A fast radio burst source at a complex magnetized site in a barred galaxy.

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

Diverse polarization angle swings from a repeating fast radio burst source.

Fast radio bursts (FRBs) are millisecond-duration radio transients1,2 of unknown origin. Two possible mechanisms that could generate extremely coherent emission from FRBs invoke neutron star magnetospheres3-5 or relativistic shocks far from the central energy source6-8. Detailed polarization observations may help us to understand the emission mechanism. However, the available FRB polarization data have been perplexing, because they show a host of polarimetric properties, including either a constant polarization angle during each burst for some repeaters9,10 or variable polarization angles in some other apparently one-off events11,12. Here we report observations of 15 bursts from FRB 180301 and find various polarization angle swings in seven of them. The diversity of the polarization angle features of these bursts is consistent with a magnetospheric origin of the radio emission, and disfavours the radiation models invoking relativistic shocks.

[Analysis of factors influencing the efficacy and prognosis of surgical treatment for primary malignant pelvic bone tumors].

Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage ⅠB and 98 cases were stage ⅡB. 19 lesions were in zone Ⅰ, 1 in zone Ⅱ, 15 in zone Ⅲ, 29 in zone Ⅰ+Ⅱ, 71 in zone Ⅱ+Ⅲ, 29 in zone Ⅰ+Ⅳ, 35 in zone Ⅰ+Ⅱ+Ⅲ, 3 in zone Ⅰ+Ⅱ+Ⅳ, and 6 in zone Ⅰ+Ⅱ+Ⅲ+Ⅳ. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (P＜0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (P＜0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (P＜0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage ⅠB and ⅡB tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage ⅡB pelvic tumors was significantly lower than that of stage ⅠB tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.

[An investigation of the advantages of the adjustable angle stitch template compared with CT-guided 125I seeds free-hand implantation in the treatment of non-small cell lung carcinoma].

Objective: To investigate the advantages of adjustable angle needle path template compared with CT-guided 125I seeds free-hand implantation in the treatment of non-small cell lung carcinoma. Methods: This randomized controlled trial involved the retrospective analysis of the clinical data of 45 patients with non-small cell lung carcinoma who underwent 125I seeds implantation at the Shandong Cancer Hospital, Shaanxi Provincial Tumor Hospital and The Third Affiliated Hospital of Shandong First Medical University from May 2018 to January 2023. Patients were divided into the template (n=21) and free-hand (n=24) groups, according to the modality used. The template group comprised 16 males and 5 females, aged (66±12) years, while the free-hand group comprised 16 males and 8 females, aged (62±8) years. The dose distribution, implant quality, intraoperative computed tomography (CT) scan times, and 125I seed reseeding numbers after implantation were compared between the two groups to evaluate the potential advantages of adjustable angle needle path template-assisted implantation over free-hand 125I implantation. Results: Statistical comparison revealed no significant differences in age (t=1.16, P=0.253), tumor volume [(71±26) vs. (71±22) cm3, t=0.21, P=0.837), or any other baseline characteristics between the template and free-hand groups. Overall, 45 patients successfully completed the operation. In the template group, the mean values of the D90 (dose that was delivered to 90% of the target volume), V100 (the target volume receiving 100% of the prescription dose), coverage index (CI), relative dose homogeneity index (HI), and external volume index (EI) pre-and post-implantation were (131.0±2.1) vs. (131.1±5.5) Gy, 90.0%±0.4% vs. 91.0%±2.8%, 0.83±0.07 vs. 0.82±0.05, 41%±11% vs. 37%± 13%, and 4.3%(2.9%, 14.0%) vs.8.8%(5.2%,14.6%), respectively. None of these parameters showed any significant difference (all P>0.05). In the free-hand group, the mean value of D90 pre- and post-implantation was (131.4±2.9) vs.(128.6±8.6) Gy, showing no significant difference (P>0.05), the mean values of V100, CI, HI, and EI pre-and post-implantation were 90.0%±0.5% vs. 89.0%± 3.0%, 0.84±0.04 vs. 0.71±0.09, 41%±9% vs. 34%±10%, and 7.7% (4.9%,11.0%) vs.24.2% (14.3%, 35.3%), respectively, showing significant differences (all P<0.05). The number of reseeding seeds in the template group was lower than that in the free-hand group [2.0 (0,2.5) vs. 4.0 (2.0, 7.0), Z=-3.36, P=0.001], showing a statistically significant difference. Further, the number of CT scans in the template group was significantly less than that in the free-hand group (3.9±0.5 vs. 4.6±1.2, t=-2.54, P=0.016). The incidences of adverse reactions were 23.8% (5/21) and 33.3% (8/24) (χ2=12.86, P=0.002) in the template and free-hand groups, respectively, indicating a significant difference. Conclusion: Compared with free-hand implantation, use of the adjustable angle needle path template technique can shorten the operation time, reduce the number of scans, reduce the incidence of complications, and improve treatment efficacy to a certain extent.

[Analysis of efficacy and safety of daratumumab-containing regimen in relapsed and refractory multiple myeloma patients].

Objective: To investigate the efficacy and safety in relapsed and refractory multiple myeloma (RRMM) patients with combination regimen of daratumumab. Methods: The clinical data of 42 RRMM patients admitted to Qingdao Municipal Hospital from December 2020 to November 2023 were retrospectively analyzed, which included 26 males and 16 females, with a median age of 59 (47, 82) years old. According to the number of courses of treatment with Daratumumab, patients were divided into three groups: long course group (≥9 courses, n=21), medium course group (7-8 courses, n=12), and short course group (≤6 courses, n=9). The deadline for follow-up was November 10, 2023, and the follow-up period was 15.6 (6.0, 34.0) months. After completing at least 2 courses of treatment, patients were evaluated for efficacy, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), and progressive disease (PD). Basic clinical characteristics of patients, overall response rate of treatment, and adverse reactions were statistically analyzed. Kaplan-Meier method was used to compare the differences of progression-free survival (PFS) in patients with different courses of treatment. Results: Among the 42 patients, 15 (35.7%) had extramedullary disease or plasmacytic leukemia, 7 (16.6%) had amyloidosis, and 18 (42.9%) had renal insufficiency. In Mayo stage, 25 patients (59.5%) were at high risk of myeloma cytogenetic stratification, 8 patients (19%) were standard risk, 9 patients (21.4%) had no cytogenetic data. There were 16 patients with second-line treatment (38.0%), 13 patients with third-line treatment (31%), and 13 patients with more than fourth-line treatment (31%). All patients received at least 2 courses of treatment, achieving the best degree of disease response in 4 cases of sCR (9.5%), 3 cases of CR (7.1%), 10 cases of VGPR (23.8%), 11 cases of PR (26.2%), and 6 cases of MR (14.2%). The overall response rate (ORR) was 80.9% (34/42). The overall response rate was 100% (21/21) in the long course group, 91.6% (11/12) in the medium course group and 22.2% (2/9) in the short course group. Kaplan-Meier survival analysis showed that the duration of PFS was 5.0 (95%CI: 3.1-6.9) months in the short course group,>8.0 months in the medium course group, and>38.0 months in the long course group, the difference was statistically significant (P<0.05). Grade≥3 adverse reactions were mainly neutropenia (3 cases) and thrombocytopenia (1 case). None of the patients discontinued treatment due to adverse reactions. Conclusion: Treatment of RRMM with a regimen containing Daratumumab requires a longer course of treatment to achieve maximum efficacy and the adverse reactions can be controlled.

[Effect of adenovirus-mediated shRNA down-regulates SHP2 expression on the apoptosis of human hepatic stellate cells LX-2].

Objective: To investigate the effect of adenovirus-mediated short hairpin RNA (shRNA) downregulating SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the apoptosis of human hepatic stellate cells LX-2 cultured in vitro. Methods: The recombinant adenovirus Ad-shRNA/SHP2 carrying shRNA targeted SHP2 and expressing green fluorescent protein (GFP), and the empty control virus Ad-GFP expressing GFP were transfected into LX-2 cells cultured in vitro. Real-time fluorescence quantitative PCR was used to detect SHP2 mRNA expression in LX-2 cells. Western blot was used to detect the protein expressions of SHP2, Bax, and Bcl-2 in LX-2 cells. TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry were used to detect apoptosis in LX-2 cells. Experimental group: (1) Control group: LX-2 cells were transfected with DMEM instead of adenovirus; (2) Ad-GFP group: transfected with empty virus Ad-GFP; (3) Ad-shRNA/SHP2 group: transfected with recombinant adenovirus Ad-shRNA/SHP2. The means between multiple groups were compared using a one-way ANOVA and the LSD test was used for inter group comparisons. Results: shRNA-targeted SHP2 significantly down-regulated the expression of SHP2 protein and mRNA in LX-2 cells (P < 0.05). The TUNEL and annexin-V/propidium iodide dual-labeled flow cytometry results showed that the apoptosis rate of LX-2 cells in the Ad-shRNA/SHP2 group (12.755%±1.606%, 19.340%±2.505%) (P < 0.05) was significantly higher compared to the control group (3.077%±0.731%, 9.438%±0.804%) and the Ad-GFP group (3.250%±0.851%, 8.893%±1.982%), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). Western blot analysis of Bax and Bcl-2 protein expression in LX-2 cells of each group revealed that the Bax protein expression was significantly higher in the Ad shRNA/SHP2 group (2.493 ± 0.203) (P < 0.05) compared to the control group and Ad-GFP group (1.989 ± 0.147, 1.999 ± 0.162), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05), while the Bcl-2 protein was significantly decreased in the Ad-shRNA/SHP2 group (1.042±0.148) compared with the control group and the Ad-GFP group (1.707±0.146, 1.521±0.142), with no statistically significant difference between the control group and the Ad-GFP group (P > 0.05). Conclusions: SHP2 expression down-regulation induces apoptosis of human hepatic stellate cells LX-2 in vitro by reducing Bcl-2/Bax.

[Research progress of phage therapy in orthopedic implant-related infection].

The widespread application of implantable materials has brought about a corresponding increase in implant-related complications, with implant-associated infections being the most critical. Biofilms, which often form on these implants, can significantly impede the effectiveness of traditional antibiotic therapies. Therefore, strategies such as surgical removal of infected implants and prolonged antibiotic treatment have been acknowledged as effective measures to eradicate these infections. However,the challenges of antibiotic resistance and biofilm persistence often result in recurrent or hard-to-control infections, posing severe health threats to patients. Recent studies suggest that phages, a type of virus, can directly eliminate pathogenic bacteria and degrade biofilms. Furthermore, clinical trials have demonstrated promising therapeutic results with the combined use of phages and antibiotics. Consequently, this innovative therapy holds significant potential as an effective solution for managing implant-associated infections. This paper rigorously investigates and evaluates the potential value of phage therapy in addressing orthopedic implant-associated infections, based on a comprehensive review of relevant scientific literature.

[The impact of extended waiting time on tumor regression after neoadjuvant chemoradiotherapy for locally advanced rectal cancer].

Objective: To investigate the influence of extending the waiting time on tumor regression after neoadjuvant chemoradiology (nCRT) in patients with locally advanced rectal cancer (LARC). Methods: Clinicopathological data from 728 LARC patients who completed nCRT treatment at the First Affiliated Hospital, Naval Medical University from January 2012 to December 2021 were collected for retrospective analysis. The primary research endpoint was the sustained complete response (SCR). There were 498 males and 230 females, with an age (M(IQR)) of 58 (15) years (range: 22 to 89 years). Logistic regression models were used to explore whether waiting time was an independent factor affecting SCR. Curve fitting was used to represent the relationship between the cumulative occurrence rate of SCR and the waiting time. The patients were divided into a conventional waiting time group (4 to <12 weeks, n=581) and an extended waiting time group (12 to<20 weeks, n=147). Comparisons regarding tumor regression, organ preservation, and surgical conditions between the two groups were made using the t test, Wilcoxon rank sum test, or χ2 test as appropriate. The Log-rank test was used to elucidate the survival discrepancies between the two groups. Results: The SCR rate of all patients was 21.6% (157/728). The waiting time was an independent influencing factor for SCR, with each additional day corresponding to an OR value of 1.010 (95%CI: 1.001 to 1.020, P=0.031). The cumulative rate of SCR occurrence gradually increased with the extension of waiting time, with the fastest increase between the 10th week. The SCR rate in the extended waiting time group was higher (27.9%(41/147) vs. 20.0%(116/581), χ2=3.901, P=0.048), and the organ preservation rate during the follow-up period was higher (21.1%(31/147) vs. 10.7%(62/581), χ2=10.510, P=0.001). The 3-year local recurrence/regrowth-free survival rates were 94.0% and 91.1%, the 3-year disease-free survival rates were 76.6% and 75.4%, and the 3-year overall survival rates were 95.6% and 92.2% for the conventional and extended waiting time groups, respectively, with no statistical differences in local recurrence/regrowth-free survival, disease-free survival and overall survival between the two groups (χ2=1.878, P=0.171; χ2=0.078, P=0.780; χ2=1.265, P=0.261). Conclusions: An extended waiting time is conducive to tumor regression, and extending the waiting time to 12 to <20 weeks after nCRT can improve the SCR rate and organ preservation rate, without increasing the difficulty of surgery or altering the oncological outcomes of patients.

[Comparative study of gap balancing and measured resection technique in patients receiving staged bilateral total knee arthroplasty].

Objective: To compare the clinical outcomes of staged total knee arthroplasty (TKA) performed on both knees in the same patient using gap balancing (GB) and measured resection (MR) techniques, respectively. Methods: The clinical data of 57 patients undergoing bilateral staged TKA at the Xi'an Jiaotong University Affiliated Honghui Hospital from July 2018 to January 2020 were analyzed. Using the random number table, MR or GB technique was selected when patients underwent primary TKA, and contralateral procedure was done with another technique. The procedures were performed by one chief surgeon, and the same prosthesis was chosen for all the procedures. The two osteotomy techniques for TKA were compared in terms of surgical status, radiographic data, functional recovery and satisfaction rate. Results: Total of 57 patients, including 16 males and 41 females, were included in the study with a mean age of (68.5±4.6) years (59-79 years) at primary TKA. All patients were followed up for (29.6±4.5) months (22-39 months). The interval between the two procedures was (4.7±3.0) months (0.5-12.0 months). Postoperative drainage was less in the GB side when compared with that in the MR side [(93.6±22.2) ml vs (109.9±36.9) ml, P=0.003]. At the 1-month postoperative follow-up, the visual analogue scale (VAS) of pain was lower on the GB side (3.0±0.8) than on the MR side (3.5±1.2), the range of motion (ROM) was higher on the GB side (105.7°±8.2° vs 100.2°±7.5°), the Knee Society Score (KSS) was higher on the GB side (78.5±5.4 vs 74.2±6.3), and the Western Ontario and McMaster University (WOMAC) score was lower on the GB side (35.4±5.5 vs 38.0±6.3), there were significant differences in the up-mentioned indexes between the two groups (all P<0.05). However, the repeated-measures analysis of variance indicated that there was no significant difference in VAS score, ROM, KSS score and WOMAC score between the two techniques (all P>0.05). The satisfactory rate of GB technique was 84.2%(48/57), ant it was 86.0%(49/57) with MR technique (P=0.446). There was also no significant difference between the two techniques in terms of complications (P=0.754). Conclusion: Both the GB and MR technique result in good knee function with similar clinical outcomes in patients receiving TKA in both knees for osteoarthritis without significant deformity.

[Epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea from 2013 to 2019 in Pudong New Area, Shanghai].

Objective: To investigate the epidemiological characteristics of Yersinia enterocolitica in patients with diarrhea in Pudong New Area, Shanghai. Methods: Active surveillance of diarrhea was conducted in 14 sentinel hospitals (three tertiary-level hospitals, nine secondary-level hospitals, and two primary-level hospitals) from January 2013 to December 2019 in Pudong New Area of Shanghai, China base on their location, catchment area, and patient volume. Cold enrichment method was used to isolate Y. enterocolitica and further detection of bioserotype, virulence genes and antimicrobial susceptibility of the isolates were conducted. The difference of rates was determined using chi-square test or Fisher's exact test. Results: A total of 12 941 diarrhea cases were included, and 0.7% (88/12 941) cases were confirmed with Yersinia enterocolitica infection. 67.0% (59/88) cases were single infection, 33.0% (29/88) cases were mixed infections. Detection rates of Y. enterocolitica increased annually (0.3%-1.2%) and were highest in children<5 years of age (1.1%, 37/3 218) and in spring (1.1%, 32/2 998) (χ2 were 18.64 and 9.76, respectively, P<0.05). 58.0% (51/88) cases had watery diarrhea, 15.9% (14/88) had fever and 14.8% (13/88) had vomiting. The predominant bioserotypes were 3/O:3 (53.4%, 47/88), followed by 1A/O:8 (15.9%, 14/88) and 1A/O:5(6.8%, 6/88), respectively. Bioserotype 3/O:3 counted for the highest proportions (89.2%, 33/37) in children <5 years of age. All the strains of bioserotype 3/O:3 harbored ail, ystA, yadA and virF genes, which encoded pathogenic Y. enterocolitica. 11/14 strain of 1A/O:8 and 4/6 strains of 1A/O:5 harbored ystB gene. Most strains were resistant to ampicillin (80.7%,71/88) and amoxicillin/clavulanic acid (71.6%,63/88), and 63.8% (56/88) strains were multidrug resistance (MDR). The difference of antimicrobial resistance rates between 3/O:3 and non 3/O:3 was statistically significant in ampicillin, cefoxitin, nalidixic acid, tetracycline and ampicillin/sulbactam (χ2 was 14.68, 43.80, 41.86, 30.54 and 5.07, respectively, P<0.05). Conclusion: The detection rate of Yersinia enterocolitica was higher in children than in adults in Pudong New Area, Shanghai. The predominant bioserotype was pathogenic 3/O:3 with multidrug resistance.

[Analysis of the usage of post-exposure prophylaxis and related factors among men who have sex with men].

A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income<5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(OR=3.87, 95%CI:1.12-13.36),monthly income≥5 000 yuan(OR=1.87, 95%CI:1.07-3.28),commercial sex (OR=3.13, 95%CI:1.56-6.28), drug users (DUs) (OR=4.63, 95%CI:2.51-8.52),STD patient (OR=2.35,95%CI:1.05-5.27),the mixed sex role group(OR=2.25,95%CI:1.10-4.62).

[Effects of adenovirus-mediated shRNA down-regulates PTEN expression on fibril-binding proteins vinculin, filamin A and cortactin in activated hepatic stellate cells].

Objective: To investigate the effect of adenovirus-mediated shRNA down-regulating phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression on vinculin, filamin A, and cortactin in activated hepatic stellate cells (HSCs). Methods: Activated rats hepatic stellate cell line (HSC-T6) was cultured in vitro. Recombinant adenovirus Ad-shRNA/PTEN carrying PTEN targeted RNA interference sequence [short hairpin RNA (shRNA)] and empty control virus Ad-GFP were transfected into HSCs. The PTEN mRNA and protein expression of HSCs in each group were detected by real-time fluorescence quantitative PCR and Western blot. The expressional change of vinculin, filamin A and cortactin in HSCs of each group were detected by confocal laser scanning immunofluorescence microscope. Image-pro plus 6.0 software was used for image analysis and processing. The integrated optical density (IOD) of the fluorescence protein expression was measured. The experiment was divided into three groups: control group (DMEM instead of adenovirus solution in the adenovirus transfection step), Ad-GFP group (transfected with empty virus Ad-GFP only expressing green fluorescent protein), and Ad-shRNA/PTEN group (recombinant adenovirus Ad-shRNA/PTEN carrying shRNA targeting PTEN and expressing green fluorescent protein). One-way analysis of variance was used for comparison of mean value among the three groups, and LSD-test was used for comparison between the groups. Results: shRNA targeted PTEN was successfully transfected and the expression of PTEN mRNA and protein in HSC (P < 0.05) was significantly down-regulated. HSCs vinculin was mainly expressed in the cytoplasm. HSCs vinculin fluorescence IOD in the Ad-shRNA/PTEN group (19 758.83 ± 1 520.60) was higher than control (7 737.16 ± 279.93) and Ad-GFP group (7 725.50 ± 373.03) (P < 0.05), but there was no statistically significant difference between control group and Ad-GFP group (P > 0.05). There was no statistically significant difference in the fluorescence IOD of Filamin A among the three groups (P > 0.05), but the subcellular distribution of Filamin A among the three groups were changed. Filamin A in the Ad-shrNA /PTEN HSC group was mainly distributed in the cytoplasm. Filamin A HSC was mainly located in the nucleus.The filamin A HSC in the control group and Ad-GFP group was mainly located in the nucleus. The nucleocytoplasmic ratio of Filamin A in the AD-shrNA /PTEN group (0.60 ± 0.15) was significantly lower than control group (1.20 ± 0.15) and Ad-GFP group (1.08 ± 0.23), P < 0.05. but there was no statistically significant difference in filamin A nucleocytoplasmic ratio of HSC between the control group and the Ad-GFP group (P > 0.05). Cortactin HSCs in the three groups was mainly distributed in the cytoplasm. The cortactin fluorescence IOD of HSCs in the Ad-shRNA/PTEN group was significantly higher than control group (22 959.94 ± 1 710.42) and the Ad-GFP group (22 547.11 ± 1 588.72 ) (P < 0.05), while there was no statistically significant difference in the IOD of cortactin fluorescence in HSCs between the control group and the Ad-GFP group (P > 0.05). Conclusion: The down-regulation of PTEN expression raises the expression of microfilament-binding protein vinculin and cortactin, and changes the subcellular distribution of another microfilament binding protein filamin A, that is, translocation from nucleus to the cytoplasm in activated HSC in vitro.

[Characteristics of the immune microenvironment and related treatment strategies in patients with periprosthetic joint infection].

Periprosthetic joint infection (PJI) involves complex immunomodulatory interactions between pathogens,biomaterials,and hosts,and correlates with alterations in the ratio of immune cells as well as in the concentration of immune checkpoint molecules.Prosthesis,biofilm,microorganisms,and host constitute a special and complex immune microenvironment.Fully studying the characteristics of immune microenvironment and potential targets of immunotherapy in orthopedic implant-associated infections are expected to provide a new direction for clinical treatment of PJI. An overview of the literature related to PJI and immune regulation at domestic and international sites was conducted to summarize and analyze the characteristics of the immune microenvironment and the potential value of related immunotherapy, aiming to provide new insights for the targeted treatment of PJI.

A framework for automated gene selection in genomic applications.

PURPOSE: An efficient framework to identify disease-associated genes is needed to evaluate genomic data for both individuals with an unknown disease etiology and those undergoing genomic screening. Here, we propose a framework for gene selection used in genomic analyses, including applications limited to genes with strong or established evidence levels and applications including genes with less or emerging evidence of disease association. METHODS: We extracted genes with evidence for gene-disease association from the Human Gene Mutation Database, OMIM, and ClinVar to build a comprehensive gene list of 6,145 genes. Next, we applied stringent filters in conjunction with computationally curated evidence (DisGeNET) to create a restrictive list limited to 3,929 genes with stronger disease associations. RESULTS: When compared to manual gene curation efforts, including the Clinical Genome Resource, genes with strong or definitive disease associations are included in both gene lists at high percentages, while genes with limited evidence are largely removed. We further confirmed the utility of this approach in identifying pathogenic and likely pathogenic variants in 45 genomes. CONCLUSION: Our approach efficiently creates highly sensitive gene lists for genomic applications, while remaining dynamic and updatable, enabling time savings in genomic applications.

Reduced postprandial bone resorption and greater rise in GLP-1 in overweight and obese individuals after an α-glucosidase inhibitor: a double-blinded randomized crossover trial.

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

[Dynamic expression of protein tyrosine phosphatase SHP2 in liver tissue of rats with carbon tetrachloride-induced liver fibrosis].

Objective: To investigate the dynamic expression of protein tyrosine phosphatase SHP2 in liver tissue of rats with carbon tetrachloride (CCl(4))-induced liver fibrosis. Methods: Rat liver fibrosis model was established by intraperitoneal injection of CCl(4). Rat liver tissue histopathological changes were detected by HE and Masson-trichrome staining. Immunohistochemical staining, Western blot and real-time fluorescent quantitative PCR were used to detect SHP2 protein and mRNA expression in rat liver tissue. One-way analysis of variance was used for the comparison of means between multiple groups, and the LSD test was used for further inter-group comparison. Results: CCl(4)-induced rat liver fibrosis model was successfully constructed, and with the extension of modeling time, the degree of liver fibrosis in rats were aggravated gradually. Immunohistochemical staining results showed that SHP2 was mainly expressed in the cytoplasm of rat liver tissues. With the aggravation of liver fibrosis, the number of cells with positive expression of SHP2 was aggravated gradually (P < 0.05). Western blot and real-time fluorescent quantitative PCR results showed that the expressions of SHP2 protein and mRNA in rat fibrotic liver tissues at different times in week 2, 4, 6, and 8 were higher in modeling than control group (P < 0.05), and was aggravated gradually with the liver fibrosis aggravation (P < 0.05). Conclusion: The expression of SHP2 protein and mRNA in the liver tissue of rats with CCl(4)-induced liver fibrosis increased gradually with the degree of liver fibrosis, and the degree of increase was consistent with the degree of liver fibrosis.

Effects of Bacillus methylotrophicus M4-1 on physiological and biochemical traits of wheat under salinity stress.

AIM: The aim of this study was to evaluate the ability of Bacillus methylotrophicus M4-1 to protect winter wheat from the harmful effects of soil salinity and alkalinity. METHODS AND RESULTS: We isolated the halotolerant B. methylotrophicus M4-1. Two representative soils with different salt contents (S1, 213 µs cm-1 ; S2, 786 µs cm-1 ) in the Yellow River delta region of China were selected for experiments. The effects of the M4-1 strain on the typical wheat variety (Jimai 21) in this environment were proven. In S1 soil, the M4-1 strain reduced the wheat rhizosphere soil pH (1·61%) and electrical conductivity (EC) (8·01%) and increased the exchangeable K content (11·14%). The uptake of Mg2+ (20·73%) by wheat roots and K+ (8·84%) by leaves was increased, and the content of Na+ (23·62%) in leaves was reduced. In S2 soil, the M4-1 strain was able to reduce soil EC (2·56%) and increase exchangeable K (11·20%) content. The absorption of K+ (13·28%) in wheat leaves was increased, and the content of Na+ (12·41%) in roots was decreased. Total N and organic matter contents in rhizosphere soil were significantly positively correlated with wheat growth and salt tolerance, whereas EC showed a significant negative correlation. CONCLUSIONS: M4-1 attenuates salt stress injury in wheat under both low and high salt stress. SIGNIFICANCE AND IMPACT OF THE STUDY: We demonstrated the efficacy and value of plant growth-promoting rhizobacteria addition to protect winter wheat against salt stress and improve crop yield. We also elucidated the physicochemical and biochemical interactions among M4-1, the rhizosphere and the host plant.

A higher level of total bile acid in early mid-pregnancy is associated with an increased risk of gestational diabetes mellitus: a prospective cohort study in Wuhan, China.

PURPOSE: To assess the longitudinal associations between maternal total bile acid (TBA) levels during early mid-pregnancy and the subsequent risk of gestational diabetes mellitus (GDM). METHODS: In a prospective cohort study, pregnant women who were enrolled prior to gestational week 16 were followed until delivery. TBA levels were tested during weeks 14-18 of gestation. Using logistic regression, we analyzed the associations between quartiles of TBA and GDM based on a 75-g oral glucose tolerance test (OGTT) at 24-28 gestational weeks. RESULTS: The GDM rate was 7.9% (114/1441). The mean TBA level was higher in women with GDM than in those without GDM (2.1 ± 2.0 vs 1.5 ± 1.0 µmol/L, P = 0.000). The highest TBA level quartile (2.1-10.7 µmol/L) had a 1.78-fold (95% CI 1.01, 3.14) increased risk of GDM compared with that of the lowest quartile (0.0-0.8 µmol/L) after adjusting for pre-pregnancy body mass index (BMI), gestational, age at TBA test and other confounders. High TBA levels were involved in the fasting glucose level rather than that at 1 h and 2 h after OGTT in all participants. CONCLUSIONS: Pregnant women with higher serum TBA levels during early mid-pregnancy have a higher risk of developing GDM. TBA may be a new risk factor for GDM.

Effects of different types of zinc supplement on the growth, incidence of diarrhea, immune function, and rectal microbiota of newborn dairy calves.

Neonatal diarrhea in dairy calves causes huge economic and productivity losses in the dairy industry. Zinc is an effective anti-diarrheal agent, but high doses may pose a threat to the environment. Therefore, we aimed to evaluate the effects of low-dose zinc supplementation on the growth, incidence of diarrhea, immune function, and rectal microbiota of newborn Holstein dairy calves. Thirty newborn calves were allocated to either a control group (without extra zinc supplementation), or groups supplemented with either 104 mg of zinc oxide (ZnO, equivalent to 80 mg of zinc/d) or 457 mg of zinc methionine (Zn-Met, equivalent to 80 mg of zinc/d) and studied them for 14 d. The rectal contents were sampled on d 1, 3, 7, and 14, and blood samples were collected at the end of the study. Supplementation with ZnO reduced the incidence of diarrhea during the first 3 d of life, and increased serum IgG and IgM concentrations. The Zn-Met supplementation increased growth performance and reduced the incidence of diarrhea during the first 14 d after birth. The results of fecal microbiota analysis showed that Firmicutes and Proteobacteria were the predominant phyla, and Escherichia and Bacteroides were the dominant genera in the recta of the calves. As the calves grew older, rectal microbial diversity and composition significantly evolved. In addition, dietary supplementation with ZnO reduced the relative abundance of Proteobacteria in 1-d-old calves, and increased that of Bacteroidetes, Lactobacillus, and Faecalibacterium in 7-d-old calves, compared with the control group. Supplementation with Zn-Met increased the relative abundance of the phylum Actinobacteria and the genera Faecalibacterium and Collinsella on d 7, and that of the genus Ruminococcus after 2 wk, compared with the control group. Thus, the rectal microbial composition was not affected by zinc supplementation but significantly evolved during the calves' early life. Zinc supplementation reduced the incidence of diarrhea in young calves. In view of their differing effects, we recommend ZnO supplementation for dairy calves during their first 3 d of life and Zn-Met supplementation for the subsequent period. These findings suggest that zinc supplementation may be an alternative to antibacterial agents for the treatment of newborn calf diarrhea.