Characterization of "Off-Target" Immune Modulation Induced by Live Attenuated Yellow Fever Vaccine.

BACKGROUND: Live attenuated vaccines alter immune functions and are associated with beneficial outcomes. We previously demonstrated that live attenuated yellow fever virus (YFV) vaccine (LA-YF-Vax) dampens T-cell receptor (TCR) signaling in vitro via an RNA-based mechanism. We examined study participants before and after LA-YF-Vax to assess TCR-mediated functions in vivo. METHODS: Serum samples and peripheral blood mononuclear cells (PBMCs) were obtained before and after LA-YF-Vax (with or without additional vaccines) or quadrivalent influenza vaccine. TCR-mediated activation was determined by interleukin 2 release or phosphorylation of the lymphocyte-specific Src kinase. TCR-regulating phosphatase (protein tyrosine phosphatase receptor type E [PTPRE]) expression was also measured. RESULTS: Compared with prevaccination findings, LA-YF-Vax recipient PBMCs demonstrated transient reduction in interleukin 2 release after TCR stimulation and PTPRE levels, unlike in control participants who received quadrivalent influenza vaccine. YFV was detected in 8 of 14 participants after LA-YF-Vax. After incubation of healthy donor PBMCs in serum-derived extracellular vesicles prepared from LA-YF-Vax recipients, TCR signaling and PTPRE levels were reduced after vaccination, even in participants without detectable YFV RNA. CONCLUSIONS: LA-YF-Vax reduces TCR functions and PTPRE levels after vaccination. Extracellular vesicles from serum recapitulated this effect in healthy cells. This likely contributes to the reduced immunogenicity for heterologous vaccines after LA-YF-Vax administration. Identification of specific immune mechanisms related to vaccines should contribute to understanding of the "off-target," beneficial effects of live vaccines.

Perfusion of hepatocellular carcinomas measured by diffusion-derived vessel density biomarker: Higher hepatocellular carcinoma perfusion than earlier intravoxel incoherent motion reports.

Diffusion-derived vessel density (DVDD) is a physiological surrogate of the area of microvessels per unit tissue area. DDVD is calculated according to DDVD(b0b2) = Sb0/ROIarea0 - Sb2/ROIarea2, where Sb0 and Sb2 refer to the liver signal when b is 0 or 2 s/mm2. Pathohistological studies and contrast-enhanced CT/MRI data showed higher blood volume in hepatocellular carcinoma (HCC) relative to native liver tissue. With intravoxel incoherent motion (IVIM) imaging, most authors paradoxically reported a decreased perfusion fraction of HCC relative to the adjacent liver. This study applied DDVD to assess the perfusion of HCC. MRI was performed with a 3.0-T magnet. Diffusion-weighted images with b-values of 0 and 2 s/mm2 were acquired in 72 HCC patients. Thirty-two patients had microvascular invasion (MVI(+)) and 40 patients did not have microvascular invasion (MVI(-)). Fifty-eight patients had Edmondson-Steiner grade I or II HCC, and 14 patients had Edmondson-Steiner grade III or IV HCC. DDVD measurement was conducted on the axial slice that showed the largest HCC size. DDVD(b0b2) T/L = HCC DDVD(b0b2)/liver DDVD(b0b2). DDVD(b0b2) T/L median (95% confidence interval) of all HCCs was 2.942 (2.419-3.522), of MVI(-) HCCs was 2.699 (2.030-3.522), of MVI(+) HCCs was 2.988 (2.423-3.990), of Edmondson-Steiner grade I/II HCCs was 2.873 (2.277-3.465), and of Edmondson-Steiner grade III/IV HCCs was 3.403 (2.008-4.485). DDVD(b0b2) T/L approximately agrees with contrast agent dynamically enhanced CT/MRI literature data, whereas it differs from earlier IVIM study results, where HCC perfusion fraction was paradoxically lower relative to native liver tissue. A weak trend was noted with MIV(+) HCCs had a higher DDVD(b0b2) T/L than that of MVI(-) HCCs, and a weak trend was noted with the poorly differentiated group of HCCs (Edmondson-Steiner grade III and IV) had a higher DDVD(b0b2) T/L than that of the better differentiated group of HCCs (Edmondson-Steiner grade I and II).

Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences.

For liver intravoxel incoherent motion (IVIM) data acquisition, respiratory-triggering (RT) MRI is commonly used, and there are strong motivations to shorten the scan duration. For the same scan duration, more b values or higher numbers of excitations can be allowed for free-breathing (FB) imaging than for RT. We studied whether FB can be used to replace RT when careful IVIM image acquisition and image processing are conducted. MRI data of 22 healthy participants were acquired using a 3.0 T scanner. Diffusion imaging was based on a single-shot spin-echo-type echo-planar sequence and 16 b values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, and 600 s/mm2 . Each subject attended two scan sessions with an interval of 10-20 days. For each scan session, a subject was scanned twice, first with RT and then with FB. The mean image acquisition time was 5.4 min for FB and 10.8 min for RT. IVIM parameters were calculated with bi-exponential model segmented fitting with a threshold b value of 60 s/mm2 , and fitting started from b = 2 s/mm2 . There was no statistically significant difference between IVIM parameters measured with FB imaging or RT imaging. Perfusion fraction ICC (intraclass correlation coefficient) for FB imaging and RT imaging in the same scan session was 0.824. For perfusion fraction, wSD (within-subject standard deviation), BA (Bland-Altman) difference, BA 95% limit, and ICC were 0.022, 0.0001, -0.0635~0.0637, and 0.687 for FB and 0.031, 0.0122, -0.0723~0.0967, and 0.611 for RT. For Dslow (×10-3  s/mm2 ), wSD, BA difference, BA 95% limit, and ICC were 0.057, 0.0268, -0.1258~0.1793, and 0.471 for FB and 0.073, -0.0078, -0.2170-0.2014, and <0.4 for RT. The Dfast coefficient of variation was 0.20 for FB imaging and 0.28 for RT imaging. All reproducibility indicators slightly favored FB imaging.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older Chinese men can be the same as that of older Chinese women, both much lower than the value for Caucasians.

For older Caucasian women and men, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) threshold for classifying osteoporosis is 80 mg/ml. It was recently proposed that, for older East Asian women, the QCT LS BMD value equivalent to the Caucasian women's threshold of 80 mg/mL is about 45∼50 mg/ml. For a data of 328 cases of Chinese men (age: 73.6 ± 4.4 years) who had QCT LS BMD and DXA LS BMD at the same time and with the DXA BMD value of ≤ 0.613 g/cm2 to classify osteoporosis, the corresponding QCT LS BMD threshold is 53 mg/ml. Osteoporotic-like vertebral fracture sum score (OLVFss) ≤ -2.5 has been proposed to diagnose osteoporosis. For 316 cases of Chinese men (age:73.7±4.5 years), OLVFss ≤ -2.5 defines an osteoporosis prevalence of 4.4%; to achieve this osteoporosis prevalence, the corresponding QCT LS BMD value is < 47.5 mg/ml. In the China Action on Spine and Hip Status study, a Genant grades 2/3 radiographic 'osteoporotic vertebral fracture' prevalence was 2.84% for Chinese men (total n = 1267, age: 62.77 ± 9.20 years); to achieve this osteoporosis prevalence, the corresponding BMD value was < 42.5 mg/ml. In a study of 357 Beijing older men, according to the clinical fragility fracture prevalence and femoral neck DXA T-score, the QCT LS BMD value to classify osteoporosis was between 39.45 mg/ml and 51.38 mg/ml. For older Chinese men (≥ 50 years), we recommend the cutpoint for the QCT LS BMD definition of osteoporosis to be 45∼50 mg/ml which is the same as the value for Chinese women.

Much lower prevalence and severity of spine degenerative changes among older Chinese women than among older Caucasian women and its implication for the interpretation of lumbar spine BMD T-score for Chinese women.

The prevalence and severity of spine degenerative changes have been noted to be lower among older Chinese women than among older Caucasian women. Spine degenerative changes associated with marginal osteophytosis, trabecular thickening, subchondral sclerosis, facet joint arthrosis, and disc space narrowing can all lead to artificially higher spine areal bone mineral density (BMD). The lower prevalence and severity of spine degeneration have important implications for the interpretation of spine areal BMD reading for Chinese women. With fewer contributions from spine degenerative changes, following natural aging, the declines of population group means of spine BMD and T-score are faster for Chinese women than for Caucasian women. While a cutpoint T-score ≤ -2.5 for defining spine densitometric osteoporosis is recommended for Caucasian women, for Chinese women the same cutpoint T-score of ≤ -2.5 inflates the estimated osteoporosis prevalence based on spine BMD measure. In addition to the use of an ethnicity-specific BMD reference database, a stricter cutpoint T-score for defining spine densitometric osteoporosis among older Chinese women should be applied.

Quantitative CT lumbar spine BMD cutpoint value for classifying osteoporosis among older East Asian women should be lower than the value for Caucasians.

For Caucasian women, the QCT (quantitative CT) lumbar spine (LS) bone mineral density (BMD) cutpoint value for classifying osteoporosis is 80 mg/ml. At the age of approximate 78 years, US Caucasian women QCT LS BMD population mean is 80 mg/ml, while that of Chinese women and Japanese women is around 50 mg/ml. Correlation analyses show, for Chinese women and Japanese women, QCT LS BMD of 45 mg/ml corresponds to the dual-energy X-ray absorptiometry cutpoint value for classifying osteoporosis. For Chinese and Japanese women, if QCT LS BMD 80 mg/ml is used as the threshold to classify osteoporosis, then the specificity of classifying subjects with vertebral fragility fracture into the osteoporotic group is low, whereas threshold of 45 mg/ml approximately achieve a similar separation for women with and without vertebral fragility fracture as the reports for Caucasian women. Moreover, by using 80mg/ml as the cutpoint value, LS QCT leads to excessively high prevalence of osteoporosis for Chinese women, with the discordance between hip dual-energy X-ray absorptiometry and LS QCT measures far exceeding expectation. Considering the different bone properties and the much lower prevalence of fragility fractures in the East Asian women compared with Caucasians, we argue that the QCT cutpoint value for classifying osteoporosis among older East Asian women will be close to and no more than 50 mg/ml LS BMD. We suggest that it is also imperative the QCT osteoporosis classification criterion for East Asian male LS, and male and female hips be re-examined.

East Asians' T-scores for the diagnosis of osteoporosis should be calculated using ethnicity- and gender-specific BMD reference ranges: justifications.

The 2013 ISCD consensus recommended a Caucasian female reference database for T-score calculation in men, which says "A uniform Caucasian (non-race adjusted) female reference database should be used to calculate T-scores for men of all ethnic groups." However, this statement was recommended for the US population, and no position was taken with respect to BMD reference data or ethnicity matching outside of the USA. In East Asia, currently, a Japanese BMD reference database is universally adopted in Japan for clinical DXA diagnosis, while both local BMD and Caucasian BMD reference databases are in use in Mainland China, South Korea, Taiwan, and Singapore. In this article, we argue that an ethnicity- and gender-specific BMD database should be used for T-score calculations for East Asians, and we list the justifications why we advocate so. Use of a Caucasian BMD reference database leads to systematically lower T-scores for East Asians and an overestimation of the prevalence of osteoporosis. Using a female BMD reference database to calculate T-scores for male patients leads to higher T-score values and an underestimation of the prevalence of osteoporosis. Epidemiological evidence does not support using a female BMD reference database to calculate T-scores for men. We also note that BMD reference databases collected in Asia should be critically evaluated for their quality.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.

Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

The observation that older men suffer from hip fracture at DXA T-scores higher than older women and a proposal of a new low BMD category, osteofrailia, for predicting fracture risk in older men.

The clinical significance of osteoporosis lies in the occurrence of fragility fractures (FFx), and the most relevant fracture site is the hip. The T-score is defined as follows: (BMDpatient-BMDyoung adult mean)/SDyoung adult population, where BMD is bone mineral density and SD is the standard deviation. When the femoral neck (FN) is measured in adult Caucasian women, a cutpoint value of patient BMD of 2.5 SD below the young adult mean BMD results in a prevalence the same as the lifetime risk of hip FFx for Caucasian women. The FN T-score criterion for classifying osteoporosis in older Caucasian men has been provisionally recommended to be - 2.5, but debates remain. Based on a systematic literature review, we noted that older men suffer from hip FFx at a FN T-score approximately 0.5-0.6 higher than older women. While the mean hip FFx FN T-score of around - 2.9 for women lies below - 2.5, the mean hip FF FN T-score of around - 2.33 for men lies above - 2.5. This is likely associated with that older male populations have a higher mean T-score than older female populations. We propose a new category of low BMD status, osteofrailia, for older Caucasian men with T-score ≤ - 2 (T-score ≤ - 2.1 for older Chinese men) who are likely to suffer from hip FFx. The group with T-score ≤ - 2 for older Caucasian men is comparable in prevalence to the group with T-score ≤ - 2.5 for older Caucasian women. However, older men in such category on average have only half the FFx risk as that of older women with osteoporotic T-score.

Triple-negative breast cancer: predictive model of early recurrence based on MRI features.

AIM: To develop an integrated model based on preoperative magnetic resonance imaging (MRI) features for predicting early recurrence in patients with triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Women with TNBC who underwent breast MRI and surgery between 2009 and 2019 were evaluated retrospectively. Two breast radiologists reviewed MRI images independently based on the Breast Imaging Reporting and Data System Lexicon (BI-RADS), and classified the breast oedema scores on T2-weighted imaging (WI) as no oedema, peritumoural oedema, prepectoral oedema, or subcutaneous oedema. The relationship between disease-free survival (DFS) and MRI features was analysed by Cox regression, and a nomogram model was generated based on the results. RESULTS: 150 patients with TNBC were included and divided into a training cohort (n=78) and validation cohort (n=72). MRI features including subcutaneous oedema and rim enhancement showed a tendency to worsen DFS in univariate analysis. Multivariate analysis showed that subcutaneous oedema (p=0.049, HR [95% confidence interval {CI} = 8.24 [1.01-67.52]) and rim enhancement (p=0.016, HR [95% CI] = 4.38 [1.32-14.54]) were independent predictors for DFS. In the nomogram, the areas under the curves (AUCs) of the training cohort was 0.808, and that of the validation cohort was 0.875. CONCLUSION: The presence of subcutaneous oedema or rim enhancement on preoperative breast MRI was shown to be a good predictor of poor survival outcomes in patients with TNBC.

Newly proposed survival staging system for poorly differentiated thyroid cancer: a SEER-based study.

OBJECTIVE: Despite the recent release of the 8th edition TNM staging system, the risk stratification for poorly differentiated thyroid cancer (PDTC) remains controversial. STUDY DESIGN: Retrospective study. SETTING: SEER database and the First Hospital of China Medical University (FHCMU) database. METHODS: Between 2004 and 2015, 1201 PDTC patients from the SEER database were enrolled to propose a new staging system. 38 PDTC patients were included from the FHCMU. RESULTS: A retrospective analysis of 1201 PDTC cases was performed, and a new staging classification was developed as follows: stage I: age < 55 and T1/any N/M0 (n = 127, 10.57%); stage II: age < 55 and T2-4/any N/M0 or age ≥ 55 and T1-2/any N/M0 (n = 523, 43.55%); stage III: age < 55 and any T/N0/M1 or age ≥ 55 and any T3/any N/M0 (n = 239, 19.90%); stage IV: age < 55 and any T/N1/M1 or age ≥ 55 and T4/any N/M0, and T/any N/M1 (n = 312, 25.98%). The 10-year disease-specific survival rates of patients in the new stages I, II, III, and IV were 97.9%, 77.9%, 35.3%, and 12.1%, respectively. The proportion of variation explained (PVE) for disease-specific survival of the proposed system was higher than that of the 8th AJCC TNM staging (30.61% vs. 27.15%). The accuracy of the staging system was verified in 38 PDTC patients from the FHCMU. CONCLUSION: The proposed staging system provided a more accurate risk stratification for PDTC patients. The new staging model may facilitate the design of personalized treatment strategies for PDTC patients.

Comparison of anal function and quality of life after conformal sphincter preservation operation and intersphincteric resection of very low rectal cancer: a multicenter, retrospective, case-control analysis.

PURPOSE: Conformal sphincter preservation operation (CSPO) is a sphincter preservation operation for very low rectal cancers. Compared to intersphincteric resection (ISR), CSPO retains more dentate line and distal rectal wall, and also avoids damaging the nerves in the intersphincteric space. This study aimed to compare the postoperative anal function and quality of life between the CSPO and ISR. METHOD: Patients with low rectal cancer undergoing CSPO (n = 117) and ISR (n = 66) were included from Changhai and Huashan Hospital, respectively, between 2011 and 2020. A visual analog scale (range 0-10) was utilized to evaluate satisfaction with anal function and quality of life. The anal function was evaluated with Wexner scores and low anterior resection syndrome (LARS) score. Quality of life was evaluated with the EORTC QLQ-C30 and QLQ-CR38. RESULTS: The CSPO group had more male patients (65.8% vs. 50%, p = 0.042), more preoperative chemoradiotherapy (33.3% vs. 10.6%, p < 0.001), lower tumor position (3.45 ± 1.13 vs. 4.24 ± 0.86 cm, p < 0.001), and more postoperative chemotherapy (65% vs. 13.6%, p < 0.001) compared to the ISR group. In addition, CSPO patients had shorter postoperative stay (6.63 ± 2.53 vs. 7.85 ± 4.73 days, p = 0.003) and comparable stoma reversal rates within 1 year after surgery (92.16% vs. 96.97%, p = 0.318). Multivariable analysis showed that CSPO significantly contributed to higher satisfaction with anal function (beta = 1.752, 95% CI 0.776-2.728) and with quality of life (beta = 1.219, 95% CI 0.374-2.064), but not to Wexner, LARS score, or EORTC QLQ-C30 and QLQ-CR38. CONCLUSION: CSPO improved the satisfaction with anal function and quality of life but utilized more preoperative chemoradiotherapy. CSPO may be an alternative choice for patients with very low rectal cancers in better physical health and with higher requirements for anal function and quality of life.

[Observation on the clinical outcomes of continued pregnancy following cesarean scar pregnancy in 55 women].

Objective: To observe the clinical outcomes of continued pregnancy in pregnant women with cesarean scar pregnancy (CSP). Methods: A retrospective analysis was performed on the pregnancy outcomes of 55 pregnant women who were diagnosed with CSP at the Second Affiliated Hospital of Army Medical University during the first trimester of pregnancy from August 1st, 2018 to October 31st, 2021 and strongly requested to continue the pregnancy. Results: Of the 55 pregnant women, 15 terminated the pregnancy in the first trimester, 1 underwent hysterotomy at 23 weeks of gestation due to cervical dilation, and 39 (71%, 39/55) continued pregnancy to the third trimester achieving live births via cesarean section. The gestational age of the 39 pregnant women delivered by cesarean section was 35+6 weeks (range: 28+5-39+2 weeks), of whom 7 cases at 28+5-33+6 weeks, 20 cases at 34-36+6 weeks, and 12 cases at 37-39+2 weeks. The results of pathological examination were normal placenta in 3 cases (8%, 3/39), placenta creta in 4 cases (10%, 4/39), placenta increta in 9 cases (23%, 9/39) and placenta percreta in 23 cases (59%, 23/39). Among the 36 pregnant women who were pathologically confirmed as placenta accreta spectrum disorders (PAS) after surgery, the last prenatal ultrasonography showed placenta previa in 27 cases (75%, 27/36) and not observed placenta previa in 9 cases. The median intraoperative blood loss, autologous blood transfusion, and allogeneic suspended red blood cell infusion of 39 pregnant women during cesarean section were 1 000 ml (300-3 500 ml), 300 ml (0-2 000 ml) and 400 ml (0-2 400 ml), respectively. The uterine preservation rate was 100% (39/39), and only 1 case received cystostomy due to intracystic hemorrhage. The birth weight of the newborn was 2 580 g (1 350-3 800 g), and 1 case of mild asphyxia. Conclusions: Pregnant women with CSP who continue pregnancy under close monitoring after adequate ultrasound evaluation and doctor-patient communication could achieve better maternal and infant outcomes, but pregnant women with CSP are highly likely to continue pregnancy and develop into PAS. Effective hemostasis means and multidisciplinary team cooperation are needed in perinatal period for ensuring maternal and fetal safety.

[Association of sleep duration and risk of frailty among the elderly over 80 years old in China: a prospective cohort study].

Objective: To explore the association between sleep duration and the risk of frailty among the elderly over 80 years old in China. Methods: Using the data from five surveys of the China Elderly Health Influencing Factors Follow-up Survey (CLHLS) (2005, 2008-2009, 2011-2012, 2014, and 2017-2018), 7 024 elderly people aged 80 years and above were selected as the study subjects. Questionnaires and physical examinations were used to collect information on sleep time, general demographic characteristics, functional status, physical signs, and illness. The frailty state was evaluated based on a frailty index that included 39 variables. The Cox proportional risk regression model was used to analyze the correlation between sleep time and the risk of frailty occurrence. A restricted cubic spline function was used to analyze the dose-response relationship between sleep time and the risk of frailty occurrence. The likelihood ratio test was used to analyze the interaction between age, gender, sleep quality, cognitive impairment, and sleep duration. Results: The age M (Q1, Q3) of 7 024 subjects was 87 (82, 92) years old, with a total of 3 435 (48.9%) patients experiencing frailty. The results of restricted cubic spline function analysis showed that there was an approximate U-shaped relationship between sleep time and the risk of frailty. When sleep time was 6.5-8.5 hours, the elderly had the lowest risk of frailty; Multivariate Cox proportional risk regression model analysis showed that compared to 6.5-8.5 hours of sleep, long sleep duration (>8.5 hours) increased the risk of frailty by 13% (HR: 1.13; 95%CI: 1.04-1.22). Conclusion: There is a nonlinear association between sleep time and the risk of frailty in the elderly.

[Evaluation of the performance of InnowaveDX MTB/RIF for the detection of Mycobacterium tuberculosis complex and rifampicin resistance].

Objective: To evaluate the performance of Mycobacterium tuberculosis and rifampicin resistance mutation detection kit (InnowaveDX MTB/RIF, referred to as "InnowaveDX") in diagnosing tuberculosis and rifampicin resistance using sputum samples. Methods: From June 19, 2020 to May 16, 2022, patients with suspected tuberculosis were prospectively and consecutively enrolled in Hunan Provincial Tuberculosis Prevention and Control Institute, Henan Provincial Hospital of Infectious Diseases and Wuhan Jinyintan Hospital. A total of 1 328 patients with suspected tuberculosis were finally included. According to the inclusion and exclusion criteria, 1 035 pulmonary tuberculosis patients (357 were confirmed tuberculosis cases and 678 were clinically diagnosed tuberculosis cases) and 180 non-tuberculosis patients were finally included. Sputum samples were collected from all patients for routine sputum smear acid-fastness tests, mycobacterial culture and drug susceptibility testing. Moreover, the diagnostic value of Xpert®MTB/RIF (referred to as "Xpert") and InnowaveDXin detecting tuberculosis and rifampicin resistance was evaluated. Clinical diagnosis and culture results of Mycobacterium tuberculosis were used as reference standards to assess tuberculosis diagnosis, and phenotypic drug sensitivity and Xpert were used as reference standards to assess rifampicin resistance. The sensitivity, specificity, positive predictive value and negative predictive value of the two methods for tuberculosis diagnosis and rifampicin resistance were analyzed. The consistency of the two techniques was analyzed usingkappa test. Results: Taking clinical diagnosis as the reference standard, the detection sensitivity of InnowaveDX [58.0% (600/1 035)] was higher than that of Xpert [51.7% (535/1 035)] in 1035 patients with pulmonary tuberculosis, and the difference was statistically significant (P<0.001). In 270 pulmonary tuberculosis patients with culture-positive pulmonary tuberculosis identified as M.tuberculosis-complex, the positive rates of InnowaveDX and Xpert were both high [99.6%(269/270)and 98.2%(265/270), respectively] and there was no statistical difference. In culture-negative patients with pulmonary tuberculosis, the sensitivity of InnowaveDX was 38.8% (198/511), which was higher than that of Xpert (29.4%, 150/511), and the difference was statistically significant (P<0.001). Taking phenotypic drug-susceptibility testing (DST) as reference, the sensitivity of InnowaveDX to rifampicin resistance was 99.0% (95%CI: 94.7%-100.0%) and the specificity was 94.0%(95%CI: 88.5%-97.4%). With Xpert as the reference, the sensitivity and specificity of InnowaveDX were 97.1% (95%CI: 93.4%-99.1%) and 99.7% (95%CI: 98.4%-100.0%), respectively, and the kappa value was 0.97 (P<0.001). Conclusions: InnowaveDX show a high sensitivity for detecting Mycobacterium tuberculosis, especially in pulmonary tuberculosis patients with a clinical diagnosis and negative culture results. It also showed high sensitivity in detecting rifampicin resistance with DST and Xpert as reference respectively. InnowaveDX is an early and accurate diagnostic tool for TB and drug-resistant TB, particularly suitable for application in low- and middle-income countries.

[The efficacy and safety of nerve loop blocking in the treatment of blepharospasm in Meige syndrome].

Objective: To evaluate the efficacy and safety of nerve loop blocking in the treatment of blepharospasm caused by Meige syndrome. Methods: It was a retrospective case series study. Patients with Meige syndrome characterized by blepharospasm or blepharospasm-oromandibular dystonia who underwent nerve loop blocking in the Ophthalmology Department of Henan No. 3 Provincial People's Hospital from April 2018 to January 2020 were included. Before and after surgery, blepharospasm was graded, and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) was used to score the symptoms of ocular and oral dystonia. The improvement rate of ocular spasm was calculated after surgery according to the scores. The postoperative complications were observed. The Wilcoxon rank test was used to compare the BFMDRS movement subscale scores before and after surgery. The independent sample Mann-Whitney U test was used to compare the improvement rates of eye spasm between male and female patients and between patients with and without combined oromandibular dystonia. Results: Among the 199 patients included, 64 (32.2%) were males, and 135 (67.8%) were females, aged 58 (51, 64) years (22-79 years). The postoperative follow-up period was 24 (21, 28) months. Preoperatively, blepharospasm was graded as grade 3 in 12 patients (6.0%) and grade 4 in 187 patients (94.0%), while the postoperative blepharospasm grades were grade 0 in 100 patients (50.3%), grade 1 in 64 patients (32.2%), grade 2 in 31 patients (15.6%), and grade 3 in 4 patients (2.0%). There was statistically significant difference in the BFMDRS scores of ocular dystonia before and after surgery [8.0 (8.0, 8.0) vs. 0.0 (0.0, 1.0); Z=-12.41, P<0.001]. The improvement rate of blepharospasm in all patients was 100% (87.5%, 100%), ranging from 43.8% to 100%, with no statistically significant difference between patients of different genders and between patients with and without combined oral dystonia (both P>0.05). Statistically significant difference existed in the scores of oral dystonia before and after surgery [2.0 (0.5, 4.5) vs. 1.0 (0.5, 2.0); Z=-4.38, P<0.001], with 25 of 65 patients (38.5%) having their oral symptoms improved. Postoperative complications included eyelid valgus (7.5%, 15/199), frontal numbness (100%, 199/199) and tearing (89.9%, 179/199). Conclusion: Nerve loop blocking is a relatively safe and effective method in the treatment of blepharospasm symptoms of Meige syndrome.

Preoperative MRI of breast squamous cell carcinoma: diagnostic value of distinguishing between two subtypes.

AIM: To retrospectively analyse the clinical and MRI data of primary squamous cell carcinoma (SCC), particularly pure squamous cell carcinoma (PSCC) and mixed squamous cell carcinoma (MSCC). MATERIALS AND METHODS: The MRI data and clinicopathological characteristics of 20 patients with histopathologically confirmed SCC of the breast, including eight PSCC patients and 12 MSCC patients, from multiple centres between January 2013 and December 2020 were analysed retrospectively. RESULTS: Nine of 12 patients in the MSCC group showed hyperintensity on T1-weighted imaging (WI), while this feature was not observed in the PSCC group (p=0.001). Most of the PSCC group showed rim enhancement, whereas most of the MSCC group showed heterogeneous enhancement (p=0.007). In addition, there was no significant difference in the thickness of the rim enhancement and the percentage of necrotic components in the tumours between the two types of SCCs of the breast (p=0.545 and p=0.662, respectively). Four patients (4/12) in the MSCC group had sentinel lymph node metastasis, while only one patient (1/8) in the PSCC group showed lymph node metastasis (p=0.603). Metastatic disease occurred in 25% of patients with PSCC and in approximately 41.7% of patients with MSCC. CONCLUSION: The signal on T1WI and internal enhancement characteristics were the key features for differentiating PSCC and MSCC. Therefore, MRI phenotypes may provide additional information for the pathological classification of breast SCC.

Ontogenetic characteristics of the intestinal microbiota of Quasipaa spinosa revealed by 16S rRNA gene sequencing.

To analyse the correlation between the intestinal microbiota (IM) and differential development of Quasipaa spinosa across different stages of metamorphosis, we focused on four key developmental periods (15 days post-hatch [dph; Gosner stage, GS23], 60 dph [GS25], 90 dph [GS41] and 150 dph [GS25, GS41, GS42, GS46]) and used 16S rDNA amplicon sequencing. Results showed that IM diversity in Q. spinosa was related to life history. Specifically, there was a significant difference between the aquatic and terrestrial stages, and IM diversity increased with age. Proteobacteria, Bacteroidetes and Firmicutes were the dominant phyla in tadpoles, whereas Bacteroidetes, Proteobacteria, Firmicutes and Fusobacteria were the dominant phyla at the metamorphosis stages. The composition of the IM at different stages and ages varied considerably, but the changes were not substantial among different development stages at 150 dph. This was probably because age has a greater influence than growth factors, and host selective pressure increases with age. This study provides a theoretical reference for subsequent studies on the IM, as well as for the prevention of amphibian endogenous pathogenic microbial diseases.

[The value of ischemia modified albumin level for predicting in-hospital mortality in patients with acute aortic dissection].

Objective: To investigate the value of ischemia modified albumin (IMA) level for predicting in-hospital mortality in patients with acute aortic dissection (AAD). Methods: A total of 195 patients with AAD from the Department of Cardio-Vascular Surgery of Affiliated Hospital of North Sichuan Medical College from January 2017 to November 2019 were consecutively collected, with 126 males and 69 females. Based on whether they died during hospitalization or not, these patients were divided into 2 groups: survival group and mortality group. The baseline data and IMA levels at admission of the two groups were recorded. Univariate logistic regression analysis was used to identify the independent risk factors, and multivariate logistic regression analysis was further performed on variables with statistical significance in univariate analysis. The area under the receiver operating characteristic (ROC) curve was calculated to determine the value of IMA for predicting in-hospital mortality in patients with AAD. Results: Forty-two AAD patients died and 153 survived, and the mortality rate was 21.5%. Logistic regression analysis showed that age (OR=2.143,95%CI:1.247-4.826,P=0.011), Stanford type A (OR=6.751,95%CI:3.189-14.291,P<0.001), drug therapy (OR=5.133,95%CI:2.463-10.700,P<0.001), IMA level (OR=4.452,95%CI:2.231-8.953,P=0.004) were independent risk factors for in-hospital mortality in patients with AAD, however surgery was a protective factor (OR=0.195,95%CI:0.093-0.406,P<0.001). The area under the ROC curve for IMA level in predicting in-hospital mortality with AAD was 0.838 (95%CI: 0.774-0.901, P<0.001), with a cut-off value of 86.55 U/ml, and the sensitivity and specificity were 83.3% and 75.2%, respectively. Conclusions: IMA may serve as a simple risk assessment indicator for patients with AAD. IMA level at admission is an independent predictor of in-hospital mortality. For patients with higher IMA level, early surgical intervention should be performed.