Burning plasma achieved in inertial fusion.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

[Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 µg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

[Analysis of the effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture].

Objective: To examine the feasibility and clinical effect of all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture. Methods: This is a retrospective case series study. From February 2021 to February 2023, the clinical data of 24 patients (30 feet) with Achilles tendon contracture treated with all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening were analyzed retrospectively. There were 10 males and 14 females, aged (32.8±16.1) years (range: 9 to 62 years). There were 8 cases of left side only, 10 cases of right side only and 6 cases of bilateral. There were 14 cases (16 feet) of foot varus, 4 cases (6 feet) of foot valgus, and 6 cases (8 feet) without deformity. All patients underwent all-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening. The surgical effects were evaluated using the maximum dorsal extension angle of ankle joint in knee extension position, the visual analogue scale (VAS) of pain, the American Orthopedic Foot and Ankle Society ankle-hindfoot score(AOFAS-AH). Paired sample t test was used to compare the scores before and after operation. Results: All patients successfully completed the operation, and the operation time of Achilles tendon lengthening was (22.0±5.7)minutes (range: 15 to 35 minutes) and the intraoperative blood loss was (6.5±2.7)ml (range: 2 to 15 ml). All patients primarily healing without any complications such as sural nerve injury, Achilles tendon rupture, important blood vessel injury, and obvious decrease of lift heel strength of achilles tendon. All 24 patients were followed up for (17.2±4.5) months (range: 12 to 28 months). One patient suffered from lift heel's weakness in one foot after operation, and recovered after repeated lift heel functional exercises. The ankle dorsiflexion function of two patients with calf triceps spasm were not improved after operation, and it was obviously improved after botulinum toxin injection. At the last follow-up, the maximum dorsal extension angle of ankle joint in knee extension position increased from -9.2°±7.6°(range:-25° to 5°) preoperatively to 14.5°±7.0°(range:0° to 28°)(t=24.83, P<0.01); the VAS score was reduced from (4.5±1.7) points (range:1 to 8 points) preoperatively to (1.5±0.9) points (range:0 to 3 points) (t=9.53, P<0.01), the AOFAS-AH was increased from (60.5±11.4)points (range:38 to 85 points) to (90.8±5.4) points (range:80-100 points)(t=14.21, P<0.01). Conclusions: All-inside endoscopic procedure through two portals combined with double-hemisection Achilles tendon lengthening for Achilles tendon contracture not only provides Achilles tendon lengthening, but also avoids complications such as Achilles tendon rupture and sural nerve injury. It is an effective method for the treatment of Achilles tendon contracture.

[Machine learning: a new direction for assisting the application of deep brain stimulation].

In recent years, deep brain stimulation has been widely used in the treatment of various difficult diseases of the nervous system. The rapid development of machine learning algorithms has greatly promoted the application and development of deep brain stimulation. Machine learning can help in preoperative screening of surgical candidates, outcome prediction and surgical planning. It can assist target localization during operation. More importantly, the local field potential signals recorded by macroscopic electrodes can be analyzed in real time after surgery, which provides a basis for the development of a closed-loop stimulation system. Of course, the application of machine learning also has its limitations and challenges, such as dimensionality reduction of high-dimensional data, development and validation of new models and etc, which need to be further explored and improved.

[Early brain imaging changes and its influence on electrode impedance after implantation of 3.0 T MRI-compatible deep brain stimulation system in Parkinson's disease subthalamic nucleus].

Objective: To analyze the imaging changes of in the early period after subthalamic nucleus (STN) deep brain stimulation (DBS) surgery for Parkinson's disease (PD) and its impact on electrode impedance by the application of 3.0T MRI-compatible devices. Methods: A retrospective analysis was performed for the data of 43 PD patients who underwent 3.0T MRI-compatible STN-DBS surgery from October 2022 to April 2023 at the First Affiliated Hospital of USTC(Anhui Provincial Hospital), including 27 males and 16 females, aged 43-68 (56±5) years. All patients underwent postoperative 3.0T MRI, CT scans,and impedance measurements 1 week postoperatively.Fifteen patients underwent 3.0T MRI and impedance measurements 1 month postoperatively. The differences in impedance of electrode contacts before and after the 3.0T MRI scans were compared. The occurrence of peri-lead cerebral edema (PLE) in patients was analyzed, as well as the differences in PLE detection rates between the two imaging methods, and the differences in the incidence and volume of PLE at different microelectrode recordings, the occurrence and detection of postoperative PLE, and different microelectrode recording (MER) times and different time nodes were compared. The correlation between electrode impedance and the volume of edema around the nucleus was analyzed. Results: All 43 patients successfully underwent surgery, with a total of 86 electrodes implanted. There was no significant difference in electrode impedance values before and after the 3.0T MRI examinations at 1 week and 1 month postoperatively. The PLE detection rate with 3.0T MRI was 95.12%(39/43), which is significantly higher than that of CT imaging 17.07% (7/43)(χ2=50.705, P<0.001). One week after surgery, the incidence and volume of PLE were higher in the multiple MER group compared with the single MER group, but the difference was not statistically significant. The volume of PLE [M(Q1, Q3) 0 (0, 1.211) cm3] at 1 month was significantly smaller than that at 1 week [0.243 (0, 2.914) cm3] (Z=-3.408, P=0.001). The impedance of electrode contacts within 1 month postoperatively showed a trend of initial decrease followed by an increase, which was negatively correlated with SE volume(r=-0.317, P=0.014). Conclusions: The application of 3.0T MRI-compatible DBS devices in the surgical treatment of PD patients improves the accuracy of early postoperative imaging assessment. The electrode impedance is more stable as the edema around the nucleus subsided at 1 month after surgery, which is suitable for the first program control.

[Posterior arthroscopic subtalar arthrodesis for symptomatic adult talocalcaneal coalition].

Objective: To investigate the functional outcomes of posterior arthroscopic subtalar arthrodesis (PASTA) for adult patients presenting with symptomatic talocalcaneal coalition. Methods: The study was a retrospective case-series research.The data of 17 adult patients (17 feet) with symptomatic talocalcaneal coalitions,treated with PASTA from March 2018 to February 2022 in Xuzhou Central Hospital were collected.This procedure involved 10 males and 7 females,aged (42.4±7.5) years(range:31 to 58 years).There were 9 cases on the right side and 7 cases on the left side.According to the Rozansky classification,there were 4 cases of type Ⅰ,7 cases of type Ⅱ, 3 cases of type Ⅲ,3 cases of type Ⅳ.The following items such as wound healing and bony union of the subtalar joint were observed.Clinical assessment was performed using pain visual analogue scale (VAS),American Orthopaedic Foot & Ankle Society (AOFAS) ankle-hindfoot scores and 36-item short form health survey (SF-36) scores.The paired t test was used for data comparison. Results: The follow-up time was (24.8±6.9) months(range:12 to 40 months).There were no complications such as wound infection,deep vein thrombosis,nonunion,or screw breakage.One patient with preoperative spasm,relieved after the second surgical procedure (peroneal brevis tendon lengthening).The union time of the subtalar joint was (8.8±2.2) weeks(range:6 to 12 weeks).At the final follow-up,the VAS decreased from (6.4±1.3) to (1.3±0.9)(t=14.114,P<0.01), the AOFAS ankle-hindfoot score increased from (49.0±8.1) to (90.0±5.1)(t=38.782,P<0.01),and the SF-36 score increased from (50.8±9.5) to (91.0±4.9)(t=20.468,P<0.01). Conclusion: PASTA for adult patients presenting with symptomatic talocalcaneal coalition offers advantages of minimal trauma,fast recovery,and few complications,which is an effective method.

[Arthroscopic treatment of acute closed noninsertional rupture of Achilles tendon].

Objective: To investigate the clinical efficacy of arthroscopic treatment of acute closed noninsertional rupture of Achilles tendon. Methods: The clinical and imaging data of 30 patients (30 feet) with acute closed noninsertional rupture of Achilles tendon who were treated with all-inside arthroscopic technique at the Department of Hand and Foot Microsurgery,Xuzhou Central Hospital from June 2018 to June 2020 were analyzed retrospectively. There were 26 males and 4 females,aged (38.3±8.5)years old(range:19 to 66 years). There were 22 cases on the right side and 8 cases on the left side. The duration from injury to surgery was (2.1±1.4) days (range:1 to 7 days).All patients were treated with all-inside arthroscopic technique.The function of the ankle and the foot was assessed using visual analogue scale (VAS),the American Orthopaedic Foot & Ankle Society (AOFAS) ankle hindfoot scale and the Achilles tendon total rupture score (ATRS). The Arner-Lindholm score system was used to evaluate the excellent and good rate of clinical effect. Paired sample t test or rank-sum test was used for data comparison. Results: The patients were followed up for (18.6±2.2)months(range:12 to 28 months).All the wounds healed at the first stage.No complication such as infection,sural nerve injury or re-rupture happened.Two patinets felt mild pain after a long time exercise, and were alleviated by microwave therapy and stretching the Achilles tendon consistently.Another patient was unable to do a sustained single stance heel raise,which was recovered after repeated function practice.At the last follow-up,the VAS (M(IQR)) decreased from 6(5) preoperatively to 0(1)(Z=6.512,P<0.01),the AOFAS ankle hindfoot scale improved from 60.6±8.3 preoperatively to 96.3±4.8(t=-29.774,P<0.01),and the ATRS improved from 61.7±7.8 preoperatively to 97.1±2.3 (t=-53.661,P<0.01).According to the Arner-Lindholm score system,27 cases were excellent,3 cases were good,and the excellent and good rate was 100%. Conclusions: The all-inside arthroscopic technique not only ensures the quality of tendon ananstomosis,but also avoids injury to the sural nerve.It has the advantages of small trauma,faster recovery and fewer complications.

High urinary excretion rate of glucose attenuates serum uric acid level in type 2 diabetes with normal renal function.

AIMS/INTRODUCTION: The relationship between urinary excretion rate of glucose (UEGL) and uric acid (UA) metabolism in adults with type 2 diabetes (T2D) remains unclear to date. This study aimed to investigate the relationships of UEGL with serum UA (SUA), urinary excretion rate of uric acid (UEUA), and renal clearance of uric acid (CLUA) in adults with T2D. We hypothesised that high UEGL increases UA excretion, which in turn leads to lower SUA. MATERIALS AND METHODS: This was a cross-sectional study of 635 inpatients with T2D recruited between 2018 and 2019. The relationships of UEGL with UEUA, CLUA, and hyperuricaemia were assessed using analysis of covariance and multivariate regression analysis. RESULTS: Patients in the higher quartile of UEGL tended to have lower SUA levels than those in the lower quartile. In contrast, patients in the higher quartile of UEGL tended to have higher CLUA (p for trend < 0.0001), and a similar trend was observed for UEUA. In adjusted multivariable linear regression model, UEGL was negatively correlated with SUA (ß = - 0.023, 95% CI - 0.034 to - 0.013, p < 0.0001). However, positive correlations of UEGL with UEUA (ß = 0.046, 95% CI 0.018-0.074, p = 0.001) and CLUA (ß = 0.063, 95% CI 0.042-0.085, p < 0.0001) were found. Furthermore, consistent significant inverse associations were observed between quartiles of UEGL and hyperuricaemia in the adjusted multivariate logistic regression model. CONCLUSIONS: A high UEGL level was positively correlated with UEUA and CLUA. Moreover, it was inversely associated with SUA level, and a consistently increased UEGL level reduced the risk of hyperuricaemia in patients with T2D.

[Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma: a clinicopathological study].

Objective: To investigate the clinicopathological features, immunohistochemical characteristics, differential diagnosis and prognosis of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinomas. Methods: Two cases of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma were collected at Fudan University Shanghai Cancer Center, Shanghai, China from 2017 to 2018. The clinicopathological characteristics were analyzed. Hematoxylin and eosin, and immunohistochemical stains were performed, and the relevant literatures were reviewed. Results: The two patients were both male, aged 60 and 74 years, respectively. Their symptoms were both abdominal pain. The tumor arose in the esophagogastric junction in case 1, and the cardia to the fundus and the posterior wall of the upper part of gastric body in case 2. Both tumors were present as an ulcerative mass. The patients died of tumor 11 months and 8 months after surgery, respectively. Histologically, the tumor cells arranged in sheets, nests, cords or trabecular patterns, and pseudoavleolar structure. The tumor cells were epithelioid with uniform morphology, while the tumors showed scant stroma and massive necrosis. Variable rhabdoid cells and multinucleated giant cells were seen in both cases. SMARCA4 encoding protein BRG1 was undetectable in both tumors, while SMARCB1 encoding protein INI1 was detected. The tumor cells were diffusely positive for vimentin and negative for epithelial marker (CKpan), gastrointestinal stromal tumor markers (CD117 and DOG1), myogenic markers (desmin and myogenin), melanoma markers (S-100 protein, SOX10 and HMB45), and lymphohematopoietic markers (LCA and CD20). Conclusions: Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma is a rare and highly aggressive tumor with poor prognosis. The detection of subunits protein expression of SWI/SNF complex is important for diagnosis of the tumor.

Efficacy and safety of evogliptin treatment in patients with type 2 diabetes: A multicentre, active-controlled, randomized, double-blind study with open-label extension (the EVERGREEN study).

AIM: To investigate the efficacy and safety of evogliptin compared with linagliptin in patients with type 2 diabetes. MATERIALS AND METHODS: In this 12-week, multicentre, randomized, double-blind, active-controlled, and 12-week open-label extension study, a total of 207 patients with type 2 diabetes who had HbA1c levels of 7.0%-10.0% were randomized 1:1 to receive evogliptin 5 mg (n = 102) or linagliptin 5 mg (n = 105) daily for 12 weeks. The primary efficacy endpoint was the change from baseline HbA1c at week 12. The secondary endpoint was the change in the mean amplitude of glycaemic excursion (MAGE) assessed by continuous glucose monitoring. In the extension study conducted during the following 12 weeks, evogliptin 5 mg daily was administered to both groups: evogliptin/evogliptin group (n = 95) and linagliptin/evogliptin group (n = 92). RESULTS: After 12 weeks of treatment, the mean change in HbA1c in the evogliptin group and in the linagliptin group was -0.85% and -0.75%, respectively. The between-group difference was -0.10% (95% CI: -0.32 to 0.11), showing non-inferiority based on a non-inferiority margin of 0.4%. The change in MAGE was -24.6 mg/dL in the evogliptin group and -16.7 mg/dL in the linagliptin group. These values were significantly lower than the baseline values in both groups. However, they did not differ significantly between the two groups. In the evogliptin/evogliptin group at week 24, HbA1c decreased by -0.94%, with HbA1c values of <7.0% in 80.2% of the patients. The incidence and types of adverse events were comparable between the two groups for 24 weeks. CONCLUSION: In this study, the glucose-lowering efficacy of evogliptin was non-inferior to linagliptin. It was maintained at week 24 with a 0.94% reduction in HbA1c. Evogliptin therapy improved glycaemic variability without causing any serious adverse events in patients with type 2 diabetes.

[Arthroscopy-assisted percutaneous reduction and screw fixation for displaced intra-articular calcaneal fractures].

Objective: To investigate the surgical technology and clinical efficacy of using the all-inside arthroscopic treatment of intra-articular displaced calcaneal fracture. Methods: A retrospective analysis was made of 46 patients (46 feet) with intra-articular displaced calcaneal fractures treated by modified all-inside arthroscopic from December 2015 to December 2017 in Xuzhou Central Hospital. Twenty-eight cases (28 feet) were male and 18 cases (18 feet) were female, aged from 19 to 60 years (mean (39±13) years). The time from injury to operation was 1 to 10 days (mean (4.5±2.2) days). The pre-operative visual analogue scale (VAS) of pain ranged from 4 to 8 points, mean (6.3±1.8) points. No other combined injuries were found in the affected feet in all patients. All patients were treated with anterolateral, lateral and posterolateral approaches of arthroscopically assisted reduction for calcaneal fractures, and fixed with hollow screw. Main outcome measures included the pain, foot appearance, and the scores of the American Orthopedic Foot & Ankle Society (AOFAS) Scale and the Maryland Scale. Paired t test was used when the data before and after the operation were compared. Results: All incisions healed in one stage without postoperative complications such as nerve, vessel and tendon injury. The mean follow-up period ranged from 12 to 36 months, mean (21±9) months. Postoperatively X-ray showed complete fracture healing time was 8 to 12 weeks, mean (10.4±2.3) weeks. At the last follow-up, the ankle and talocalcaneal joints movement and appearance were ideal, and no traumatic arthritis was found. The VAS score of talocalcaneal joint was 0. AOFAS score increased from 58±13 to 96±9 and Maryland score increased from 72±11 to 98±8 after the operation, the differences were all significant (t=15.958, 12.496, both P<0.05). Conclusion: The all-inside arthroscopic treatment of the intra-articular displaced calcaneal fracture is an effective and precise method, with accurately outcomes, precise reduction and minimally postoperative complications.

[Ovarian Sertoli-Leydig cell tumors: DICER1 hotspot mutations and associated clinicopathological features].

Objective: To investigate DICER1 hotspot mutations in ovarian Sertoli-Leydig cell tumor (SLCT) and its associated clinicopathological features. Methods: Forty-three SLCTs and 40 other sex cord-stromal tumors (SCSTs) diagnosed between 2010 and 2017 at Fudan University Shanghai Cancer Center were examined for somatic DICER1 hotspot mutations by Sanger sequencing. The associations between mutation status and clinicopathological features, including patient age, tumor differentiation and recurrence, were analyzed. Results: Somatic DICER1 mutations were found in 51% (22/43) of SLCTs, while none in the other 40 SCSTs. The most common mutation of DICER1 was p.D1709N in exon 24 (41%, 9/22) and the second most common mutation of DICER1 was p.E1813K in exon 25 (14%, 3/22). A novel frameshift mutation (c.5464delG, p.M1837fs*16) was identified in one SLCT with microcystic pattern. Mutations were more likely to occur in patients under forty years of age (P=0.046), whereas no significant associations were found between DICER1 mutations and clinical symptoms, morphology or tumor recurrence. Conclusions: Somatic DCIER1 hotspot mutations are specifically found in SLCT and may serve as an ancillary marker in differential diagnosis of SLCT from other SCST. The mutations occur more often in young patients (<40 years old). Additional studies are warranted to examine the associations between DICER1 mutations and clinicopathological features and prognosis of SLCT.

[The reconstruction of Myerson type â ¢ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft].

Objective: To evaluate the clinical outcome of the reconstruction of Myerson type Ⅲ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft. Methods: Clinical data of 32 patients(32 ankles) with Myerson type Ⅲ chronic Achilles tendon rupture who were treated by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft at Department of Hand and Foot Microsurgery, Xuzhou Central Hospital from September 2013 to September 2018 were analyzed retrospectively.There were 28 males and 4 females, aged 45.5 years old(range: 22 to 69 years old), 12 cases in the right side and 20 in the left.All patients were treated by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft for Myerson type Ⅲ chronic Achilles tendon rupture reconstruction.The functional recovery of the ankle was evaluated according to ankle-hindfood score of American Orthopaedic Foot and Ankle Society (AOFAS) Ankle Hindfoot Scale, Achilles tendon total rupture score (ATRS), visual analogue scale (VAS).Arner-Lindholm score was used to evaluate the excellent and good rate.The quantitative data were compared using t-test or Wilcoxon test. Results: The 32 patients were followed up for 33 months (range: 15 to 72 months).No serious postoperative complications such as infection, sural nerve injury or tend re-rupture outcomes were reported.Three patients complained of mild pain when after a minimum sitting, walking or jogging, which were completely relieved by simple physical therapy or continuous stretching of Achilles tendon.At the last follow-up, the VAS decreased from 3 (5) (M (Q(R)) ) preoperative to 0 (3) (Z=1.357, P<0.01) and AOFAS ankle hindfoot scale improved from 58.6±13.5 preoperative to 95.5±4.0 (t=16.9, P=0.00), ATRS improved from 47.5±9.3 preoperative to 96.6±3.3 (t=25.661, P<0.01).According to the score of Arner-Lindholm, 20 cases were excellent, 12 cases were good, and the excellent and good rate was 100%. Conclusion: The reconstruction of Myerson type Ⅲ chronic Achilles tendon rupture by using the total arthroscopic technique combined with free semitendinosus tendon and gracilis tendon autograft has the advantages of safety, reliability, effectiveness and minor injury.

Associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage enzymes in patients with knee osteoarthritis.

OBJECTIVE: Animal studies suggest that S100A8/S100A9 may be involved in the pathogenesis of osteoarthritis (OA); however, there has been no clinical study examining the associations between serum S100A8/S100A9 and knee symptoms, joint structures and cartilage degradation enzymes in knee OA patients so far. Therefore, this study was designed to investigate the cross-sectional associations between serum levels of S100A8/S100A9 and the outcomes in patients with knee OA. DESIGN: A total of 141 subjects with clinical knee OA were included. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score was used to assess joint symptoms. Magnetic resonance imaging (MRI) was used to measure knee structural abnormalities including cartilage defects. Knee radiography was used to assess joint space narrowing (JSN), osteophytes and the radiographic severity of OA. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum levels of S100A8/S100A9, matrix metalloproteinase (MMP)-3, MMP10 and MMP13. RESULTS: In multivariable analyses, serum S100A8/S100A9 were positively associated with total WOMAC score (ß: 0.111 per 10 ng/ml, P = 0.021), WOMAC weight-bearing pain (ß: 0.015 per 10 ng/ml, P = 0.043) and WOMAC physical dysfunction (ß: 0.091 per 10 ng/ml, P = 0.010), and had positive associations with total cartilage defects and cartilage defects at lateral femoral, lateral tibial and medial femoral sites (ORs: 1.006-1.008 per 10 ng/ml, all P < 0.05) and serum levels of MMP3 (ß: 0.002 per 10 ng/ml, P = 0.032) in patients with clinical knee OA. CONCLUSIONS: Serum levels of S100A8/S100A9 were positively associated with increased knee symptoms, cartilage defects and serum cartilage degradation enzymes in patients with knee OA, suggesting that S100A8/S100A9 may have a role to play in knee OA. Future longitudinal studies are required to confirm these findings.

Detection of group B Streptococcus during antenatal screening in Western Australia: a comparison of culture and molecular methods.

AIM: Global screening strategies for Group B Streptococcus (GBS) include risk- or culture-based methods to guide intrapartum prophylaxis. In Western Australia (WA), antenatal culture-based screening is routine; however, numerous culture methods exist, in addition to molecular methods. We aimed to assess the comparability of research and diagnostic screening approaches. METHODS AND RESULTS: Vaginal and rectal swabs were self-collected by pregnant women (n = 531) from King Edward Memorial Hospital, WA, in parallel to routine screening (35-37 weeks of gestation). Research methods involved culture (Strep B Carrot Broth™ and StrepB CHROMagar™) and molecular methods (real-time PCR) and were compared to routine diagnostic screening (Lim Broth and Granada agar). Overall, GBS detection was comparable between research and diagnostic approaches (3-5% discrepancy, kappa = 0·76). Specificity/sensitivity of Carrot Broth™ was 100%/89%, while that of CHROMagar™ was 73%/100%, respectively. Direct PCR was unable to detect GBS in ~18% of specimens which were culture positive; however, it exhibited 100% specificity. CONCLUSIONS: This clinical evaluation of GBS screening methods provides support for current practice. SIGNIFICANCE AND IMPACT OF THE STUDY: Although CHROM was highly sensitive, further testing is recommended due to a high false-positive rate. Molecular assays are useful for rapid detection; however, low-titre samples may require additional enrichment prior to molecular analysis to improve sensitivity.

Nitrogen losses in anoxic marine sediments driven by Thioploca-anammox bacterial consortia.

Ninety per cent of marine organic matter burial occurs in continental margin sediments, where a substantial fraction of organic carbon escapes oxidation and enters long-term geologic storage within sedimentary rocks. In such environments, microbial metabolism is limited by the diffusive supply of electron acceptors. One strategy to optimize energy yields in a resource-limited habitat is symbiotic metabolite exchange among microbial associations. Thermodynamic and geochemical considerations indicate that microbial co-metabolisms are likely to play a critical part in sedimentary organic carbon cycling. Yet only one association, between methanotrophic archaea and sulphate-reducing bacteria, has been demonstrated in marine sediments in situ, and little is known of the role of microbial symbiotic interactions in other sedimentary biogeochemical cycles. Here we report in situ molecular and incubation-based evidence for a novel symbiotic consortium between two chemolithotrophic bacteria--anaerobic ammonium-oxidizing (anammox) bacteria and the nitrate-sequestering sulphur-oxidizing Thioploca species--in anoxic sediments of the Soledad basin at the Mexican Pacific margin. A mass balance of benthic solute fluxes and the corresponding nitrogen isotope composition of nitrate and ammonium fluxes indicate that anammox bacteria rely on Thioploca species for the supply of metabolic substrates and account for about 57 ± 21 per cent of the total benthic N2 production. We show that Thioploca-anammox symbiosis intensifies benthic fixed nitrogen losses in anoxic sediments, bypassing diffusion-imposed limitations by efficiently coupling the carbon, nitrogen and sulphur cycles.

In silico, in vitro and in vivo analysis of putative virulence factors identified in large clostridial toxin-negative, binary toxin- producing C. difficile strains.

The relevance of large clostridial toxin-negative, binary toxin-producing (A-B-CDT+) Clostridium difficile strains in human infection is still controversial. In this study, we investigated putative virulence traits that may contribute to the role of A-B-CDT+C. difficile strains in idiopathic diarrhea. Phenotypic assays were conducted on 148 strains of C. difficile comprising 10 different A-B-CDT+C. difficile ribotypes (RTs): 033, 238, 239, 288, 585, 586, QX143, QX444, QX521 and QX629. A subset of these isolates (n = 53) was whole-genome sequenced to identify genetic loci associated with virulence and survival. Motility studies showed that with the exception of RT 239 all RTs tested were non-motile. C. difficile RTs 033 and 288 had deletions in the F2 and F3 regions of their flagella operon while the F2 region was absent from strains of RTs 238, 585, 586, QX143, QX444, QX521 and QX629. The flagellin and flagella cap genes, fliC and fliD, respectively, involved in adherence and host colonization, were conserved in all strains, including reference strains. All A-B-CDT+C. difficile strains produced at least three extracellular enzymes (deoxyribonuclease, esterase and mucinase) indicating that these are important extracellular proteins. The toxicity of A-B-CDT+C. difficile strains in Vero cells was confirmed, however, pathogenicity was not demonstrated in a mouse model of disease. Despite successful colonization by most strains, there was no evidence of disease in mice. This study provides the first in-depth analysis of A-B-CDT+C. difficile strains and contributes to the current limited knowledge of these strains as a cause of C. difficile infection.

[Can urine albumin/creatinine ratio replace 24 hours urinary albumin?]

Objective: To analyze the correlation between urinary albumin/creatinine ratio (ACR) and 24-hour urinary microalbumin (UMA) and evaluate the predictive value of ARC for early diabetic nephropathy. Methods: A total of 368 patients with type 2 diabetes mellitus were retrospectively collected. Early diabetic nephropathy was defined as 24h UMA 30~<300 mg/24h. The correlation between ACR and 24hUMA, and the area under the receiver operating characteristic (ROC) curve of ACR in diagnosis of early diabetic nephropathy were calculated. Gender, age, course of disease, fasting venous blood glucose, glycosylated hemoglobin, blood pressure, triglyceride and total cholesterol were used as adjusting variables to establish univariate and multivariate logistic models of ACR for early diabetic nephropathy, respectively. A regression model was used to evaluate the diagnostic value of ACR for early diabetic nephropathy. Results: The correlation between ACR and 24h UMA was 0.658. The area under ROC curve of ACR for early diabetic nephropathy was 0.907 before and 0.933 after adjustments of gender, age, course of disease, fasting venous blood glucose, glycosylated hemoglobin, blood pressure, triglyceride and total cholesterol, respectively. The OR value of ACR of diabetic nephropathy was 2.016 before and 2.762 after same adjustments. The calibration of Hosmer-Lemeshow chi-square test evaluation model was 19.362 before (P=0.13) and 14.928 after adjustments (P=0.061). Conclusion: ACR is a better predictor for early diabetic nephropathy although its value is influenced by gender, age, course of disease, blood sugar, lipid, and blood pressure.

[Expression of SMARCA4(BRG1) and SMARCB1(INI1) in dedifferentiated and undifferentiated endometrial carcinomas and their correlations with clinicopathological features].

Objective: To investigate the expression of SMARCA4 (BRG1) and SMARCB1 (INI-1) protein in endometrial dedifferentiated carcinoma (DDC) and undifferentiated carcinoma (UDC), and their correlation with clinicopathologic features. Methods: Clinicopathological information was gathered for 26 cases of DDC and UDC and consulting hospitals from January, 2006 to December, 2018 in Fudan University Shanghai Cancer Center, including 10 cases of DDC and 16 cases of UDC. Morphologic features and diagnosis were reviewed by two pathologists. Immunohistochemistry for expression of BRG1 and INI1 protein was performed. The correlations with clinicopathologic features were analyzed. Results: BRG1 and INI1 loss were present in 14 of 26 cases of DDC/UDC, including 12 BRG1-deficient cases and 2 INI1-deficient cases, respectively. Six cases demonstrated variable amounts of rhabdoid cells in 14 BRG1/INI1-deficient cases, and only 1 case showed rhabdoid cells in the 12 intact expression cases. However, there was no significantly statistical difference (P=0.060). Age, invasive depth, lymph node status and FIGO stage were not associated with the expression of the BRG1 and INI1 (P=0.437, P=0.672, P=0.242, P=0.348). Remarkably, the BGR1/INI1-deficient patients had worse survival than those with intact expression (4.7 vs. 22.9, P=0.033). Conclusion: BRG1/INI1-deficient is observed in approximately half of DDC and UDC. Identification of these tumors is clinically relevant due to their more aggressive behavior and poor prognosis. Hence, BRG1 and INI1 immunohistochemical stains should be performed for DDC and UDC in order to help the pathologists to distinguish these tumors from other carcinomas, and to predict the clinical prognosis.