Cover illustration
Bone marrow aspirate smear demonstrating blasts cells (High power) stained with Wrigh-Giemsa from a patient with Philadelphia chromosome-positive acute lymphoblastic leukemia. The patient achieved molecular complete remission after received imatinib plus CALLG2008 protocol.
The antibiotic resistance is natural in bacteria and predates the human use of antibiotics. Numerous antibiotic resistance genes (ARGs) have been discovered to confer resistance to a wide range of antibiotics. The ARGs in natural environments are highly integrated and tightly regulated in specific bacterial metabolic networks. However, the antibiotic selection pressure conferred by the use of antibiotics in both human medicine and agriculture practice leads to a significant increase of antibiotic resistance and a steady accumulation of ARGs in bacteria. In this review, we summarized, with an emphasis on an ecological point of view, the important research progress regarding the collective ARGs (antibiotic resistome) in bacterial communities of natural environments, human and animals, i.e., in the one health settings. We propose that the resistance gene flow in nature is “from the natural environments” and “to the natural environments”; human and animals, as intermediate recipients and disseminators, contribute greatly to such a resistance gene “circulation.”
Sensitive and useful biomarkers for the diagnosis and prognosis of infectious diseases have been widely developed. An example of these biomarkers is triggering receptor expressed on myeloid cell-1 (TREM-1), which is a cell surface receptor expressed on monocytes/macrophages and neutrophils. TREM-1 amplifies inflammation by activating the TREM-1/DAP12 pathway. This pathway is triggered by the interaction of TREM-1 with ligands or stimulation by bacterial lipopolysaccharide. Consequently, pro-inflammatory cytokines and chemokines are secreted. Soluble TREM-1 (sTREM-1) is a special form of TREM-1 that can be directly tested in human body fluids and well-known biomarker for infectious diseases. sTREM-1 level can be potentially used for the early diagnosis and prognosis prediction of some infectious diseases, including infectious pleural effusion, lung infections, sepsis, bacterial meningitis, viral infections (e.g., Crimean Congo hemorrhagic fever and dengue fever), fungal infections (e.g., Aspergillus infection), and burn-related infections. sTREM-1 is a more sensitive and specific biomarker than traditional indices, such as C-reactive protein and procalcitonin levels, for these infectious diseases. Therefore, sTREM-1 is a feasible biomarker for the targeted therapy and rapid and early diagnosis of infectious diseases.
Zebrafish is an emerging animal model for studies on auditory system. This model presents high comparability with humans, good accessibility to the hearing organ, and high throughput capacity. To better utilize this animal model, methodologies need to be used to quantify the hearing function of the zebrafish. Zebrafish displays a series of innate and robust behavior related to its auditory function. Here, we reviewed the advantage of using zebrafish in auditory research and then introduced three behavioral tests, as follows: the startle response, the vestibular-ocular reflex, and rheotaxis. These tests are discussed in terms of their physiological characteristics, up-to-date technical development, and apparatus description. Test limitation and areas to improve are also introduced. Finally, we revealed the feasibility of these applications in zebrafish behavioral assessment and their potential in the high-throughput screening on hearing-related genes and drugs.
Primary hepatic carcinoma (PHC) is a common malignant tumor in China. Cancer is comprehensively treated with various therapeutic regimes, including traditional Chinese medicine (TCM). TCM has been widely used to improve the quality of life, delay the time of cancer progression, and prolong the median survival time. This systematic review with meta-analysis aimed to assess the effect of TCM combined with Western therapy on primary hepatic carcinoma. A comprehensive literature search was conducted in six databases, including CNKI, VIP, Wan-Fang Database, CBM, PubMed, and Cochrane library. A total of 44 randomized controlled trials (RCTs) involving 3429 participants suffering from PHC were selected. Meta-analysis results indicated that the overall effect of TCM and Western integrative treatment on PHC was higher than that of Western intervention alone, which can postpone tumor recurrence and metastasis and prolong the overall survival time of patients with PHC. Although the obtained evidence remained weak because of the poor methodological quality of the included studies, this review provided relevant data supporting the efficacy and safety of TCM combined with Western therapies. In future research, individual RCT studies should incorporate accepted standards for trial design and reporting, proper outcome indicators according to international standards, blinding in allocation concealment, and valid follow-up periods.
In traditional Chinese medicine, Lonicerae Japonicae Flos is commonly used as anti-inflammatory, antiviral, and antipyretic herbal medicine, and geo-authentic herbs are believed to present the highest quality among all samples from different regions. To discuss the current situation and trend of geo-authentic Lonicerae Japonicae Flos, we searched Chinese Biomedicine Literature Database, Chinese Journal Full-text Database, Chinese Scientific Journal Full-text Database, Cochrane Central Register of Controlled Trials, Wanfang, and PubMed. We investigated all studies up to November 2015 pertaining to quality assessment, discrimination, pharmacological effects, planting or processing, or ecological system of geo-authentic Lonicerae Japonicae Flos. Sixty-five studies mainly discussing about chemical fingerprint, component analysis, planting and processing, discrimination between varieties, ecological system, pharmacological effects, and safety were systematically reviewed. By analyzing these studies, we found that the key points of geo-authentic Lonicerae Japonicae Flos research were quality and application. Further studies should focus on improving the quality by selecting the more superior of all varieties and evaluating clinical effectiveness.
MicroRNAs (miRNAs) play critical roles in the development and progression in various cancers. Dysfunctional miR-9 expression remains ambiguous, and no consensus on the metastatic progression of ovarian cancer has been reached. In this study, results from the bioinformatics analysis show that the 3′-UTR of the E-cadherin mRNA was directly regulated by miR-9. Luciferase reporter assay results confirmed that miR-9 could directly target this 3′-UTR. miR-9 and E-cadherin expression in ovarian cancer tissue was quantified by qRT-PCR. Migration and invasion were detected by wound healing and Transwell system assay in SKOV3 and A2780. qRT-PCR and Western blot were performed to detect the epithelial?mesenchymal transition-associated mRNA and proteins. Immunofluorescence technique was used to analyze the expression and subcellular localization of E-cadherin, N-cadherin, and vimentin. The results showed that miR-9 was frequently upregulated in metastatic serous ovarian cancer tissue compared with paired primary ones. Upregulation of miR-9 could downregulate the expression of E-cadherin but upregulate the expression of mesenchymal markers (N-cadherin and vimentin). Overexpression of miR-9 could promote the cell migration and invasion in ovarian cancer, and these processes could be effectively inhibited via miR-9 inhibitor. Thus, our study demonstrates that miR-9 may promote ovarian cancer metastasis via targeting E-cadherin and a novel potential therapeutic approach to control metastasis of ovarian cancer.
The objective of this study is to guide a triage for the management of cervical high-grade squamous intraepithelial lesion (HSIL) patients with positive margin by conization. Clinico-pathological data of HSIL patients with positive margin by conization were retrospectively collected from January 2009 to December 2014. All patients underwent secondary conization or hysterectomy within 6 months. The rate of residual lesion was calculated, and the factors associated with residual lesion were analyzed by univariate and multivariate analyses. Among a total of 119 patients, 56 (47.06%) patients presented residual HSIL in their subsequent surgical specimens, including 4 cases of invasive cervical carcinoma (3 stage IA1 and 1 stage IA2 patients). Univariate analysis showed that patient age>35 years (P=0.005), menopausal period>5 years (P=0.0035), and multiple-quadrant involvement (P=0.001) were significantly correlated with residual disease; however, multivariate analysis revealed that multiple-quadrant involvement (P=0.001; OR, 3.701; 95%CI, 1.496–9.154) was an independent risk factor for residual disease. Nearly half of HSIL patients with positive margin by conization were disease-free in subsequent surgical specimens, and those with multiple positive margins may consider re-conization or re-assessment.
A CALLG2008 protocol was developed by the Chinese Acute Lymphoblastic Leukemia Cooperative Group for adult acute lymphoblastic leukemia (ALL). We retrospectively analyzed 153 newly diagnosed adult patients with Philadelphia chromosome (Ph)-positive ALL enrolled into imatinib (400 mg/d) plus CALLG2008 regimen between 2009 and 2015. The median age was 40 years (range, 18–68 years), with 81 (52.3%) males. The overall hematologic complete remission (CR) rate was 96.7% after induction. With a median follow-up of 24.2 months, the estimated 3-year overall survival (OS) and event-free survival (EFS) rates were 49.5% (95% confidence interval (CI): 38.5%–59.5%) and 49.2% (95% CI: 38.3%–59.2%), respectively. Fifty-eight (36 with haploidentical donor) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first CR. Among the patients in CR1 after induction, both the 3-year OS and EFS were significantly better in the allo-HSCT group than in the without allo-HSCT group (73.2%, 95% CI: 58.3%–83.5% vs. 22.2%, 95% CI: 8.7%–39.6% and 66.5%, 95% CI: 50.7%–78.2% vs. 16.1%, 95% CI: 5.1%–32.7%, respectively). Multivariate analysis showed that allo-HSCT and achievement of major molecular response were associated with favorable OS or EFS independently. Interestingly, in the allo-HSCT cohort, the donor type (haploidentical versus matched donors) had no significant impact on EFS or OS. All these results suggested that imatinib plus CALLG2008 was an effective protocol for Ph-positive ALL. Haploidentical donors can also be a reasonable alternative expedient donor pool.
Patients undergoing major oncological surgery for head and neck cancer (SHNC) have a particularly high risk of nosocomial infections. We aimed to identify risk factors for ventilator-associated pneumonia (VAP) in patients undergoing SHNC. The study included 465 patients who underwent SHNC between June 2011 and June 2014. The rate of VAP, risk factors for VAP, and biological aspects of VAP were retrospectively evaluated. The incidence of VAP was 19.6% (n=95) in patients who required more than 48 h of mechanical ventilation. Staphylococcus (37.7%), Enterobacteriaceae (32.1%), Pseudomonas (20.8%), and Haemophilus (16.9%) were the major bacterial species that caused VAP. The independent risk factors for VAP were advanced age, current smoking status, chronic obstructive pulmonary disease, and a higher simplified acute physiology score system II upon admission. Tracheostomy was an independent protective factor for VAP. The median length of stay in the ICU for patients who did or did not develop VAP was 8.0 and 6.5 days, respectively (P=0.006). Mortality among patients who did or did not develop VAP was 16.8% and 8.4%, respectively (P<0.001). The potential economic impact of VAP was high because of the significantly extended duration of ventilation. A predictive regression model was developed with a sensitivity of 95.3% and a specificity of 69.4%. VAP is common in patients who are undergoing SHNC and who require more than 48 h of mechanical ventilation. Therefore, innovative preventive measures should be developed and applied in this high-risk population.
The activity of free radicals in follicular fluid was related to ovarian responsiveness, in vitro fertilization (IVF), and embryo transfer success rate. However, studies analyzing the relationship between the free radical scavenging capacity and embryo quality of infertile women with polycystic ovarian syndrome (PCOS) were lacking. The aim of this study was to evaluate the relationship between the free radical scavenging window of women with PCOS and their embryo quality. The free radical scavenging capacity of follicular fluid from women with PCOS was determined by a,a-diphenyl-b-picrylhydrazyl (DPPH), 2,2-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) assay, superoxide radical, and reactive oxygen species (ROS) assay. In the DPPH and ROS assays, the follicular fluid from grades I and II embryos was significantly higher than the follicular fluid from grades III and IV embryos. The lower control limit of DPPH radical scavenging capacity and upper control limit of ROS level were 13.2% and 109.0 cps, respectively. The calculated lower control limit and upper control limit were further confirmed in the follicular fluid of embryos of all grades. These cut-off values of free radical scavenging activity of follicular fluid could assist embryologists in choosing the development of embryos in PCOS patients undergoing IVF.
The main constituents of a typical medicinal herb, Polygonum multiflorum (Heshouwu in Chinese), that induces idiosyncratic liver injury remain unclear. Our previous work has shown that cotreatment with a nontoxic dose of lipopolysaccharide (LPS) and therapeutic dose of Heshouwu can induce liver injury in rats, whereas the solo treatment cannot induce observable injury. In the present work, using the constituent “knock-out” and “knock-in” strategy, we found that the ethyl acetate (EA) extract of Heshouwu displayed comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Results indicated a significant elevation of plasma alanine aminotransferase, aspartate aminotransferase, and liver histologic changes, whereas other separated fractions failed to induce liver injury. The mixture of EA extract with other separated fractions induced comparable idiosyncratic hepatotoxicity to the whole extract in LPS-treated rats. Chemical analysis further revealed that 2,3,5,4'-tetrahydroxy trans-stilbene-2-O-β-glucoside (trans-SG) and its cis-isomer were the two major compounds in EA extract. Furthermore, the isolated cis-, and not its trans-isomer, displayed comparable idiosyncratic hepatotoxicity to EA extract in LPS-treated rats. Higher contents of cis-SG were detected in Heshouwu liquor or preparations from actual liver intoxication patients associated with Heshouwu compared with general collected samples. In addition, plasma metabolomics analysis showed that cis-SG-disturbing enriched pathways remarkably differed from trans-SG ones in LPS-treated rats. All these results suggested that cis-SG was closely associated with the idiosyncratic hepatotoxicity of Heshouwu. Considering that the cis-trans isomerization of trans-SG was mediated by ultraviolet light or sunlight, our findings serve as reference for controlling photoisomerization in drug discovery and for the clinical use of Heshouwu and stilbene-related medications.
Childhood obesity and obesity-related metabolic complications are induced by a high-fat postnatal diet. The lack of a suitable animal model, however, remains a considerable challenge in obesity studies. In the current study, we provided high-fat diet (HFD) to dams during lactation and to pups after weaning. We also developed a novel model of C57BL/6J mouse pups with HFD-induced postnatal obesity. Results showed that feeding with HFD induces fat deposition and obesity in pups. Furthermore, HFD more potently increased the body weight (BW) of male than female pups. HFD-fed female pups were obese, underwent precocious puberty, and showed increased kisspeptin expression in the hypothalamus. However, parental obesity and precocious puberty exerted no synergistic effects on the HFD-induced postnatal weight gain and puberty onset of the pups. Interestingly, some HFD-fed litters with normal BW also exhibited precocious puberty. This finding suggested that diet composition but not BW triggers puberty onset. Our model suggests good construction validity of obesity and precocious puberty. Furthermore, our model can also be used to explore the mutual interactions between diet–induced postnatal childhood obesity and puberty.
This study aims to investigate the effect of non-transecting anastomotic urethroplasty for treatment of posterior urethral stricture. A total of 23 patients with traumatic posterior urethral stricture were enrolled and then divided into two groups. In one group, 12 patients underwent non-transecting anastomotic urethroplasty. In the other group, 11 patients underwent conventional posterior urethra end-to-end anastomosis. The effect of operation was evaluated using the following parameters: the bleeding amount during operation, operation time, IIEF-5 scores after operation, maximum flow rate (Qmax), and rating scale of quality of life (QoL). The comparison between the conventional posterior urethra end-to-end anastomosis group and the non-transecting anastomotic urethroplasty group showed no significant difference with regard to average operation time. However, a significant difference was observed between the groups with regard to the bleeding amount during operation. The patients in the group of non-transecting anastomotic urethroplasty urinated smoothly after the removal of catheter. Meanwhile, one patient from the group of conventional posterior urethra end-to-end anastomosis had difficulty urinating after the removal of catheter. Furthermore, significant differences in the operation time, bleeding amount during operation, IIEF-5 scores after operation, and rating scale of QoL were observed, whereas no significant difference was observed between urine flow rates of the two groups after operation. Overall, non-transecting anastomotic urethroplasty is effective for posterior urethra reconstruction, and it can reduce the occurrence rate of erectile dysfunction after operation.
Arsenic trioxide (ATO), a component of the traditional Chinese medicine arsenic sublimate, promotes apoptosis and induces leukemic cell differentiation. Combined with all-trans-retinotic acid (ATRA), ATO has become the first-line induction therapy in treating acute promyelocytic leukemia (APL). The most common side effects of ATO include hepatotoxicity, gastrointestinal symptoms, water-sodium retention, and nervous system damage. In this report, we present a rare side effect, rhabdomyolysis, in a 68-year-old female APL patient who was treated with ATO. After taking 10 mg ATO daily for 6 days, she presented shortness of breath, myodynia, elevated creatine kinase, and acute renal insufficiency. This report describes the first case of ATO-induced rhabdomyolysis.
Castleman disease (CD) is an uncommon non-clonal lymphoproliferative disorder with unknown etiology. No standard therapy is recommended for relapsed/refractory CD patients, thus requiring development of novel experimental approaches. Our cohort of three adult patients with multicentric CD (MCD) were treated with refractory to traditional chemotherapy lenalidomide-containing regimens (10–25 mg lenalidomide perorally administered on days 1–21 in 28-day cycle) as second- to fourth-line treatment. Partial remission was achieved in first plasma-cell CD patient, who relapsed seven months after autologous hematopoietic stem cell transplantation and then failed to respond to four cycles of chemotherapy. Partial remission was obtained in second patient with CD and polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes syndrome. Third case showed complete remission with complete disappearance of pleural effusion and ascites and normalization of platelet count. To conclude, encouraging clinical responses were achieved in cohort of three patients with lenalidomide-based regimen, though long-term efficacy remains to be observed. We propose further investigation of therapeutic potential of this drug in treating MCD.
Familial amyloid cardiomyopathy is a challenging condition that mimics many other diseases, particularly in patients with pronounced neurological presentations and unexplained or equivocal cardiac abnormalities. In this case, a 57-year-old man was admitted for outpatient cardiological evaluation of progressive right heart failure and limb paraesthesias. The patient presented with hypertension, chronic Guillain-Barre syndrome, and sick sinus syndrome. Transthoracic echocardiograms showed a thickened ventricular wall and enlarged atrium. Tissue Doppler showed a restrictive filling pattern. Transthyretin (TTR)-associated amyloidosis, which was revealed by abdominal fat-pad biopsy and DNA analysis, explained the concurrence of independent pathological features, including neuropathy and cardiac involvement. Genetic testing identified a G>T mutation in exon 4 of the transthyretin (TTR) gene. This mutation resulted in the alanine-to-serine substitution at amino acid position 117. Moreover, genetic testing confirmed that the patient’s asymptomatic son carried the same amyloidogenic TTR mutation. Given these findings, the diagnosis of familial amyloid cardiomyopathy, which was misdiagnosed as chronic Guillain-Barre syndrome, was proposed.
Innovative development extends the vitality of ethnomedicines. Developing ethnomedicines is not only beneficial to the public but also to the related industry and transforms economic growth, driving local social and economic development further. Its economic benefit can be used to optimize and promote the hardware and software of the platform, as well as support the sustainable development of ethnomedicines. Apart from research and discussion on the innovative development of ethnomedicines on the basis of theory and regulations, this series of articles also summarizes cases that are conducive to the overall understanding of the necessity and feasibility of the innovative development. In terms of industrial development, large enterprises and products, such as Yunnan Baiyao, Guizhou Miao ethnomedicines, Cheezheng Tibetan Medicine, products developed from Dengzhanhua (Erigeron breviscapus), the Gold series of Yi ethnomedicines, and products developed from Sanqi (Panax notoginseng), in China are introduced and summarized, focusing on resource superiority, sustainable innovation, standard research and development, and production, as well as intellectual property protection.