Intraoperative Complications and Perioperative and Surgical Outcomes of Single-Port Robotics-Assisted Sacrocolpopexy.

INTRODUCTION AND HYPOTHESIS: The objective was to assess intraoperative and postoperative complication rates, along with perioperative and surgical outcomes, following single-port robotics-assisted sacrocolpopexy. METHODS: This retrospective case series included 200 patients who underwent single-port robotics-assisted sacrocolpopexy to treat Pelvic Organ Prolapse Quantification (POPQ) stage 2-4 symptomatic prolapse between April 2020 and August 2023 by a single surgeon. Intraoperative and postoperative complications and perioperative outcomes were evaluated for all the patients, whereas surgical outcomes for 74 patients were assessed at 1-year follow-up. Surgical failure was defined as the presence of any of the following: the presence of vaginal bulging symptoms, any prolapse beyond the hymen, or retreatment for prolapse. RESULTS: During the study period, 200 single-port robotics-assisted sacrocolpopexies were performed. The median age and body mass index were 65.0 years and 24.6 kg/m2 respectively. Most patients had POPQ stage 3 or 4 prolapse and underwent concomitant total hysterectomy. The median total operation time was 212.0 min, and none of the patients required conversion to laparoscopy or laparotomy. The intraoperative cystotomy rate was 2.5%, and one patient had a blood transfusion owing to presacral vessel injury. Postoperative complications of mesh exposure and wound hernia were 0.5% and 2.0% respectively. At 1 year postoperatively, the rate of composite surgical failure was 9.5%, with a 5.4% anatomical recurrence rate. None of the patients experienced apical prolapse recurrence, and one received anterior colporrhaphy for anterior compartment prolapse recurrence. CONCLUSIONS: Single-port robotics-assisted sacrocolpopexy is safe and effective, with low complication rates and favorable perioperative and surgical outcomes.

Effect of Corneal and Lens Eccentricity Difference on Rigid Corneal Lens Treatment in Patients With Keratoconus.

OBJECTIVE: To evaluate the effects of rigid corneal lenses (RCL) in patients with keratoconus, based on eccentricity. METHODS: Eighty-four eyes from 84 patients were included in this retrospective comparative study. Based on the median value of eccentricity difference between the cornea and back surface of the RCL, the patients were divided into groups 1 (<0.08) and 2 (≥0.08). Visual acuity, refractive index, and corneal topography indices were compared before and three months after lens use. RESULTS: Visual acuity, astigmatism, refractive error, corneal curvature, and corneal thickness improved significantly in both groups. Apical power and anterior elevation improved significantly in group 1, with small differences in eccentricity, but not in group 2. Changes in apical power before and after lens use were significantly different between the two groups. CONCLUSION: The RCL was effective for the cornea of keratoconus, especially when the prescription was made with a small difference in eccentricity.

Key mutations in the spike protein of SARS-CoV-2 affecting neutralization resistance and viral internalization.

To control the ongoing COVID-19 pandemic, a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines have been developed. However, the rapid mutations of SARS-CoV-2 spike (S) protein may reduce the protective efficacy of the existing vaccines which is mainly determined by the level of neutralizing antibodies targeting S. In this study, we screened prevalent S mutations and constructed 124 pseudotyped lentiviral particles carrying these mutants. We challenged these pseudoviruses with sera vaccinated by Sinovac CoronaVac and ZF2001 vaccines, two popular vaccines designed for the initial strain of SARS-CoV-2, and then systematically assessed the susceptivity of these SARS-CoV-2 variants to the immune sera of vaccines. As a result, 14 S mutants (H146Y, V320I + S477N, V382L, K444R, L455F + S477N, L452M + F486L, F486L, Y508H, P521R, A626S, S477N + S698L, A701V, S477N + T778I, E1144Q) were found to be significantly resistant to neutralization, indicating reduced protective efficacy of the vaccines against these SARS-CoV-2 variants. In addition, F486L and Y508H significantly enhanced the utilization of human angiotensin-converting enzyme 2, suggesting a potentially elevated infectivity of these two mutants. In conclusion, our results show that some prevalent S mutations of SARS-CoV-2 reduced the protective efficacy of current vaccines and enhance the infectivity of the virus, indicating the necessity of vaccine renewal and providing direction for the development of new vaccines.

PTH level might be associated with impaired quality of life in patients with nonsurgical hypoparathyroidism.

OBJECTIVE: Nonsurgical hypoparathyroidism (ns-HP) is a rare disease. There are few studies on Quality of Life (QoL) among patients with ns-HP. This study aimed to investigate the QoL among ns-HP patients with regular conventional treatment, and explore the influence factors affecting QoL among these Chinese ns-HP patients. METHODS: This is a cross-sectional study comparing 101 patients identified as ns-HP and 101 healthy controls. The questionnaires of Short Form 36 Health Survey questionnaire version 2(SF-36v2) were used to evaluate QoL. RESULTS: Scores of all eight subdomains of SF-36v2 and physical component scores (PCS), mental component scores (MCS) were significantly lower in the ns-HP group compared with the healthy controls. The indices of all subdomains of SF-36v2 between Q1 (the lowest quartile) and Q4 (the highest quartile) groups were compared, suggesting higher percentages of detectable parathyroid hormone (PTH) before treatment in Q4 group among all QoL indices except two subdomains (physical function and body pain). CONCLUSION: Both mental and physical QoL were impaired in the ns-HP patients even with regular conventional treatment for hypocalcemia, which were more severe in cases with lower baseline PTH levels.

Compressive optic neuropathy due to posterior ethmoid mucocele.

Mucoceles are cystic formations characterized by the presence of mucus-secreting epithelial cells, which enlarge when the excretory duct becomes obstructed. Posterior ethmoidal mucoceles are rare conditions that can lead to severe ocular complications requiring immediate intervention. The close anatomical proximity of posterior ethmoidal mucoceles to the optic nerve underscores their significance. In this case report, we present a case of rapidly progressing compressive optic neuropathy secondary to a posterior ethmoidal mucocele. A previously healthy forty-six-year-old woman presented with sudden visual loss in her left eye, preceded by left-sided headache and periorbital pain. Clinical examination and imaging studies revealed an oval-shaped mass within the posterior ethmoid cell compressing the left optic nerve. Emergency surgery was performed to alleviate optic nerve compression, which successfully relieved periocular pain. However, the patient's visual acuity and visual field defect remained unchanged postoperatively. Thinning of the ganglion cell layer in the macula region was observed during follow-up examinations. The role of corticosteroids and antibiotics in visual rehabilitation and the impact of delayed surgical decompression on visual outcome remain subjects of debate. Additional cases of mucocele-associated optic neuropathy should be published and analyzed to establish optimal treatment approaches.

[The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition].

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

[The 499th case: Roux-en-Y gastric bypass, limb weakness, and ostealgia].

A 36-year-old woman was admitted to the Peking Union Medical College Hospital with a history of fractures for 2 years, limb weakness for 1 year, and ostealgia for 2 months. The patient's examination identified iron deficiency anemia, significantly decreased serum calcium and 25-hydroxyvitamin D3 levels, and increased alkaline phosphatase and parathyroid hormone levels. Imaging showed several typical signs of osteomalacia. Considering the history of Roux-en-Y gastric bypass surgery, the diagnosis was considered to be osteomalacia caused by a postoperative nutritional absorption disorder. The patient was supplemented with calcitriol, calcium, and vitamin D and gradually returned to normal physical activity. The bone metabolism indicators and bone density were significantly improved.

Buchwald-Hartwig Amination of Coordinating Heterocycles Enabled by Large-but-Flexible Pd-BIAN-NHC Catalysts.

A new class of large-but-flexible Pd-BIAN-NHC catalysts (BIAN=acenaphthoimidazolylidene, NHC=N-heterocyclic carbene) has been rationally designed to enable the challenging Buchwald-Hartwig amination of coordinating heterocycles. This robust class of BIAN-NHC catalysts permits cross-coupling under practical aerobic conditions of a variety of heterocycles with aryl, alkyl, and heteroarylamines, including historically challenging oxazoles and thiazoles as well as electron-deficient heterocycles containing multiple heteroatoms with BIAN-INon (N,N'-bis(2,6-di(4-heptyl)phenyl)-7H-acenaphtho[1,2-d]imidazol-8-ylidene) as the most effective ligand. Studies on the ligand structure and electronic properties of the carbene center are reported. The study should facilitate the discovery of even more active catalyst systems based on the unique BIAN-NHC scaffold.

SIRT3 (Sirtuin-3) Prevents Ang II (Angiotensin II)-Induced Macrophage Metabolic Switch Improving Perivascular Adipose Tissue Function.

OBJECTIVE: Infiltrated macrophages actively promote perivascular adipose tissue remodeling and represent a dominant population in the perivascular adipose tissue microenvironment of hypertensive mice. However, the role of macrophages in initiating metabolic inflammation remains uncertain. SIRT3 (sirtuin-3), a NAD-dependent deacetylase, is sensitive to metabolic status and mediates adaptation responses. In this study, we investigated the role of SIRT3-mediated metabolic shift in regulating NLRP3 (Nod-like receptor family pyrin domain-containing 3) inflammasome activation. Approach and Results: Here, we report that Ang II (angiotensin II) accelerates perivascular adipose tissue inflammation and fibrosis, accompanied by NLRP3 inflammasome activation and IL (interleukin)-1ß secretion in myeloid SIRT3 knockout (SIRT3-/-) mice. This effect is associated with adipose tissue mitochondrial dysfunction. In vitro studies indicate that the deletion of SIRT3 in bone marrow-derived macrophages induces IL-1ß production by shifting the metabolic phenotype from oxidative phosphorylation to glycolysis. Mechanistically, SIRT3 deacetylates and activates PDHA1 (pyruvate dehydrogenase E1 alpha) at lysine 83, and the loss of SIRT3 leads to PDH activity decrease and lactate accumulation. Knocking down LDHA (lactate dehydrogenase A) or using carnosine, a buffer against lactic acid, attenuates IL-1ß secretion. Furthermore, the blockade of IL-1ß from macrophages into brown adipocytes restores thermogenic markers and mitochondrial oxygen consumption. Moreover, NLRP3 knockout (NLRP3-/-) mice exhibited reduced IL-1ß production while rescuing the mitochondrial function of brown adipocytes and alleviating perivascular adipose tissue fibrosis. CONCLUSIONS: SIRT3 represents a potential therapeutic target to attenuate NLRP3-related inflammation. Pharmacological targeting of glycolytic metabolism may represent an effective therapeutic approach.

Charge-Storage Nickel Substrate-Boosted CuP2 Nanosheet for the Electrochemical Oxygen Evolution Reaction.

The electrochemical oxygen evolution reaction (OER) is an essential anodic reaction that converts sustainable energy into chemical fuels, as it can provide protons and electrons. One of the most challenging research directions for the practical application of the OER is the elevation of the activity of noble-metal-free electrocatalysts. Here, we report that the nickel foam can be used as an electron-deficient substrate to tune the surface oxidation state of catalytic electrodes and thus boost the OER activity of CuP2 nanosheets via a charge-storage mechanism. The as-obtained self-standing CuP2/Ni electrodes delivered a current density of 220 mA cm-2 at 370 mV overpotential, which is approximately 5.5 times higher than the benchmarked IrO2 on nickel foam. This work sheds some new light on the design of low-cost electrocatalysts or electrodes with high activity for the electrochemical OER.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

Fate of endosulfan in ginseng farm and effect of granular biochar treatment on endosulfan accumulation in ginseng.

Endosulfan was widely used as an insecticide in the agricultural sector before its environmental persistence was fully understood. Although its fate and transport in the environment have been studied, the effects of historic endosulfan residues in soil and its bioaccumulation in crops are not well understood. This knowledge gap was addressed by investigating the dissipation and bioaccumulation of endosulfan in ginseng as a perennial crop in fresh and aged endosulfan-contaminated fields. In addition, the effect of granular biochar (GBC) treatment on the bioaccumulation factor (BAF) of endosulfan residue in ginseng was assessed. The 50% dissipation time (DT50) of the total endosulfan was over 770 days in both the fresh and aged soils under mulching conditions. This was at least twofold greater than the reported (6- > 200 days) in arable soil. Among the endosulfan congeners, the main contributor to the soil residue was endosulfan sulfate, as observed from 150 days after treatment. The BAF for the 2-year-old ginseng was similar in the fresh (1.682-2.055) and aged (1.372-2.570) soils, whereas the BAF for the 3-year-old ginseng in the aged soil (1.087-1.137) was lower than that in the fresh soil (1.771-2.387). The treatment with 0.3 wt% GBC extended the DT50 of endosulfan in soil; however, this could successfully suppress endosulfan uptake, and reduced the BAFs by 66.5-67.7% in the freshly contaminated soil and 32.3-41.4% in the aged soil. Thus, this adsorbent treatment could be an effective, financially viable, and sustainable option to protect human health by reducing plant uptake of endosulfan from contaminated soils.

[Analysis of the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt].

Objective: To explore the necessity of anticoagulation therapy and influencing factors of stent occlusion after transjugular intrahepatic portosystemic shunt. Methods: The basic information, laboratory test results, preoperative portal venous pressure, postoperative anticoagulation time, postoperative stent stenosis or occlusion, followed-up and other data of all patients who underwent TIPS surgery in Shandong Provincial Hospital from 2010 to 2019 were retrospectively analyzed. Data were analyzed using t-test, χ2 test, and multivariate analysis (logistic regression and Cox-regression-analysis). Results: A total of 280 cases were finally included in the study, of which 110 (39.3%) had stent stenosis or occlusion, and 170 (60.7%) had stent patency. New or worsening ascites were identified in 194 cases during the follow-up period, including 14 (31.1%) cases in the stent stenosis or occlusion group and 19 (12.8%) cases in the stent patency group. Univariate analysis showed that presence or absence of platelet (P=0.037) and total bilirubin (P=0.038) were correlated with stent stenosis or occlusion. Postoperative continuous anticoagulation was correlated with stent blockage (P=0.029) in patients with partial portal vein thrombosis. Postoperative continuous anticoagulation and stent occlusions were not significantly correlated in patients with preoperative portal cavernoma and preoperative portal vein patency (P=0.848; P=0.744). Multivariate analysis results showed that whether long-term anticoagulation (P=0.017), all-cause rebleeding (P<0.001), postoperative significant hepatic encephalopathy (P<0.012), and postoperative new or worsening ascites (P<0.001) was significantly associated with stent occlusion (P<0.05), while platelets (P=0.134), total bilirubin (P=0.229), international normalized ratio (P=0.436), and portal vein pressure (P=0.230) were not significantly associated with stent occlusion after surgery. Conclusion: In patients with partial portal vein thrombosis before surgery, continuous anticoagulation for 30 days post-TIPS therapy can effectively prevent stent stenosis or occlusion; while in patients with portal vein patency, portal cavernoma and complete portal vein blockage before surgery, postoperative anticoagulation has no significant effect on stent stenosis or occlusion.

The association of metabolic health obesity with incidence of carotid artery plaque in Chinese adults.

BACKGROUND AND AIMS: We aimed to evaluate the association between different obese phenotypes with carotid artery plaque (CAP) event. METHOD AND RESULTS: The current retrospective cohort study was performed in 32,778 Chinese adults (19,221 men and 13,557 women, aged 41.9 ± 11.0 years). Obese phenotypes were assessed based on baseline body mass index (<24.0 vs. ≥24.0 kg/m2) and metabolic characteristics (health vs. unhealth). All the participants were further classified into four groups: metabolic health and normal weight (MHNW), metabolic unhealth and normal weight (MUHNW), metabolic health and overweight (MHO), and metabolic unhealth and overweight (MUHO). Ultrasound B-mode imaging was annually performed to evaluate CAP throughout the study. We have identified 2142 CAP cases during 5-year follow-up. Comparing with the MHNW group, the hazard ratios for the risk of incident CAP was 2.44 (95% CI:1.92 and 3.09) for the MUHNW group, 1.52 (95% CI:1.06 and 2.18) for the MHO group, and 1.8 (95% CI:1.4 and 2.33) for the MUHO group. The association was more pronounced in young adults (<65 y) than that in aged adults (≥65 y). Sensitivity analysis generated similar results with the main analysis. CONCLUSION: MUHNW, MHO, and MUHO were associated with the risk of CAP.

Safety and efficacy of common vitamin D supplementation in primary hyperparathyroidism and coexistent vitamin D deficiency and insufficiency: a systematic review and meta-analysis.

PURPOSE: Primary hyperparathyroidism (PHPT) is characterized by excessive secretion of parathyroid hormone (PTH). Vitamin D deficiency can stimulate parathyroid secretion. However, whether to correct vitamin D deficiency in patients with PHPT is controversial. We aimed to evaluate the safety and efficacy of vitamin D replacement in patients with PHPT. METHODS: We searched PubMed, Cochrane Library, and Embase. The relevant data were extracted from the included documents. The methodological items for non-randomized studies score entries were used for evaluation of quality. Review Manager 5.3 and Stata 12.0 were used for statistical analysis. RESULTS: A total of 11 articles were included with a total of 388 patients. The serum calcium mean difference (MD) was - 0.06 mg/dL [95% confidence interval (95% CI) - 0.16, 0.04]. Subgroup analysis showed that serum calcium levels did not change if the intervention time exceeded 1 month. The 24-h urinary calcium MD was 36.78 mg/day (95% CI - 37.15, 110.71), which indicated that there was no significant effect of vitamin D supplementation on 24-h urinary calcium levels. The MD of PTH was - 16.01 pg/mL (95% CI - 28.79, - 3.24). Subgroup analysis according to the intervention time showed that vitamin D intervention for more than 1 month significantly reduced PTH levels. The ALP MD was - 10.81 U/L (95% CI - 13.98, - 7.63), which indicated Vitamin D supplementation reduced its level. The MD of 25-hydroxyvitamin D was 22.09 µg/L (95% CI 15.01, 29.17), and no source of heterogeneity was found. CONCLUSION: Vitamin D supplementation in patients with PHPT and vitamin D deficiency significantly reduces PTH and ALP levels without causing hypercalcemia and hypercalciuria.

[Quantitative hepatitis B core antibody levels can be used as a predictive index of HBsAg clearance].

Objective: To explore the possibility of hepatitis B core antibody (anti-HBc) in predicting hepatitis B virus surface antigen (HBsAg) clearance. Methods: Sixty cases with chronic hepatitis B who were previously treated with peginterferon α-2a combined with nucleos(t)ide analogues (NAs) antiviral therapy were divided according to the HBsAg clearance or non-clearance; 41 cases in the clearance group and 19 cases in the non-clearance group. Double antigen sandwich method was used to detect patients anti-HBc quantitative levels during the course of treatment and at baseline, 24, 48, 72 and 96 weeks. Logistic regression analysis and receiver operating characteristic curve (ROC) were used to evaluate the predictive ability of related influencing factors for HBsAg clearance. Results: With antiviral treatment prolongation, anti-HBC quantitative levels in the overall population showed a progressive downward trend in the clearance group and the non-clearance group, but the anti-HBC level in the clearance group was significantly higher than non-clearance group at the baseline and successive detection time points during the antiviral treatment (P < 0.05). Multivariate logistic regression showed that baseline quantitative anti-HBC level, HBsAg decline at week 24 (log10 IU / ml), and alanine aminotransferase (ALT) > 1.5 times the upper limit of normal value (ULN) were all influencing factors for HBsAg clearance during the treatment (OR = 0.156, P = 0.026; OR = 0.134, P = 0.023; OR = 0.239, P = 0.028). Among them, the baseline quantitative anti-HBc level was the best independent predictor for HBsAg clearance (OR = 0.235; P = 0.004), and the sensitivity and specificity for predicting HBsAg clearance at > 3.40 log10 IU/ mL were 56.1% and 89.5%, respectively. Logistic regression model was used as a reference to construct combined predictors in order to improve the prediction accuracy. Among them, the combined factor 3 had the highest predictive value (the area under the ROC curve had reached up to 0.870; 95%CI was 0.781 ~ 0.960; P < 0.001). The cut-off value of combined factor 3 was > 0.386, and the sensitivity and specificity were 80.5% and 78.9%, respectively. In addition, the combined index had further improved the predictive value, which is the combination of any two or more indexes based on the baseline quantitative anti-HBC level, and HBsAg clearance predictive rate had reached 94.12% ~ 100%. Conclusion: The baseline quantitative anti-HBC level has the highest predictive value for HBsAg clearance. The combination of ALT > 1.5×ULN and HBsAg decline at 24 weeks during the treatment can more precisely predict HBsAg clearance. Therefore, it is a reliable non-invasive biomarker.

"Bulky-Yet-Flexible" α-Diimine Palladium-Catalyzed Reductive Heck Cross-Coupling: Highly Anti-Markovnikov-Selective Hydroarylation of Alkene in Air.

To pursue a highly regioselective and efficient reductive Heck reaction, a series of moisture- and air-stable α-diimine palladium precatalysts were rationally designed, readily synthesized, and fully characterized. The relationship between the structures of the palladium complexes and the catalytic properties was investigated. It was revealed that the"bulky-yet-flexible"palladium complexes allowed highly anti-Markovnikov-selective hydroarylation of alkenes with (hetero)aryl bromides under aerobic conditions. Further synthetic application of the present protocol could provide rapid and straightforward access to functional and biologically active molecules.

Muscle synergy for upper limb damping behavior during object transport while walking in healthy young individuals.

Transporting an object during locomotion is one of the most common activities humans perform. Previous studies have shown that continuous and predictive control of grip force, along with the inertial load force of the object, is required to complete this task successfully. Another possible CNS strategy to ensure the dynamic stability of the upper limb is to modify the apparent stiffness and damping via altered muscle activation patterns. In this study, the term damping was used to describe a reduction in upper limb vertical oscillation amplitude to maintain the orientation of the hand-held object. The goal of this study was to identify the neuromuscular strategy for controlling the upper limb during object transport while walking. Three-dimensional kinematic and surface electromyography (EMG) data were recorded from eight, right-handed, healthy young adults who were instructed to walk on a treadmill while carrying an object in their dominant/non-dominant hand, with dominant/non-dominant arm positioning but without an object, and without any object or instructed arm-positioning. EMG recordings from the dominant and non-dominant arms were decomposed separately into underlying muscle synergies using non-negative matrix factorization (NNMF). Results revealed that the dominant arm showed higher damping compared to the non-dominant arm. All muscles showed higher mean levels of activation during object transport except for posterior deltoid (PD), with activation peaks occurring around or slightly before heel contact. The muscle synergy analysis revealed an anticipatory stabilization of the shoulder and elbow joints through a proximal-to-distal muscle activation pattern. These activations appear to play an essential role in maintaining the stability of the carried object in addition to the adjustment of grip force against the perturbations caused by heel contact during walking.

Lactococcus lactis harbouring Ara h 2.02 alleviates allergen-specific Th2-associated responses in sensitized mice.

AIM: To study the prophylactic effect of recombinant Lactococcus lactis (rLl) harbouring Ara h 2.02 peanut allergen, in sensitized and challenged mice. METHODS AND RESULTS: Ara h 2.02 cDNA was cloned into pNZ8048 for heterologous expression in L. lactis. The purified recombinant allergen showed IgE binding comparable with native Ara h 2. Balb/c mice were fed with either recombinant (rLl), nonrecombinant L. lactis (Ll) or NaHCO3 (Sham) prior to sensitization and challenged with rAra h 2.02, whereas the baseline group was only fed with Ll. Allergen-specific immunoglobulin and splenocyte cytokines responses were determined for each mouse. Mice fed with either Ll or rLl showed significant alleviation of IgE and IgG1 compared to the Sham group. Despite no significant decrease in Th2 (IL-4, IL-13, IL-6) or increase in Th1 (IFN-γ) cytokines, both groups showed lower IL-10 level, while the IL-4 : IFN-γ ratio was significantly lower for rLl compared to Ll group. CONCLUSIONS: Oral administration of rLl harbouring Ara h 2.02 demonstrated alleviation of Th2-associated responses in allergen-challenged mice and a possible added allergen-specific prophylactic effect. SIGNIFICANCE AND IMPACT OF THE STUDY: Ara h 2.02 coupled with the intrinsic properties of probiotic L. lactis as a delivery vehicle can be explored for the development of a commercially scalable vaccine.

[Diagnostic value of 4-dimensional computed tomography in preoperative localization in patients with primary hyperparathyroidism].

Objective: To provide more options for preoperative localization diagnosis in patients with primary hyperparathyroidism (PHPT), the diagnostic efficacy of parathyroid 4-dimensional computed tomography (4D-CT) in patients with PHPT was evaluated. Methods: This was a single-center retrospective study including 57 patients with surgical proved PHPT. All of the patients underwent 4D-CT, 99Tcm -sestamibi parathyroid imaging (MIBI), and ultrasonography (US) preoperatively. The reference standard for correct localization was based on operation reports and pathology confirmation. The patients were grouped according to the preoperative serum calcium levels, tumor diameter, or ectopic lesions (yes/no), respectively. The sensitivity, specificity, positive predictive value, negative predictive value and area under the curve (AUC) of 4D-CT, MIBI and US, alone or in combination, were analyzed in total and each subgroup patients. Results: Fifty-seven patients (39 women, 18 men; mean age of 56.5 years) were evaluated, including four cases with multi-gland disease and thirteen cases with ectopic parathyroid lesions. In all the patients, similar diagnostic efficacy was found in 4D-CT (AUC: 0.943) and MIBI (AUC: 0.927), both of which were higher than that of US (AUC: 0.847) (P = 0.01 for 4D-CT vs. US; P = 0.04 for MIBI vs. US). In a subset analysis for ectopic quadrants, the diagnostic efficacy of 4D-CT was significantly higher than that of MIBI (P = 0.04) or US (P = 0.01), with the sensitivity of 100%, 69.2%, and 61.5%, and AUC of 0.989, 0.846, and 0.808 for 4D-CT, MIBI and US, respectively. Conclusions: 4D-CT has similar diagnostic efficacy for preoperative localization to MIBI in patients with PHPT, and it is superior to MIBI and US in identifying the ectopic parathyroid gland. 4D-CT can be recommended as an alternative preoperative localization method, especially when parathyroid lesions could not be precisely located by US and MIBI.