of prophylactic intraocular pressure (IOP)-lowering medication (brinzolamide) on IOP after ranibizumab intravitreal injections (IVIs). MATERIALS AND METHODS: This prospective case-control study included 352 eyes from 352 patients (1 eye per patient) who were treated with ranibizumab intravitreal injection and divided randomly into two groups. Two hundred and three patients in control group only received the ranibizumab IVI, but 149 patients in case group received one drop of prophylactic intraocular brinzolamide preinjection. The IOP was measured by noncontact tonometer before injection, at 10, 30, 120 min and 1 day after injection in a sitting position. RESULTS: The mean IOP measured before injection, at 10, 30, 120 min and 1 day after injection individually were 15.79 ± 2.21 mmHg, 19.33 ± 4.86 mmHg, 16.64 ± 2.93 mmHg, 16.17 ± 3.13 mmHg, and 15.07 ± 2.55 mmHg in case group and were 15.82 ± 2.57 mmHg, 21.34 ± 5.88 mmHg, 18.17 ± 4.06 mmHg, 17.59 ± 4.42 mmHg, and15.48 ± 2.92 mmHg in control group. Comparing two groups, the mean increase on IOP was statistically significant at 10, 30, 120 min postinjection (P < 0.05). CONCLUSIONS: IVI of ranibizumab causes a considerable short-term transient rise on IOP in most patients. The effect of prophylactic IOP-lowering medication on IOP after IVIs can be statistically significant from 10 min to 2 h after IVIs.

Core decompression treatment of early-stage osteonecrosis of femoral head resulted from venous stasis or artery blood supply insufficiency.

BACKGROUND: The objective of this study was to explore the therapeutic effect of core decompression on different hemodynamics changes associated with osteonecrosis of the femoral head (ONFH). METHODS: A total of 67 patients with 76 hips suffering from ONFH (Arco stage I-IIC) received core decompression surgical procedure. Radiographic, magnetic resonance imaging, and digital subtraction angiography examinations were performed before operation. Radiographic and magnetic resonance imaging follow-ups were also performed after 12, 24, and 60 mo of operation. Clinical follow-ups were performed using the Harris Hip Score (HHS) for an average period of 5 y postoperation. RESULTS: The mean follow-up time ranged from 2-8 y with an average of 5 y. Two hips were lost during follow-up. Successful clinical efficacy (HHS ≥80) was achieved in 91.9% (68/74) of the hips. Six hips had conversion to total hip arthroplasty (THA), one hip had venous stasis, and five hips had both vein stasis and artery blood supply insufficiency. The mean HHS for the patients who did not have conversion to THA improved from 65 ± 3.5 to 89 ± 3.6 (mean ± standard deviation). Twenty-six stage I hips (100%), 22 of 23 stage IIA hips (95.7%), 13 of 15 stage IIB hips (86.7%), and 8 of 10 stage IIC hips (80%) had successful outcomes with no surgical complications. Kaplan-Meier survival analysis showed that 8-y survival rate was significantly different between stage I and stage IIC (THA as an end point; P < 0.001). CONCLUSIONS: In patients with early-stage ONFH resulted from only venous stasis, core decompression led to a significant improvement in HHS and 8-y survival rate. However, the long-term efficacy for ONFH associated with artery blood supply insufficiency was not encouraging. Therefore, preoperative digital subtraction angiography is necessary before performing core decompression.

Effect of superior retinacular artery damage on osteonecrosis of the femoral head.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is the result of dysfunctional blood supply, but associations between specific damaged arteries, imaging changes and clinical sign require more understanding. We investigated characteristics of ONFH that pertain to blood supply, imaging appearance, and clinical feature to judge the prognosis of ONFH. METHODS: Clinical data were collected for 92 patients (118 hips) with ONFH, including gender, age, duration of pain (from initial clinical presentation to arthroplasty), cause, stage, and classification. Magmatic resonance imaging and X-rays were obtained of all patients to diagnose ONFH. The sizes of lesions were classified by necrotic index. The location of necrosis was classified as Type A, B, or C using the grading system by magmatic resonance imaging and X-rays. All hips were imaged with digital subtraction angiography to visualize their blood-supply characteristics. Hips were divided into groups based on the source artery for femoral head damage: superior retinacular artery (S), inferior retinacular artery (I), and combined superior and inferior retinacular arteries (S+I). Via digital subtraction angiography, imaging appearances and clinical data in three groups were compared. RESULTS: ONFH was caused by damage in either the superior or inferior retinacular artery, or both, in all of 118 hips. The group with only inferior retinacular artery damage reported longer hip pain duration than the other groups. The probability of the lesion extending laterally to the acetabular edge in group S was much more than it in group I. Necrosis indices of the patients in S and S+I were higher than those in group I. CONCLUSIONS: ONFH associated with interruption of the superior and inferior retinacular arteries in this study. When the former alone was damaged, the necrosis of the volume was larger, the risk of femoral head collapse was higher and the time from initial clinical presentation to arthroplasty was shorter.

Prospective and comparative analysis of internal fixation of femoral neck fractures with or without vascularized iliac graft in young adults.

The purpose of this study was to compare the effectiveness of 2 surgical approaches for femoral neck fractures in young adults: internal fixation with or without a vascularized iliac graft. Between January 1998 and December 2008, seventy-eight patients presented with a Garden type III (n=38) or IV (n=40) femoral neck fracture. Thirty-eight patients were women and 40 were men, with an average age of 28 years (range, 16-38 years). Fractures were caused by fall injury (n=24), motor vehicle accident (n=36), and heavy weight lifting (n=18). Patients were randomly divided into 2 groups. Group A underwent internal fixation with 2 cannulated compression screws combined with an iliac graft supported by the ascending branch of the lateral femoral circumflex artery (n=44), and group B underwent internal fixation with 3 cannulated compression screws (n=34). Average follow-up was 4.5 years (range, 2-8 years), and mean Harris Hip Score was 92 (range, 62-100) in group A and 84 (range, 40-100) in group B. Average fracture healing time at final follow-up was 4.4 months in group A and 6 months in group B. Two (4.5%) cases of osteonecrosis of the femoral head occurred in group A, and 8 (23.5%) cases occurred in group B. Internal fixation with 2 cannulated compression screws combined with an iliac graft supported by the ascending branch of the lateral femoral circumflex artery is an effective surgical approach for treating femoral neck fractures in young adults to minimize the occurrence of fracture nonunion and osteonecrosis of the femoral head and to facilitate bone healing and functional recovery of the hip.

[Retinal thickness of laser radiating zone after photodynamic therapy].

OBJECTIVE: To observe changes of retinal thickness after photodynamic therapy (PDT) for patients with subfoveal choroidal neovascularization (CNV), and evaluate the effect of retinal edema after PDT. METHODS: PDT was performed on 27 eyes of 25 patients with subfoveal CNV, the spot diameter of laser beam was 1.8 - 4.3 mm (average 2.9 mm), OCT was used to evaluate the changes of retinal thickness including the retinal thickness of macular fovea and 3 mm laser radiating zone 24 hour 1 week, 1 month, 3 month after PDT. Retinal thickness was compared before PDT and 24 h, 1 week, 1 month, 3 month after PDT respectively. RESULTS: Retinal thickness of fovea before PDT and 24 h, 1 week, 1 month, 3 month was (278.07 +/- 85.31), (324.52 +/- 96.08), (242.74 +/- 67.40), (234.26 +/- 51.04) microm and (239.73 +/- 52.81) microm respectively, the average retinal thickness of 3 mm laser radiating zone was (266.71 +/- 60.82), (309.25 +/- 82.69), (257.48 +/- 52.48), (245.44 +/- 47.54) microm and (244.88 +/- 44.22) microm respectively. There was statistical significance before PDT compared with 24 h, 1 month, 3 month after PDT (P < 0.01). CONCLUSIONS: The result of our study indicate that retinal thickness of laser radiating zone increases apparently 24 h after PDT and regresses during the first week. It suggest that retinal edema after PDT may due to the leakage from the CNV, increased permeability in choroid and retina of laser radiating zone, and transient dysfunction of retinal pigment epithelial cells.

[Establishment of a mouse model of cyclophosphamide-induced thrombocytopenia and determination of platelet function in this model].

OBJECTIVE: To establish a mouse model of acute hematopoietic failure and explore the pathological basis of platelet changes in bone marrow suppression. METHODS: An initial large dose of cyclophosphamide (200 mg/kg) was injected through the tail veins of the mice, follow by daily intraperitoneal injection starting on the next day for 7 d. The number and morphology of the cells in the peripheral blood and bone marrow were observed by means of cell counting and smear, respectively, with the platelet aggregation determined using ADP. The coagulation time was measure by turbidimetry. RESULTS: The amount of platelets, erythrocytes, leukocytes and the nucleated cells in mice bone marrow was significantly lowered in the mouse models in comparison with the control mice, and the normal hematopoietic tissues were depressed. The blood platelets in the models were lowered by 49%, an amplitude of declination significantly greater than that occurring in the erythrocytes and leukocytes (by 28% and 25% respectively). Though the mean platelet volume and percent platelet aggregation underwent no obvious changes, the coagulation time was significantly shortened. CONCLUSION: The methods we described for establishing mouse models of hematopoietic failure induced by cyclophosphamide is rapid and highly efficient, and may facilitate ready preparation of mouse models of thrombocytopenia which respond strongly to cyclophosphamide without blood platelets function impairment.