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Sinomenine (SIN) is commonly used as part of rheumatoid arthritis (RA) therapy in China, but there is still no published evidence of the efficacy of SIN monotherapy. This work investigates the efficacy and safety of SIN in treating RA patients and analyzes the correlation between ornithine level and the alleviation of disease activity in RA patients. In this 24 week, randomized, placebo-controlled, double-blind clinical trial, people with mild to moderate RA were randomly assigned (1:1:1, stratified by hospital) to receive SIN (120 mg, twice daily), methotrexate (MTX) (10 mg per week), or SIN + MTX therapy. The primary outcome was the proportion of patients who achieved a 50% improvement in the American College of Rheumatology (ACR) criteria at week 24 and who showed improvement according to the clinical disease activity index (CDAI). In this prospective subgroup analysis, we also assessed whether the 24 week alterations of disease activity in the treatment group were significantly correlated to the levels of blood ornithine. Of the 135 enrolled participants, 38, 39, and 36 patients were treated with SIN, MTX, and SIN + MTX, respectively. In the SIN-treated group, 52.63% of patients achieved ACR50 after 24 weeks of treatment, which was comparable to the results in the MTX-treated and SIN + MTX-treated groups. Hepatic and gastrointestinal disorders were the main adverse events; however, the ratio of patients suffering from hepatic disorder in the SIN group (1/38) was much lower than that in the MTX (10/39) and SIN + MTX (8/36) groups. A total of 221 serum samples were collected at the four follow-up time points in the three treatments, and the levels of ornithine, citrulline, and arginine were obtained through ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). The serum ornithine level decreased after the 24 week treatment along with a decrease in disease activity, and may reflect therapeutic responses with a sensitivity value of 80%. In conclusion, SIN revealed a comparable efficacy to MTX for treating RA patients, but with fewer side effects. In addition, the serum ornithine level was found for the first time to have a close correlation with the alleviation of RA, which shows the value of this measure as an assessment indicator of drugs in treating RA.

Objective: To explore whether there is a specific clinical effect of acupuncture in the treatment of chronic prostatitis. Methods: A total of 52 patients with chronic prostatitis were randomly divided into an acupuncture group (24 cases) and a placebo acupuncture group (28 cases). During the treatment, 1 case was dropped out in the placebo acupuncture group and 51 patients accomplished the clinical trial finally in two groups. In the acupuncture group, Shenshū (肾俞BL23), Zhōngliao (中髎BL33), Huiyang (会阳BL35) and Sānyīnjiāo (三阴交SP6) were selected. In the placebo acupuncture group, the non-meridian points located lateral to BL23, BL33, BL35 and SP6 were selected respectively. The duration of treatment was 8 weeks in each group. In the first 4 weeks of treatment, the treatment was given once every two days, three times weekly. In the last 4 weeks of treatment, the treatment was given once every three days, twice a week. Totally, 20 acupuncture treatments were required in the whole trial. Before treatment, in week 4 and 8 of treatment and in follow-up, National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) score and the comprehensive effect were evaluated in the two groups successively. Results: In week 4 and 8 of treatment, NIH-CPSI score in the acupuncture group was lower than that before treatment respectively (both P Conclusion: Acupuncture relieves pelvic pain and urination symptoms and has a certain of long-term effect in patients with chronic prostatitis.

The cT3 substage criteria based on extramural depth of tumor invasion in rectal cancer have several limitations.This study proposed that the distance between the deepest tumor invasion and mesorectal fascia on pretherapy MRI can distinguish the prognosis of patients with cT3 rectal cancer.This is a cohort study.This study included a prospective, single-center, observational cohort and a retrospective, multicenter, independent validation cohort.Patients who had cT3 rectal cancer with negative mesorectal fascia undergoing neoadjuvant chemoradiotherapy followed by radical surgery were included in 4 centers in China from January 2013 to September 2014.Baseline MRI with the distance between the deepest tumor invasion and mesorectal fascia, extramural depth of tumor invasion, and mesorectum thickness were measured.The cutoff of the distance between the deepest tumor invasion and mesorectal fascia was determined by time-dependent receiver operating characteristic curves, supported by a 5-year progression rate from the prospective cohort, and was then validated in a retrospective cohort.There were 124 and 274 patients included in the prospective and independent validation cohorts. The distance between the deepest tumor invasion and mesorectal fascia was the only predictor for cancer-specific death (HR, 0.1; 95% CI, 0.0-0.7) and was also a significant predictor for distant recurrence (HR, 0.4; 95% CI, 0.2-0.9). No statistically significant difference was observed in prognosis between patients classified as T3a/b and T3c/d.The sample size is relatively small, and the study focused on cT3 rectal cancers with a negative mesorectal fascia.A cutoff of 7 mm of the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI can distinguish cT3 rectal cancer from a different prognosis. We recommend using the distance between the deepest tumor invasion and mesorectal fascia on baseline MRI for local and systemic risk assessment and providing a tailored schedule of neoadjuvant treatment. See Video Abstract at http://links.lww.com/DCR/B682.CORRELACIÓN ENTRE LA DISTANCIA DE LA FASCIA MESORRECTAL Y EL PRONÓSTICO DEL CÁNCER DE RECTO cT3: RESULTADOS DE UN ESTUDIO MULTICÉNTRICO DE CHINAANTECEDENTES:Los criterios de subestadificación cT3 basados en la profundidad extramural de invasión tumoral en el cáncer de recto tienen varias limitaciones.OBJETIVO:Este estudio propuso que la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética preterapia puede distinguir el pronóstico de los pacientes con cT3.DISEÑO:Estudio de cohorte.ENTORNO CLINICO:El estudio incluyó una cohorte observacional, prospectiva, unicéntrica, y una cohorte de validación retrospectiva, multicéntrica e independiente.PACIENTE:Se incluyeron pacientes con cáncer de recto cT3 con fascia mesorrectal negativa sometidos a quimio-radioterapia neoadyuvante seguida de cirugía radical en cuatro centros de China desde enero de 2013 hasta septiembre de 2014.INTERVENCIÓN:Imágenes de resonancia magnética de referencia fueron medidas con la distancia entre la invasión tumoral más profunda y la fascia mesorrectal; la profundidad extramural de la invasión tumoral y el grosor del mesorrecto.PRINCIPALES MEDIDAS DE VALORACION:El límite de la distancia entre la invasión tumoral más profunda y la fascia mesorrectal se determinó mediante curvas características operativas del receptor dependientes del tiempo y se apoyó en la tasa de progresión a 5 años de la cohorte prospectiva, y luego se validó en una cohorte retrospectiva.RESULTADOS:Se incluyeron 124 y 274 pacientes en la cohorte de validación prospectiva e independiente, respectivamente. La distancia entre la invasión tumoral más profunda de la fascia mesorrectal fue el único predictor de muerte específica por cáncer (Hazard ratio: 0.1, 95% CI, 0,0-0,7); y también fue un predictor significativo de recurrencia distante Hazard ratio: 0,4, 95% CI, 0,2-0,9). No se observaron diferencias estadísticamente significativas en el pronóstico entre los pacientes clasificados como T3a/b y T3c/d.LIMITACIONES:El tamaño de la muestra es relativamente pequeño y el estudio se centró en los cánceres de recto cT3 con fascia mesorrectal negativa.CONCLUSIONES:Un límite de 7 mm de distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia puede distinguir el cáncer de recto cT3 de diferentes pronósticos. Recomendamos la distancia entre la invasión tumoral más profunda y la fascia mesorrectal en la resonancia magnética de referencia para la evaluación del riesgo local y sistémico, proporcionando un programa personalizado de tratamiento neoadyuvante. Consulte Video Resumen en http://links.lww.com/DCR/B682. (Traducción- Dr. Francisco M. Abarca-Rendon).

Purpose To assess the MRI performance in differentiating pancreatic ductal adenocarcinomas (PDACs), from solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine tumors (PNETs) using non-gaussian diffusion-weighted imaging models. Methods This was a retrospective study of patients diagnosed with PDACs (01/2015–06/2019) or with PNETs or SPNs diagnosed (01/2011–12/2019) at our hospital. The lesions were randomized 1:1 to the primary and validation cohorts. The regions of interest (ROIs) were manually drawn on each slice at DWI (b = 1500 s/mm2) from 3 T MRI. D (diffusion coefficient), D* (pseudodiffusion coefficient), f (perfusion fraction), distributed diffusion coefficient (DDC), α (diffusion heterogeneity index), mean diffusivity (MD) and mean kurtosis (MK) were obtained. The parameters with largest performance for differentiation were used to establish a diagnostic model. Results There were 148, 56, and 60 patients with PDAC, PNET, and SPN, respectively. For differentiating PDACs from SPNs, f and MK values were used to establish a diagnostic model with areas under the receiver operating characteristic curves (AUCs) of 0.92 and 0.89 in the primary and validation groups, respectively. For distinguishing PDACs from PNETs, α and MK values were used to establish a diagnostic model with AUCs of 0.87 and 0.86 in the primary and validation groups, respectively. The accuracy rate of the subjective evaluation with the assistance of non-gaussian DWI models for differentiating PDAC from SPNs and PNETs were higher than that of subjective diagnosis alone (P Conclusions The non-gaussian DWI models could assist radiologists in accurately differentiating PDACs from PNETs and SPNs.

Introduction The aim of the present study was to assess the safety profile and outcomes of a ceftazidime–avibactam (CAZ-AVI)-based regimen and compare them with those of a tigecycline (TGC)-based regimen in intensive care unit (ICU) for the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP), which is classified into hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). Methods Clinical and microbiological cure rates, 28-day survival rates, and safety evaluation findings were compared between patients treated with CAZ-AVI-based regimen and those treated with TGC-based regimen in this retrospective study. Conventional multivariate logistic regression analysis and regression adjustment analysis with propensity score (PS) were performed to control for confounding variables. Results A total of 105 cases of critically ill ICU patients with CRKP-induced HAP or VAP were included in the present study from July 2019 to September 2020; 62 patients (59%) received TGC-based regimen and 43 patients (41%) received CAZ-AVI-based regimen. The most common concomitant agent in the CAZ-AVI group and TGC group was carbapenem (44.2% versus 62.9%, P = 0.058), while only a small proportion of the study population received CAZ-AVI and TGC monotherapy (20.9% versus 6.5%, P = 0.027). The clinical and microbiological cure rates of the CAZ-AVI group were superior to those of the TGC group [51.2% versus 29.0% (P = 0.022) and 74.4% versus 33.9% (P

The neoadjuvant chemotherapy plays an important role in locally advanced gastric cancer, but its efficacy, safety profiles and clinical outcomes among different regimens still remain controversial. In this study, totally 231 eligible patients with locally advanced gastric cancer were enrolled. These patients were divided into the observation group (SOX regimen, n = 123) and control group (mFOLFOX6 regimen, n = 108) according to different chemotherapy regimens. Then, the differences in chemotherapy efficacy, adverse reactions, surgical characteristics, complications and survival condition were compared. No significant differences were observed in clinical efficacy of chemotherapy, the rate of D2 lymph node clearance, R0 resection, complications, responses of neoadjuvant chemotherapy and survival condition between two groups (P > 0.05). The incidence of abdominal pain, diarrhoea, nausea and vomiting in the observation group were significantly lower than those in the control group (16.26% vs 29.63%, χ2 = 5.893, P < 0.05; 11.38% vs 26.85%, χ2 = 9.084, P < 0.05; 35.77% vs 53.70%, χ2 = 7.499, P < 0.05). The SOX regimen and mFOLFOX6 regimen have similar chemotherapy efficacy for locally advanced gastric cancer, but SOX regimen has a lower risk of gastrointestinal adverse reactions comparing with mFOLFOX6 regimen.

Si-Yu Long,1 Le Wang,1,2 Hai-Qin Jiang,1 Ying Shi,1 Wen-Yue Zhang,1 Jing-Shu Xiong,1 Pei-Wen Sun,1,2 Yan-Qing Chen,1 You-Ming Mei,1 Chun Pan,1 Gai Ge,1 Zhen-Zhen Wang,1 Zi-Wei Wu,1 Mei-Wen Yu,1,2 Hong-Sheng Wang1– 3 1Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, People’s Republic of China; 2National Centre for Leprosy Control, China CDC, Nanjing, People’s Republic of China; 3Centre for Global Health, School of Public Health, Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Hong-Sheng Wang; Mei-Wen YuJiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, St 12 Jiangwangmiao, Nanjing, Jiangsu, 210042, People’s Republic of ChinaEmail whs33@vip.sina.com; yumeiwen@163.comBackground: Genome-wide association studies (GWASs) have identified some immune-related single-nucleotide polymorphisms (SNPs) to be associated with leprosy.Methods: This study investigated the association of 17 SNPs based on previously published GWAS studies with susceptibility to leprosy, different polar forms and immune states of leprosy in a case–control study from southwestern China, including 1344 leprosy patients and 2732 household contacts (HHCs) (1908 relatives and 824 genetically unrelated contact individuals). The differences of allele distributions were analyzed using chi-squared analysis and logistic regression.Results: After adjusting covariate factors, rs780668 and rs3764147 polymorphisms influenced susceptibilities to genetically related or unrelated leprosy contact individuals. rs142179458 was associated with onset early cases, rs73058713 A allele and rs3764147 A allele increased the risk of reversal reaction, while rs3764147 G allele had higher risk to present lepromatous leprosy and erythema nodosum leprosum.Conclusion: Our results demonstrated that genetic variants in the LACC1, HIF1A, SLC29A3 and CDH18 genes were positively correlated with the occurrence of leprosy and leprosy clinical phenotypes, providing new insights into the immunogenetics of the disease.Keywords: leprosy, association study, susceptibility gene, polymorphisms

BACKGROUND Advance care planning (ACP) is low among older adults with cancer. In a secondary analysis of randomized trial data, the authors compared the efficacy of the PREPARE for Your Care (PREPARE) website plus an easy-to-read advance directive (AD) with an AD only among older adults with and without cancer. METHODS Safety net, primary care patients in San Francisco were included if they were 55 years old or older, were English- or Spanish-speaking, and had 2 or more chronic conditions. The authors determined cancer diagnoses by using International Classification of Diseases, Ninth Revision/Tenth Revision codes. The primary outcome was new ACP documentation in the medical record at 15 months; the secondary outcomes were self-reported ACP engagement, ease of use, satisfaction, and depression/anxiety. The authors used mixed effects logistic and linear regression adjusted for prior ACP, health literacy, and clinician, including a cancer interaction term. RESULTS Of 986 participants, 220 (22%) had cancer. The mean age was 63 years (SD, 6 years), 61% were women, 81% were of a minority race/ethnicity, 45% were Spanish-speaking, 39% had limited health literacy, and 27% had prior ACP. New ACP documentation was higher in the PREPARE arm versus the AD-only arm among participants with cancer (62% vs 43%; P = .01) and without cancer (38% vs 28%; P = .01), as was ACP engagement in both arms (P < .001), with no interactions by cancer. Ease of use and satisfaction were high, and depression/anxiety was low, with no differences by study arm or by cancer/no cancer. CONCLUSIONS PREPARE plus an easy-to-read AD increased ACP documentation and engagement among diverse older adults with cancer more than an AD alone, with no increase in depression or anxiety between study arms or by cancer. PREPARE may help to decrease ACP disparities among patients with cancer. LAY SUMMARY Advance care planning (ACP) is the process of sharing values, goals, and preferences for medical care, but engagement in ACP is low among older adults with cancer. Among 986 English- and Spanish-speaking older adults from a safety net hospital, an interactive, multimedia, web-based ACP program (PREPARE for Your Care at https://prepareforyourcare.org/) plus an easy-to-read advance directive increased ACP documentation and engagement more than an advance directive alone. There were no differences in this increase in ACP between older adults with cancer and older adults without cancer. Also, engaging in ACP did not result in increased depression or anxiety.

Background: Secondary hypertension has emerged as a major public health problem in China. Early diagnosis and treatment can significantly improve the clinical outcomes. However, data on the current cause composition in China are seldom reported. Objective: To describe the trends in cause-related comorbidities in hospitalized patients with secondary hypertension in China from 2013 to 2016. Methods: This was a retrospective analysis based on the national Hospital Quality Monitoring System (HQMS) database, which collects information from the front pages of in-hospital medical records. Hospitalized patients with secondary hypertension from 746 tertiary hospitals that consistently uploaded data to the HQMS from 2013 to 2016 were enrolled. All diagnoses were identified using International Classification of Diseases version 10 (ICD-10) diagnostic codes. Descriptive analyses were used to determine the proportions of secondary hypertension causes and changing trends over 4 years. Result: The study collected data on 402 371 hospitalized patients with secondary hypertension from the HQMS during 2013–2016. Secondary hypertension caused by renal parenchymal disease ranked first and accounted for more than 50%. Obstructive sleep apnea syndrome (OSAS) followed closely with a rate of approximately 25%. Primary aldosteronism presented the highest proportion among all causes of endocrine hypertension. Regarding longitudinal changes over time, the rates of renal hypertension showed a significant downward trend from 2013 to 2016 (P

Background The main purpose was to determine basic epidemiological data on CKD among hospitalized pediatric patients in China. Methods Data from pediatric inpatients with CKD hospitalized from June 1, 2013 to May 31, 2017 were extracted from the electronic records of HQMS database, which includes over 14 million inpatients. Codes from the 10th revision of the International Classification of Diseases (ICD-10) were used to search the database. Results A total of 524 primary diseases of CKD were included in this study. In all, there were 278 231 pediatric inpatients with CKD, which accounted for 1.95 % of the 14 250 594 pediatric inpatients registered in the HQMS database. The number of pediatric inpatients with CKD was 67 498 in 2013, 76 810 in 2014, 81 665 in 2015 and 82 649 in 2016, which accounted for 1.93 %, 1.93 %, 1.99 and 2.09 %, respectively, of the total population of pediatric inpatients. The etiology of CKD was secondary nephrosis in 37.95 % of cases, which ranked first and followed by CAKUT with a percentage of 24.61 %. Glomerular diseases and cystic kidney disease accounted for 21.18 and 5.07 %, respectively. Among all 278 231 patients, 6 581 (2.37 %) had a primary discharge diagnosis of CKD. The renal pathology findings of CKD showed that IgA accounted for 51.17 %. Conclusions This study provides a descriptive analysis of the hospitalized population of pediatric CKD patients. Our study provides important, fundamental data for policy making and legislation, registry implementation and the diagnosis, treatment and prevention of CKD in China.

Purpose To describe the supportive care needs of Chinese women newly diagnosed with breast cancer prior to adjuvant chemotherapy. Participants & setting 13 women newly diagnosed with breast cancer were recruited from a public teaching hospital in northern China. Methodologic approach Semistructured interviews were conducted, and data were analyzed following a qualitative descriptive approach and qualitative content analysis. Findings The following five themes emerged. Implications for nursing Nurses should focus on patients' prechemotherapy supportive care needs and comprehensively assess their specific needs and concerns related to post-surgery discomfort and chemotherapy, with considerations of the Chinese family concept, diet, and traditional culture. Targeted health information and psychological support are necessary to help patients transition to and adequately prepare for chemotherapy.

BACKGROUND Several previous studies have reported an unusual root formation in which a fractured apical fragment of an immature root continued to develop independent of the main root after trauma to an immature tooth. To date, there have been only rare reports of the continuing apical formation of the fractured root associated with dens evaginatus (DE). This paper presents a case of a separated root tip formation associated with a fractured tubercle of DE. CASE SUMMARY An 11-year-old boy was referred for gingival sinus on the buccal side of the right mandibular second premolar (tooth # 45). Clinically, tooth # 45 was free of caries, but there was a sign of a fractured tubercle of DE on the occlusal surface. Radiography showed that the root canal of tooth # 45 was widely radiolucent. A separated root apex was found apically under the main root and was nearly completely formed with an apical orifice at the apical tip. Tooth # 45 was diagnosed as tubular fracture of DE with chronic apical periodontitis. A revascularization technique was recommended to treat the tooth. At 3-mo and 1-yr follow-up, the patient remained asymptomatic. Periapical radiography revealed that the separated root tip distally drifted with closure of the apex. However, the root length and thickness of the main root did not increased. CONCLUSION Clinicians should be aware that even if tubercle of DE is fractured in an immature tooth, the root tip may be separated from the main root and completely formed.

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide. Our previous studies have found that traditional Chinese medicine, Panax notoginseng (P. notoginseng) can reduce cerebral hemorrhage in rats with TBI. Yet, the exact mechanism still remains unclear. According to the random number table, 36 SD rats were randomly divided into six groups: Sham group (negative control group), Model group, PIK inhibitor group (positive group), P. notoginseng group (experimental group), Rapamycin group, and Panax notoginseng+Rapamycin group (experimental group). In the Model group (M group, the group showing signs of TBI without any treatment), the neural function defect score was significantly decreased, while sequestosome 1 (P62), Beclin 1, and microtubule-associated protein 1 light chain 3 (LC3-II) were significantly increased. The brain tissue was significantly damaged, and many autophagosomes were observed in the cytoplasm. Compared with the Model group and the Rapamycin group (M+Rapa group, the group showing signs of TBI with Rapamycin treatment), P62, Beclin 1, and LC3-II were significantly decreased, the score of neural function defect was significantly improved, and the brain tissue damage was significantly reduced in the PIK (phosphatidylinositol 3-kinase) inhibitor group (M+LY group, the group showing signs of TBI with PIK inhibitor treatment). Compared with the Model group, mTOR was decreased and LC3-II was increased; however, there were no significant changes in neural function defect score, HE staining, Nissl staining, and transmission electron microscopy in the Rapamycin group. Compared with the Model group, the neural function defect score at 72h was significantly improved, mTOR was significantly increased, P62, Beclin 1, and LC3-II significantly decreased, brain tissue damage was reduced in HE staining and Nissl staining, autophagosomes were reduced in cytoplasm by transmission electron microscopy in the P. notoginseng group (M+PN group, the group showing signs of TBI with P. notoginseng treatment). Also, there was no significant difference between P. notoginseng group and P. notoginseng+Rapamycin group (M+PN+Rapa group, the group showing signs of TBI with P. notoginseng+Rapamycin treatment). P. notoginseng protects the rat brain function from TBI by inhibiting autophagy through the mTOR signaling pathway and other autophagy pathways.

We aimed to analyse the reasons behind the need for cochlear implant revision surgeries, as well as the rate at which they occur, to reduce the revision surgery rate for non-device failures. We also aimed to elucidate the cumulative survival and device survival rates in different age groups. This retrospective single cohort study reviewed 4563 cochlear implant surgeries and 119 revision surgeries performed at a tertiary referral hospital in China between 1996 and 2019. Kaplan–Meier curves were used to calculate the cumulative survival and device survival rates. The revision surgery rate was 2.61%. The reasons for revision included device (73.1%) and non-device (26.9%) failures. The most common reasons were hard device (47.1%) and non-device failure (28.6%). The 10- and 20-year cumulative survival rates were 96.8% and 96.7%, respectively. Younger children were more likely to undergo a second surgery. This study is the longest study about revision surgery in China. Cochlear implantation is a reliable treatment. It has a low complication rate in patients with sensorineural hearing loss. Children have a higher revision rate than adults. Doctors should be aware of each complication and perform the appropriate procedure.

Treatment of patients with triple-negative breast cancer (TNBC) has been challenging due to a lack of well-defined molecular targets. The Wnt/β-catenin pathway is known to be activated in many TNBC patients and BCL9 and BCL9L are important transcriptional co-activators of β-catenin, but whether inhibition of BCL9/BCL9L can suppress TNBC growth and the underlying mechanism are not fully understood. Here we demonstrate that the expression of BCL9 and BCL9L is directly correlated with malignancy in TNBC patient tumors and that BCL9 and BCL9L promote tumor cell growth, cell migration and metastasis in TNBC models. Mechanistically, we found that BCL9/BCL9L promotes tumorigenicity through both the Wnt and TGF-β pathways. Besides, BCL9/BCL9L expression inversely correlates with CD8+ T cell infiltration in TNBC and BCL9/BCL9L inhibits the infiltration of CD8+ T cells in the tumor microenvironment. hsBCL9CT-24, an inhibitor of BCL9/β-catenin peptides, promotes intratumoral infiltration of cytotoxic T cells, reducing regulatory T cells (Treg) and increasing dendritic cells (DCs). Inhibition of BCL9/BCL9L and TGF-β suppresses activity of Treg. TGF-β signaling increases tumor infiltration of cytotoxic CD8+ T cells. In accordance, genetic or pharmacological inhibition of BCL9/BCL9L synergizes with PD-1/L1 antibodies to inhibit tumor growth. In summary, these results suggest that targeting BCL9/BCL9L has a direct anti-tumor effect and also unleashes an anti-cancer immune response through inhibition of both Wnt and TGF-β signaling, suggesting a viable therapeutic approach for TNBC treatment.

Hepatitis viruses are chief pathogens of hepatitis and end-stage liver diseases. Their replication and related pathogenic process highly rely on the host micro-environment and multiple cellular elements, including exosomes. Representing with a sort of cell-derived vesicle structure, exosomes were considered to be dispensable cellular components, even wastes. Along with advancing investigation, a specific profile of exosome in driving hepatitis viruses’ infection and hepatic disease progression is revealed. Exosomes greatly affect the pathogenesis of hepatitis viruses by mediating their replication and modulating the host immune responses. The characteristics of host exosomes are markedly changed after infection with hepatitis viruses. Exosomes released from hepatitis virus-infected cells can carry viral nucleic or protein components, thereby acting as an effective subterfuge for hepatitis viruses by participating in viral transportation and immune escape. On the contrary, immune cell-derived exosomes contribute toward the innate antiviral immune defense and virus eradication. There is growing evidence supporting the application of exosomal biomarkers for predicting disease progress or therapeutic outcome, while exosomal nanoshuttles are regarded as promising therapeutic options based on their delivery properties and immune compatibility. In this review, we summarize the biogenesis and secretion mechanism of exosomes, review the recent findings pertaining to the role of exosomes in the interplay between hepatitis viruses and innate immune responses, and conclude their potential in further therapeutic application.

Yuying Shi,1– 3,* Mengyuan Dai,1– 3,* Yaxing Zhang,1– 3 Yuwen Qi,1– 3 Zhen Li,1– 3 Hongbing Cai1– 3 1Department of Gynecological Oncology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Tumor Biological Behaviors, Wuhan, Hubei, People’s Republic of China; 3Hubei Cancer Clinical Study Center, Wuhan, Hubei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hongbing CaiZhongnan Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of ChinaTel +86-1-339-716-8990Email chb21051@163.comIntroduction: Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian cancer characterized by highly aggressive and poor prognosis. However, it is unclear what factors are associated with OCCC recurrence and death. The study aimed to evaluate whether residual tumor diameter after primary debulking surgery, or other clinicopathological features play roles in predicting survival outcome in stage II–IV OCCC patients.Material and Methods: We present a retrospective study of OCCC patients with stage II–IV in our department from 2010 to 2015. Kaplan–Meier method was used to draw a survival curve. Survival analysis was performed using Log-rank test for univariate analysis and COX proportional risk regression model for multivariate analysis.Results: In this cohort of 78 patients who underwent primary debulking surgery, 47 patients had disease recurrence and 32 cases died. On univariate analysis, FIGO stage, residual tumor diameter and ascites were significant predictors of 3-year PFS (P values< 0.05) and OS (P values< 0.05). On multivariate analysis, the residual tumor diameter was an independent prognostic factor for 3-year PFS and OS (P values< 0.05). The outcomes of patients in residual-free group were significantly better than those in the residual tumor diameter 0– 1cm and > 1cm group (PFS: P=0.000, OS: P=0.001), but there was no significant difference in prognosis between 0– 1cm and > 1cm group (P values > 0.05). Greater residual tumor diameter predicted progression on cox analysis in patients with stage III, but not for patients with stage IV.Conclusion: Residual tumor diameter is prognostic after surgery for OCCC. Achieving no residual disease will significantly improve the prognosis inadvanced OCCC patients.Keywords: ovarian clear cell carcinoma, residual tumor diameter, progression

To explore which computed tomography (CT) features can predict pathological complete response (pCR) (ypT0N0) after neoadjuvant chemotherapy (NAC) in patients with gastric adenocarcinoma (GC). This study reviewed an institutional database of patients who underwent resection of GC after NAC and identified patients with pCR from January 2010 to December 2013. The correlations between pre-chemotherapy and post-chemotherapy CT features and pCR were analyzed. Eleven of 199 patients with GC who achieved ypT0N0 status after NAC were classified as the pCR group in this study. After matching pCR (n = 11) and non-pCR patients (n = 44) in the ratio of 1:4, a total of 55 cases were analyzed. The binary logistic regression analysis showed that the post-chemotherapy short diameter of the largest lymph node and tumor thickness ratio reduction were independent predictors of pCR, with an area under the curve (AUC) of 0.94 on the receiver operating characteristic (ROC) curve analysis. Two CT features, including the short diameter of the largest lymph node post-chemotherapy and tumor thickness ratio reduction, are good predictors of pCR after NAC in patients with GC.

Charcot-Marie-Tooth disease (CMT) represents a phenotypically and genetically heterogeneous disorder of the peripheral nervous system. Biallelic variants in SLC12A6 have been reported as the cause of autosomal-recessive (AR) hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC). Here we identified an autosomal-dominant (AD) heterozygous mutation in SLC12A6 in a Chinese patient with intermediate CMT. The patient presented with slowly progressive distal muscle weakness and atrophy. Electrophysiological examination showed a mixed axonal/demyelinating neuropathy. Cognition and brain MRI were normal. A single heterozygous missense mutation c.620G>A (p.R207H) in exon 5 of SLC12A6 was identified as the likely pathogenic mutation by whole-exome sequencing consistent with two previously published cases. It affects evolutionarily highly conserved amino acid residue and is predicted to be deleterious by using in silico tools. Modelling of the mutant KCC3 cotransporter showed altered formation of hydrogen bonds and weakened interaction force between the mutated site and its surrounding amino acid residues. Our findings expand the genotypic and phenotypic spectrum associated with SLC12A6 mutations from AR-HMSN/ACC to AD-CMT. The differences in the inheritance pattern might be associated with a dominant-negative pathomechanism.

Fufang Danshen preparation (FDP) is consisted of Salviae Miltiorrhizar Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi) and Borneolum Syntheticum (borneol). FDP is usually used to treat myocardial ischemia hypoxia, cerebral ischemia and alzheimer's disease, etc. In the treatment of cerebrovascular diseases, borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs, especially to the brain. The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA (TS IIA), salvianolic acid B (SAB) and ginsenoside Rg1 in FDP. Male healthy Sprague-Dawley (SD) rats were given Danshen extracts, Sanqi extracts (Panax notoginsengsaponins) or simultaneously administered Danshenextracts, Sanqi extracts and borneol. Plasma and brain samples were collected at different points in time. The concentration of TS IIA, SAB and Rg1 was determined by UPLC-MS/MS method. The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software. In comparison with Danshen and Sanqi alone, there were significant differences in pharmacokinetic parameters of TS IIA, SAB and Rg1, and the brain distribution of SAB and TS IIA when Danshen, Sanqi and borneol were administrated together. Borneol statistically significant shortened tmax of TS IIA, SAB and Rg1 in plasma and brain, increased the bioavaiability of Rg1, inhibited metabolism of Rg1 and enhanced the transport of TS IIA and SAB to brain. These results indicated that borneol could affect the multiple targets components and produce synergistic effects. Through accelerating the intestinal absorption and brain distribution, borneol caused the effective ingredients of Danshen and Sanqi to play a quicker therapeutic role and improved the therapeutic effect.

Objectives We investigated the value of radiomics data, extracted from pretreatment computed tomography images of the primary tumor (PT) and lymph node (LN) for predicting LN metastasis in esophageal squamous cell carcinoma (ESCC) patients. Materials and methods A total 338 ESCC patients were retrospectively assessed. Primary tumor, the largest short-axis diameter LN (LSLN), and PT and LSLN interaction term (IT) radiomic features were calculated. Subsequently, the radiomic signature was combined with clinical risk factors in multivariable logistic regression analysis to build various clinical-radiomic models. Model performance was evaluated with respect to the fit, overall performance, differentiation, and calibration. Results A clinical-radiomic model, which combined clinical and PT-LSLN-IT radiomic signature, showed favorable discrimination and calibration. The area under curve value was 0.865 and 0.841 in training and test set. Conclusions A venous computed tomography radiomic model based on the PT, LSLN, and IT radiomic features represents a novel noninvasive tool for prediction LN metastasis in ESCC.

Objective To forward the magnetic resonance imaging (MRI) based distance between the deepest tumor invasion and mesorectal fascia (DMRF), and to explore its prognosis differentiation value in cT3 stage rectal cancer with comparison of cT3 substage. Methods This was a retrospective, multicenter cohort study including cT3 rectal cancer patients undergoing neoadjuvant chemoradiotherapy followed by radical surgery from January 2013 to September 2014. DMRF and cT3 substage were evaluated from baseline MRI. The cutoff of DMRF was determined by disease progression. Multivariate cox regression was used to test the prognostic values of baseline variables. Results A total of 804 patients were included, of which 226 (28.1%) developed progression. A DMRF cutoff of 7 mm was chosen. DMRF category, the clock position of the deepest position of tumor invasion (CDTI) and extramural venous invasion (EMVI) were independent predictors for disease progression, and hazard ratios (HRs) were 0.26 [95% confidence interval (95% CI), 0.13−0.56], 1.88 (95% CI, 1.33−2.65) and 1.57 (95% CI, 1.13−2.18), respectively. cT3 substage was not a predictor for disease progression. Conclusions The measurement of DMRF value on baseline MRI can better distinguish cT3 rectal cancer prognosis rather than cT3 substage, and was recommended in clinical evaluation.

Glioblastoma multiforme (GBM) is characterized by diffuse infiltration of the brain, active regional recurrence, low cure proportion, and limited chemotherapy efficiency. MutS homolog 6 (MSH6) is a component of the mismatch repair system related to the oncogenesis, tumor evolution, and recurrence of GBM. The impact of MSH6 upregulation on the tumor microenvironment (TME) of GBM and the feasibility of MSH6 as a potential target to improve the prognosis remain unknown. The expression of MSH6 at mRNA level indicated that MSH6 expressed higher in GBM tissues than that in normal ones. The transwell assay and expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) suggested that the capability of invasion and migration in U251-MSH6 was more stubborn. The intracranial tumor model was established with nude mice to further explore in vivo. The time-weight curve, overall survival, tumor volumes, expression levels of MMP-2 and MMP-9 in tissue, and hematoxylin and eosin staining all indicated that MSH6 had a positive effect on metastasis. The expression levels of related proteins suggested that the hypoxia TME induced by MSH6 may promote metastasis via epithelial to mesenchymal transition, stemness, and angiogenesis progress. MSH6 is an overexpressed oncogene in human GBM tissues, which accelerated metastasis by regulating hypoxia inducible factor-1A (HIF1A) to form a hypoxic TME in GBM. The MSH6 was a vital marker of GBM, making it a promising therapeutic target.

BackgroundLarge-scale real-world data to evaluate the impact of chest pain centre (CPC) accreditation on acute coronary syndrome (ACS) emergency care in heavy-burden developing countries like China are rare.MethodsThis study is a retrospective study based on data from the Hospital Quality Monitoring System (HQMS) database. This study included emergency patients admitted with ACS to hospitals that uploaded clinical data continuously to the database from 2013 to 2016. Propensity score matching was used to compare hospitals with and without CPC accreditation during this period. A longitudinal self-contrast comparison design with mixed-effects models was used to compare management of ACS before and after accreditation.ResultsA total of 798 008 patients with ACS from 746 hospitals were included in the analysis. After matching admission date, hospital levels and types and adjusting for possible covariates, patients with ACS admitted to accredited CPCs had lower in-hospital mortality (OR=0.70, 95% CI 0.53 to 0.93), shorter length of stay (LOS; adjusted multiplicative effect=0.89, 95% CI 0.84 to 0.94) and more percutaneous coronary intervention (PCI) procedures (OR=3.53, 95% CI 2.20 to 5.66) than patients admitted in hospitals without applying for CPC accreditation. Furthermore, when compared with the ‘before accreditation’ group only in accredited CPCs, the in-hospital mortality and LOS decreased and the usage of PCI were increased in both ‘accreditation’ (for in-hospital mortality: OR=0.86, 95% CI 0.79 to 0.93; for LOS: 0.94, 95% CI 0.93 to 0.95; for PCI: OR=1.22, 95% CI 1.18 to 1.26) and ‘after accreditation’ groups (for in-hospital mortality: OR=0.90, 95% CI 0.84 to 0.97; for LOS: 0.89, 95% CI 0.89 to 0.90; for PCI: OR=1.36, 95% CI 1.33 to 1.39). The significant benefits of decreased in-hospital mortality, reduced LOS and increased PCI usage were also observed for patients with acute myocardial infarction.ConclusionsCPC accreditation is associated with better management and in-hospital clinical outcomes of patients with ACS. CPC establishment and accreditation should be promoted and implemented in countries with high levels of ACS.

Nitidine chloride (NC) possesses anticancer properties in various types of human malignancies. However, the effects of NC on lung cancer cells have not been elucidated. Moreover, the molecular mechanism of NC-involved antitumor activity is unclear. Therefore, we aimed to determine the biological effect of NC and the underlying molecular insights in lung cancer cells. The antineoplastic function of NC was assessed by MTT assays, Annexin V-FITC/PI apoptosis assay, wound healing analysis, and Transwell chamber migration and invasion assay in lung cancer cells. NEDD4 modulation was evaluated by western blotting assays of lung cancer cells after NC treatments. NEDD4 overexpression and downregulation were employed to validate the critical role of NEDD4 in the NC-mediated tumor suppressive effects. We found that NC suppressed cell viability, migration and invasion, but induced apoptosis in lung cancer cells. Mechanistic exploration revealed that NC exhibited its antitumor effects by reducing NEDD4 expression. Furthermore, our rescue experiments dissected that overexpression of NEDD4 abrogated the NC-mediated antineoplastic effects in lung cancer cells. Consistently, downregulation of NEDD4 enhanced the NC-induced anticancer effects. Thus, NC is a promising antitumor agent in lung cancer, indicating that NC might have potential therapeutic applications in the treatment of lung cancer.

BACKGROUND Cutaneous metastases originating from pancreatic cancer are relatively rare. The most common reported site of metastasis is the umbilicus, and this manifestation is known as the Sister Mary Joseph’s nodule. Non-umbilical cutaneous metastases are far less common, with only a few cases reported in the literature. Our case is the first case report, to our knowledge, on metastasis involving the labia majora and flat papules. CASE SUMMARY A 49-year-old Chinese female patient presented with a number of red, swollen papules on the vulva for 2 mo. Histological examination of the labia majora lesion revealed metastatic adenocarcinoma. The serum levels of tumor biomarkers CA199, CA242, and CA125 were significantly elevated. B-mode ultrasound-guided needle biopsy of the pancreas demonstrated moderately and poorly differentiated adenocarcinoma. The patient finally declined treatment for financial reasons and died 3 mo later. CONCLUSION Metastatic cutaneous lesions could indicate pancreatic cancer. Serum levels of tumor biomarkers may aid in diagnosing metastatic pancreatic adenocarcinoma.

Recent studies reported that serum anion gap could be regarded as a prognostic biomarker for patients admitted to intensive care units. However, the association between AG and mortality in cerebral infarction patients remained largely unknown.Relevant clinical data were collected from Medical Information Mart for Intensive Care III. Patients were divided into three groups according to tertiles of AG. Kaplan-Meier curve and Cox proportional hazards models were used to evaluate the association between AG levels and all-cause mortality. Subgroup analyses were performed to verify the predictive role of AG on mortality.Kaplan-Meier analysis showed that patients with higher AG had shorter survival time. Cox regression model indicated high AG as an independent risk factor of 30-day, 60-day and 180-day all-cause mortality (30-day: HR = 2.45, 95% CI = 1.21-4.97, 60-day: HR = 2.04, 95% CI = 1.07-3.89, and 180-day: HR = 1.85, 95% CI = 1.02-3.36). However, no significance was observed between AG and 365-day all-cause mortality (HR = 1.56, 95% CI = 0.87-2.78).High AG was associated with increased risk of all-cause mortality, and AG could be an independent short-term prognostic factor for cerebral infarction.

Background Interleukin-20 (IL-20) is closely related to cardiovascular diseases such as atherosclerosis. The relevance of IL-20 expression in human chronic heart failure (CHF) remains unknown. Thus, we investigated the level of circulating IL-20 in CHF patients and observed its correlation with CHF outcomes. Methods A cohort study was performed with CHF patients. Blood samples of 180 CHF patients and 167 control subjects were collected, and the plasma IL-20 level of each patient was determined. In addition, the endpoints of cardiovascular events among the CHF patients were evaluated prospectively. The maximum follow-up time of these CHF patients was 24 months, and the median follow-up time was 21 months. Results IL-20 levels were high in CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II, the NYHA III and the NYHA IV groups. According to the low, middle and high tertiles of IL-20 levels, the CHF patients were respectively divided into groups 1, groups 2, and groups 3. Multivariate Cox hazard analysis showed that the group 3 exhibited significantly higher cardiac event morbidity than the other two groups after adjustment for confounding factors. The CHF patients were also divided into two groups according to plasma IL-20 levels, and higher rates of cardiovascular events were observed in the group with higher IL-20 levels. Conclusions Circulating IL-20 levels are significantly elevated in CHF patients, and higher IL-20 levels suggest poorer outcomes in CHF patients.

Purpose GALAD is a statistical model for estimating the likelihood of having hepatocellular carcinoma (HCC) based on gender, age, AFP, AFP-L3, and PIVKA-II. We aimed to assess its performance and build new models in China, where hepatitis B virus (HBV) is the leading etiology of HCC. Patients and methods We built the GALAD-C model with the same five variables in GALAD, and the GAAP model with gender, age, AFP, and PIVKA-II, using logistic regression based on 242 patients with HCC and 283 patients with chronic liver disease (CLD). We also collected 50 patients with other malignant liver tumors (OMTs) and 50 healthy controls (HCs). A test dataset (169 patients with HCC and 139 with CLD) was used to test the performance of GAAP. Results The GALAD-C and GAAP models achieved comparable performance (area under the receiver operating characteristic curve [AUC], 0.922 vs 0.914), and both were superior to GALAD, PIVKA-II, AFP, and AFP-L3% (AUCs, 0.891, 0.869, 0.750, and 0.711) for discrimination of HCC from CLD for the entire dataset. The AUCs of the GALAD, GALAD-C and GAAP models were excellent for the hepatitis C virus (HCV) subgroup (0.939, 0.958 and 0.954), and for discrimination HCC from HCs (0.988, 0.982, and 0.979), but were relatively lower for the HBV subgroup (0.855, 0.904, and 0.894), and for HCC within Milan Criteria (0.810, 0.841, and 0.840). They were not superior to AFP (0.873) for discrimination of HCC from OMT (0.873, 0.809, and 0.823). GAAP achieved an AUC of 0.922 in the test dataset. Conclusion GALAD was excellent for discrimination of HCC from CLD in the HCV subgroup of a cohort of Chinese patients. The GAAP and GALAD-C models achieved better performance compared with GALAD. These three models exhibited better performance in patients with an HCV etiology than those with HBV.

Aim Some patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rapidly develop to critical condition. Here, we investigated the clinical features of critically ill SARS-CoV-2 patients with and without diabetes and identified risk factors for death of these patients. Methods The medical records including epidemiological, demographic, clinical, and laboratory data from 49 critically ill SARS-CoV-2 patients were collected and analyzed in Huanggang City and Xiaogan City, Hubei Province, outside Wuhan. Results Sixty-seven percent (33) of patients survived and 33% (16) of patients died in 49 critically ill patients (32 men, 17 women), with a median age of 63 years (IQR 53–73). Univariate analyses indicated that the deceased patients were more often associated with two or more comorbidities, one or more gastrointestinal symptoms, high neutrophil percentage, low lymphocytes and lymphocyte percentage, high C-reactive protein, high procalcitonin, high fasting blood glucose (FBG), and high lactate dehydrogenase (LDH) compared with the survivors; moreover, the patients with T2DM had the higher neutrophil percentage, the lower lymphocyte percentage, and the higher levels of FBG and LDH compared with the patients without T2DM. Multivariable logistic regression analyses indicated that gastrointestinal symptoms (≥ 1 symptoms), decreased lymphocytes (

Multidrug‐resistant tuberculosis (MDR‐TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR‐TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR‐TB, a mass spectrometry strategy of data‐independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR‐TB group and the drug‐sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR‐TB. Our study has paved the way for a novel method to diagnose MDR‐TB and may contribute to elucidate the mechanisms underlying MDR‐TB.

Background An alternative therapy for sporotrichosis is necessary to reduce the treatment time and raise clinical efficacy. The 5-Aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) is a promising platform with which to treat mycoses. However, despite the worldwide prevalence of Sporothrix globosa, a causative agent of sporotrichosis, the effect of ALA-PDT on this pathogen has not been validated. Objectives The aim of this study was to evaluate the effect of ALA-PDT on S globosa and the protection of melanin through an in vitro study. The mechanisms involved were also investigated. Methods To estimate the survival rate of S globosa treated with ALA-PDT and the protection offered by melanin, the conidia and yeast cells of wild-type S globosa (Mel+), other clinical strains, tricyclazole-treated Mel+ and an albino mutant strain (Mel-) were incubated with and without ALA or irradiation. Reactive oxygen species generation by Mel+ conidia induced by ALA-PDT was assayed. SEM and TEM were conducted to obverse ultrastructural changes in the conidia. A comet assay was performed to evaluate DNA damage. Results The survival rate of S globosa conidia and yeast cells significantly decreased following incubation with 1.19M ALA and 162 J/cm2 irradiation in vitro. Melanin was not only capable of protecting the conidia against ALA-PDT, but also against ALA or irradiation alone. After induction by ALA-PDT, alterations in reactive oxygen species generation, DNA damage and ultrastructural changes were observed. Conclusions ALA-PDT inhibits the survival of S globosa conidia in vitro and therefore has potential for the treatment of sporotrichosis.

Background Inflammatory pseudotumor of the liver (IPTL) is misdiagnosed usually as a malignant tumor based on the imaging findings. Differential diagnosis should be established to avoid hepatic resection. At imaging, IPTL has been misdiagnosed usually as hepatocellular carcinoma (HCC). It is usually found firstly using conventional ultrasonic examination, which cannot give a definitive diagnosis. Because of its atypical clinical presentation and radiological appearance, a presumptive diagnosis of malignancy is frequently made. With the development of ultrasound systems and ultrasound contrast agents (UCA), contrast-enhanced ultrasound is widely used in diagnosing focal lesions of the liver. Objectives To delineate the hemodynamic features of IPTL compared with hepatic VX2 tumor and normal liver using contrast-enhanced ultrasound. Material and methods Freund's complete adjuvant (FCA) was injected using a modified method into the desirable portion of the liver in rabbits. Two weeks after the injection, solitary IPTLs were formed (which was proved with pathological examination). Ten rabbits with IPTL, 10 rabbits with VX2 carcinoma and 10 healthy rabbits were studied using contrast-enhanced ultrasound with bolus injection of SonoVueTM through the peripheral vein. Corresponding parameters such as time to enhancement (ET), time to peak intensity (PIT), time to ascent (AT), and time to lighten (LT) were measured with wash-in/wash-out curve. Results Contrast-enhanced imaging clearly delineated the dynamic enhancement of the lesions and liver parenchyma during the whole phase. Inflammatory pseudotumor of the liver showed the same enhanced features as the liver parenchyma. In VX2 tumors, hyperechoic enhancement in arterial phase and hypoechoic enhancement was observed in the portal and delayed phase compared with the surrounding hepatic parenchyma. The normal liver showed whole of liver parenchyma enhanced in portal phase. Conclusions The study showed that contrast-enhanced ultrasound provided useful information about perfusion in IPTL and VX2 carcinoma. Contrast-enhanced ultrasound is a useful technique in the differential diagnosis of focal liver lesions if combined with time-intensity curve.

Objectives Understanding the nature of Mycobacterium leprae transmission is vital to implement better control strategies for leprosy elimination. The present study expands the knowledge of county-level strain diversity, distribution, and transmission patterns of leprosy in endemic provinces of China. Methods We genetically characterized 290 clinical isolates of M. leprae from four endemic provinces using variable number tandem repeats (VNTR) and single nucleotide polymorphisms (SNPs). Attained genetic profiles and cluster consequences were contrasted with geographical and migration features of leprosy at county levels. Results Considering the allelic variability of 17 VNTR loci by the discriminatory index, (GTA)9, (AT)17, (AT)15, (TA)18, (TTC)21, and (TA)10 are reported to be more highly polymorphic than other loci. The VNTR profile generated the low-density clustering pattern in the counties of Sichuan and Yunnan, whereas clusters have been observed from the isolates from Huayuan (N = 6), Yongding (N = 3), Zixing (N = 3), Chenxi (N = 2) and Zhongfang (N = 2) counties of Hunan, and Zhijin (N = 3), Anlong (N = 2), Zhenning (N = 2), and Xixiu (N = 2) counties of Guizhou. In some clusters, people’s social relations have been observed between villages. From the 290 clinical isolates, the most predominantly reported SNP was 3K (278, 95.8%), followed by SNP 1D (10, 3.4%), which are typically observed to be predominant in China. We also detected the novel SNP 3J (2, 0.8%), which has not yet been reported in China. Conclusion The clustering pattern of M. leprae indicates the transmission of leprosy still persists at county levels, suggesting that there is a need to implement better approaches for tracing the close contacts of leprosy patients.

Reasons behind the rapid increase of thyroid cancer (TC) in China are uncertain. We assessed the burden of TC and the role of access to screening and salt iodization. We analyzed two national databases in China: Hospital Quality Monitoring System (HQMS) and China Reinsurance Company (CRC) database. HQMS covered 1037 (44.3%) Class 3 hospitals and 76 263 617 Class 3 hospital inpatients in 2013 to 2017 and CRC covered 93 123 018 clients in 2000 to 2016. The proportion of TC inpatients among inpatients in HQMS and TC incidence in critical illness insurance buyers were used to evaluate the association with screening and iodine status. Between 2013 and 2017, the proportion of TC patients in HQMS with urban employee medical insurance and good access to screening increased sharply while there was little change among those with the other two forms of medical insurance. Across provinces, the proportion of TC inpatients in HQMS was positively correlated with per capita disposable income but not with median urinary iodine. Similar findings were observed in the CRC database. In 2017, approximately 1000 individuals were overdiagnosed with TC daily. We conservatively forecast that 5.1 million healthy individuals would become TC patients unnecessarily between 2019 and 2030. Our findings suggested the epidemic of TC in China was substantially underestimated. It was associated with screening but not with salt iodization., What's new? In recent decades, the incidence of thyroid cancer has increased rapidly worldwide. In China, the role of thyroid cancer screening as part of regular health checks and potential overdiagnosis remain unclear. Moreover, there are concerns among the general public that mandatory salt iodization may have contributed to the epidemic of thyroid cancer. Here, the authors found that the increase in thyroid cancer in China is associated with increased access to health care and screening, but not with salt iodization. Moreover, the results suggest that approximately 1000 individuals are overdiagnosed with thyroid cancer daily, calling for urgent measures to prevent overdiagnosis.

Many patients suffer from multiple organ dysfunction syndrome (MODS), which represents a dominant cause of death in the intensive care unit. Current theories about the mechanisms of MODS include inflammation, dysregulated immune response, reduced cellular oxygen utilization, cytopathic hypoxia, and apoptosis. Moreover, an increasing number of studies have shown that endoplasmic reticulum stress (ERS) is related to organ dysfunction. The endoplasmic reticulum is an organelle that is responsible for secretion and membrane protein synthesis and assembly as well as some other physiological activities. Under certain conditions, the homeostasis of ER can be lost, causing the accumulation of unfolded or misfolded protein, which is termed as ERS. During ERS, unfolded protein response (UPR) is activated. Once UPR fails to rebuilt cellular homeostasis, cell function will be impaired and apoptosis will be induced. To better understand the relationship between ERS and severe diseases, we summarize the current research in the context of ERS and UPR signaling associated with various organ dysfunction and severe diseases, including acute lung injury, hepatic injury, heart failure, hemorrhagic shock with multiple organ dysfunction, sepsis, and some other diseases. We also discuss ERS or UPR as a novel therapeutic target and their future directions.

China faces the greatest challenge from stroke in the world. The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018. It ranked third among the leading causes of death behind malignant tumours and heart disease. The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively. According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017. The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017. The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)). The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%). The least prevalent was AF (2.7%-7.4%). The prevalences for major risk factors for stroke are high and most have increased over time. Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products. For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%. For those aged ≥40 years, the standardised prevalence of AF was 2.31%. Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018. Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs). The average age of patients admitted was 66 years old, and nearly 60% were male. A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age

Recent, research has displayed that the disorders of miR-18b are related to ischemic stroke. Here, we aimed to investigate the underlying neuroprotective mechanism of miR-18b in cerebral ischemia/reperfusion (I/R) injury. Oxygen-glucose deprivation/reperfusion (OGDR) model in vitro and middle cerebral artery occlusion (MCAO) model in vivo were established to simulate cerebral I/R injury. RT-PCR, western blotting, CCK-8, TUNEL, and TTC staining assays were applied in this study to explore the effect of miR-18b on cerebral I/R injury. Results displayed that miR-18b expression was reduced after cerebral I/R injury. Besides, miR-18b showed neuroprotective effects on cerebral I/R injury both in vitro and in vivo, These neuroprotective effects included promoting cell viability, decreasing cell apoptosis, reducing the production of inflammatory cytokines in SH-SY 5Y cells after OGDR and depressing MCAO-induced infarct size, neurological deficits and apoptotic cells in mice. Moreover, miR-18b negatively regulated ANXA3 expression, and its neuroprotection on cerebral I/R injury was overturned by ANXA3. Additionally, increasing miR-18b or decreasing ANXA3 promoted the activation of the PI3K/Akt signaling pathway in SH-SY 5Y cells after cerebral I/R injury. In conclusion, these data indicate that miR-18b protects against cerebral I/R injury by inhibiting ANXA3 and activating PI3K/Akt pathway, which provides a promising therapeutic target for ischemic stroke therapy.

Background: This study proposed to quantitatively assess the value of spectral CT imaging parameters in differentiating different pathological types of lung cancer. Methods: Eighty five patients with lung cancer (66 non-mucinous adenocarcinomas, 7 Squamous cell carcinomas, 8 small cell carcinomas, 1 mucinous adenocarcinoma, 1 sarcomatoid carcinoma, 1 carcinoid, 1 large cell carcinoma) underwent CT plain scan, contrast enhanced CT scans in arterial phase (a) and venous phase (v) with spectral imaging mode on a GE Revolution Xtream CT scanner. The Spectral CT Imaging parameters: Iodine concentrations (IC) of lesion in arterial phase (ICLa) and venous phase (ICLv), Normalized IC (NICa/NICv)-normalized to the IC in the aorta, slope of the spectral HU curve (λHUa/λHUv) and monochromatic CT number (CT40keVa/CT40keVv, CT70keVa/CT70keVv) enhancement on 40 keV and 70 keV images were calculated. The One-way ANOVA or Kruskal-Wallis test was used to compare quantitative parameters among lung squamous carcinoma, small cell carcinoma and lung adenocarcinoma groups, Bonferroni method was used to correct P value for multiple comparisons. Results: Among the different pathological types of lung cancers, these quantitative parameters of spectral CT imaging CT70keVa has significant difference. The CT70keVa of lung adenocarcinoma was lower than small cell carcinoma (P = 0.048) and squamous cell carcinoma (P = 0.039), respectively. And these CT40keVa, CT70keVa/CT70keVv parameters of lung adenocarcinoma was lower than non-adenocarcinomas (P < 0.05). However, there was no significant difference in spectral CT parameters between small cell lung cancer and squamous cell lung cancer, small cell lung cancer and non-small cell carcinoma (P > 0.05). Conclusion: Spectral CT parameters may be of value in distinguishing different pathological types of lung cancer.

Background The aim of this work is to combine radiological and pathological information of tumor to develop a signature for pretreatment prediction of discrepancies of pathological response at several centers and restage patients with locally advanced rectal cancer (LARC) for individualized treatment planning. Patients and Methods A total of 981 consecutive patients with evaluation of response according to tumor regression grade (TRG) who received nCRT were retrospectively recruited from four hospitals (primary cohort and external validation cohort 1–3); both pretreatment multiparametric MRI (mp-MRI) and whole slide image (WSI) of biopsy specimens were available for each patient. Quantitative image features were extracted from mp-MRI and WSI and used to construct a radiopathomics signature (RPS) powered by an artificial-intelligence model. Models based on mp-MRI or WSI alone were also constructed for comparison. Results The RPS showed overall accuracy of 79.66–87.66% in validation cohorts. The areas under the curve of RPS at specific response grades were 0.98 (TRG0), 0.93 (≤ TRG1), and 0.84 (≤ TRG2). RPS at each grade of pathological response revealed significant improvement compared with both signatures constructed without combining multiscale tumor information (P P Conclusions The results of this study suggest that radiopathomics, combining both radiological information of the whole tumor and pathological information of local lesions from biopsy, could potentially predict discrepancies of pathological response prior to nCRT for better treatment planning.

Breast cancer (BC) is the most common cancer and the leading cause of death in women. Advances in early diagnosis and therapeutic strategies have decreased the mortality of BC and improved the prognosis of patients to some extent. However, the development of drug resistance has limited the success rate of systemic therapies. Long non-coding RNAs (lncRNAs) are involved in drug resistance in BC via various mechanisms, which contribute to a complex regulatory network. In this review, we summarize the latest findings on the mechanisms underlying drug resistance modulated by lncRNAs in BC. In addition, we discuss the potential clinical applications of lncRNAs as targeted molecular therapy against drug resistance in BC.

Colorectal cancer (CRC) is one of the most common cancers worldwide, with high mortality. Abnormally expressed microRNAs (miRNAs) are considered novel biomarkers in cancer diagnosis. The aim of this study was to investigate the diagnostic value of miR‐92a‐1 in patients with CRC. Serum samples were collected from 148 patients pathologically diagnosed with CRC and 68 gender‐ and age‐matched healthy volunteers. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to measure serum miR‐92a‐1 level. Relationship between miR‐92a‐1 and clinicopathological features of CRC cases was analysed via chi‐square test. Receiver operating characteristic (ROC) curve was plotted to estimate the diagnostic value of miR‐92a‐1 in CRC. Serum miR‐92a‐1 was significantly up‐regulated in CRC patients compared with healthy individuals (P

As a critical factor involved in the maintenance of physiological homeostasis, the gut microbiota (GM) reportedly plays a key role in bone development. To date, the association between the GM and steroid deficiency-induced osteoporosis remains poorly understood. Forty female Sprague Dawley rats were divided into an ovariectomy (OVX) or control group. We performed 16S rRNA and metagenome sequencing, to compare diversity, taxonomic differences, and functional genes. The GM composition did not change in the control group and the number of operational taxonomic units increased significantly following ovariectomy. Alpha diversity, determined by ACE estimator, CHAO estimator, the Shannon index, and the Simpson index showed an increasing trend after ovariectomy. Samples in the OVX group were well clustered both pre- and post-ovariectomy, as demonstrated by principal coordinate 1 (PC1) and PC2. Functional genes of GM, including those involved in synthesis and metabolism of carbohydrates and nucleotides, microbial structure, and heme, as well as hemin uptake and utilization, increased at the early stage of osteoporosis. We observed that Ruminococcus flavefaciens exhibited the greatest variation in abundance among the GM and this was also associated with osteoclastic indicators and the estrobolome. Specific changes in fecal microbiota are associated with the pathogenesis of steroid deficiency-induced osteoporosis.

Background Epidemiological data on Treponema pallidum infection are scarce from the southwestern region of China. The purpose of this study was to determine the distribution and determinants of T. pallidum infection in the region. Methods A community-based cross-sectional study of 2608 participants aged ≥14 years was conducted in a rural area of southwestern China in 2014–15. A pretested questionnaire was used to collect sociodemographic characteristics and other factors associated with T. pallidum infection. The diagnoses of T. pallidum, human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV) infections were determined by commercial test kits. Logistic regression analysis was used to determine the correlates for T. pallidum infection, and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Results The prevalence of T. pallidum infection was 1.2% (95% CI 0.8 to 1.7%). Risk factors varied by gender. In the male group, T. pallidum infection was significantly associated with ever injection drug use (aOR = 9.42, 95% CI 2.47 to 35.87) and HCV infection (aOR = 13.28, 95% CI 3.20 to 51.70). In the female group, correlates for T. pallidum infection included spouse having syphilis (aOR = 126.66, 95% CI 7.58 to 2122.94), ever having blood transfusion (aOR = 10.51, 95% CI 1.58 to 41.21) and HBV infection (aOR = 4.19, 95% CI 1.35 to 10.93). Conclusions The prevalence of T. pallidum infection was high in the rural area of southwestern China. Correlates for T. pallidum infection varied with sex specific. Intervention should be developed for the prevention and control of T. pallidum infection.

Background Multiple acyl-CoA dehydrogenase deficiency (MADD) is an uncommon autosomal recessive disorder of mitochondrial fatty acid beta-oxidation. Syncope is a transient loss of consciousness due to acute global cerebral hypoperfusion. Late-onset MADD with syncope has not been reported previously. Case summary We report a 17-year-old girl with exercise intolerance and muscle weakness. She felt palpitation and shortness of breath after short bouts of exercise. She also suffered from a transient loss of consciousness many times. Muscle biopsy showed lipid storage. Genetic mutation analysis indicated a compound heterozygous mutation c.250G > A (p.A84T) and c.872T > G (p.V291G) in the ETFDH gene. The results of Holter electrocardiogram monitoring showed supraventricular tachycardia when the patient experienced a loss of consciousness. After treatment with riboflavin and carnitine, muscle weakness and palpitation symptoms improved rapidly. No loss of consciousness occurred, and the Holter electrocardiogram monitoring was normal. Conclusion Late-onset MADD with supraventricular tachycardia can cause cardiac syncope. Carnitine and riboflavin supplement were beneficial for treating the late-onset MADD with cardiac syncope. Attention should be paid to the prevention of cardiac syncope when diagnosing late-onset MADD.

Background The aim of the study was to develop a deep learning (DL) algorithm to evaluate the pathological complete response (pCR) to neoadjuvant chemotherapy in breast cancer. Methods A total of 302 breast cancer patients in this retrospective study were randomly divided into a training set (n = 244) and a validation set (n = 58). Tumor regions were manually delineated on each slice by two expert radiologists on enhanced T1‐weighted images. Pathological results were used as ground truth. Deep learning network contained five repetitions of convolution and max‐pooling layers and ended with three dense layers. The pre‐NAC model and post‐NAC model inputted six phases of pre‐NAC and post‐NAC images, respectively. The combined model used 12 channels from six phases of pre‐NAC and six phases of post‐NAC images. All models above included three indexes of molecular type as one additional input channel. Results The training set contained 137 non‐pCR and 107 pCR participants. The validation set contained 33 non‐pCR and 25 pCR participants. The area under the receiver operating characteristic (ROC) curve (AUC) of three models was 0.553 for pre‐NAC, 0.968 for post‐NAC and 0.970 for the combined data, respectively. A significant difference was found in AUC between using pre‐NAC data alone and combined data (P

The lack of rapid and efficient diagnostics impedes largely the epidemic control of multidrug-resistant tuberculosis, and might misguide the therapeutic strategies as well. This study aimed to identify novel multidrug-resistant tuberculosis biomarkers to improve the early intervention, symptomatic treatment and control of the prevalence of multidrug-resistant tuberculosis. The serum small molecule metabolites in healthy controls, patients with drug-susceptible tuberculosis, and patients with multidrug-resistant tuberculosis were screened using ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The differentially abundant metabolites were filtered out through multidimensional statistical analysis and bioinformatics analysis. Compared with drug-susceptible tuberculosis patients and healthy controls, the levels of 13 metabolites in multidrug-resistant tuberculosis patients altered. Among them, the most significant changes were found in N1-Methyl-2-pyridone-5-carboxamide (N1M2P5C), 1-Myristoyl-sn-glycerol-3-phosphocholine (MG3P), Caprylic acid (CA), and D-Xylulose (DX). And a multidrug-resistant tuberculosis/drug-susceptible tuberculosis differential diagnostic model was built based on these four metabolites, achieved the accuracy, sensitivity, and specificity of 0.928, 86.7%, and 86.7%, respectively. The enrichment analysis of metabolic pathways showed that the phospholipid remodeling of cell membranes was active in multidrug-resistant tuberculosis patients. In addition, in patients with tuberculosis, the metabolites of dipalmitoyl phosphatidylcholine (DPPC), a major component of pulmonary surfactant, were down-regulated. N1M2P5C, MG3P, CA, and DX may have the potential to serve as novel multidrug-resistant tuberculosis biomarkers. This research provides a preliminary experimental basis to further investigate potential multidrug-resistant tuberculosis biomarkers. Impact statement The MDR-TB incidence remains high, making the effective control of TB epidemic yet challenging. Rapid and accurate diagnosis is vitally important for improving the therapeutic efficacy and controlling the prevalence of drug resistance TB. Metabolomics has dramatic potential to distinguish MDR-TB and DS-TB. N1M2P5C, MG3P, CA, and DX that we identified in this study might have potential as novel MDR-TB biomarkers. The phospholipid remodeling of cell membranes was highly active in MDR-TB. The DPPC metabolites in TB were significantly down-regulated. This work aimed to investigate potential MDR-TB biomarkers to enhance the clinical diagnostic efficacy. The metabolic pathway distinctly altered in MDR-TB might provide novel targets to develop new anti-TB drugs.

ObjectivesOur objective was to determine the impact of maternal HIV–hepatitis B virus (HBV) coinfection on pregnancy outcomes.MethodsThe current study was conducted in a county of Yi Autonomous Prefecture in southwest China. Data were abstracted from hospitalisation records, including maternal and infant information. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were determined and the impact of maternal HIV–HBV coinfection on adverse pregnancy outcomes was assessed using logistic regression analysis. A treatment effects linear regression model was also applied to examine the effect of HBV, HIV or coinfection to quantify the absolute difference in birth weight from a reference of HBV–HIV negative participants.ResultsA total of 13 198 pregnant women were included in our study, and among them, 99.1% were Yi people and 90.8% lived in rural area. The seroprevalences of HIV and HBV infections and HIV–HBV coinfection were 3.6% (95% CI: 3.2% to 3.9%), 3.2% (95% CI: 2.9% to 3.5%) and 0.2% (95% CI: 0.1% to 0.2%) among the pregnant women, respectively. Maternal HIV–HBV coinfection was a risk factor for low birth weight (adjusted OR (aOR)=5.52, 95% CI: 1.97 to 15.40). Compared with the HIV mono-infection group, the risk of low birth weight was significantly higher in the HIV–HBV coinfection group (aOR=3.62, 95% CI: 1.24 to 10.56). Maternal HIV infection was associated with an increased risk of low birth weight (aOR=1.90, 95% CI: 1.38 to 2.60) and preterm delivery (aOR=2.84, 95% CI: 1.81 to 4.47). Perinatal death was more common when mothers were infected with HBV (aOR=2.85, 95% CI: 1.54 to 5.26).ConclusionsThe prevalence of HIV infection was high among pregnant women of the Yi region. Both HIV and HBV infections might have adverse effects on pregnancy outcomes. Maternal HIV–HBV coinfection might be a risk factor for low birth weight in the Yi region, which needs to be confirmed.

Introduction To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. Methods A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. Results There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P P P P > 0.05). Conclusions The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.