[Pathogenesis and Therapeutic Prospects of Chronic Graft-Versus-Host Disease --Review].

Chronic graft-versus-host disease (cGVHD) is one of a major complication that affecting the long-term survival and living quality of patients after allogeneic hematopoietic stem cell transplantation, with the incidence of 30%-70%. Unlike acute GVHD, cGVHD involves a large number of immune cells and cytokines in addition to T cell, which is activated abnormally by the donor, and cytokine storms, which characterized by infiltration of donor lymphocytes and damage to host target organ. Recent studies have further made progress in targeting related immune cells and cytokines. In this review, the pathogenesis and therapeutic prospects of cGVHD were summarized from the perspectives of classical innate and adaptive immunity.

Clinical Evaluation of the BIOFIRE SPOTFIRE Respiratory Panel.

The BIOFIRE SPOTFIRE Respiratory (R) Panel is a novel, in vitro diagnostic PCR assay with 15 pathogen targets. The runtime is about 15 min which is the shortest among similar panels in the market. We evaluated the performance of the SPOTFIRE R Panel with 151 specimens, including 133 collected from the upper respiratory tract (URT), 13 from the lower respiratory tract (LRT) and 5 external quality assessment program (EQAP) samples. The respiratory specimens were enrolled throughout the first two post-COVID-19 influenza seasons in Hong Kong (March to December 2023). For URT specimens, full concordance was observed between the SPOTFIRE R Panel and the standard-of-care FilmArray Respiratory 2.1 plus Panel (RP2.1plus) for 109 specimens (109/133, 81.95%). After discrepant analysis, the SPOTFIRE R Panel identified more pathogens than the RP2.1plus in 15 specimens and vice versa in 3 specimens. The per-target negative and positive percentage agreement (NPA and PPA) were 92.86-100% except the PPA of adenovirus (88.24%). For LRT and EQAP samples, all results were fully concordant. To conclude, the performance of the SPOTFIRE R Panel was comparable to the RP2.1plus.

Clinical Study of Flumazenil Antagonizing Remimazolam on Nausea and Vomiting After Gynecologic Day Surgery.

Purpose: To evaluate the effect of flumazenil antagonizing remimazolam on postoperative nausea and vomiting (PONV) after gynecologic day surgery. Patients and Methods: 141 cases of gynaecological daycase surgery patients in Weifang People's Hospital were selected, randomized into group F (flumazenil group, 71 cases) and group C (control group, 70 cases). Dexamethasone 5 mg, flurbiprofen axetil 50 mg, and droperidol 1 mg were given intravenously before induction of anesthesia in both groups. Anesthesia induction: Remimazolam 0.25mg / kg was injected within 1 minute. After the patient fell asleep, mivacurium chloride 0.2mg / kg was injected for 30 seconds and alfentanil 20ug / kg was injected for 30 seconds. Anesthesia maintenance: Remimazolam 1mg/kg/h and alfentanil 40ug/kg/h were continuously pumped by micro pump. Stopping the injection of remimazolam and alfentanil at the end of the operation. Flumazenil 0.2 mg was given to antagonize remimazolam in group F after 1 minute. Group C was given an equal volume of saline. The incidence of PONV in the postoperative PACU and over a 24-hour period, patient awakening time, and general patient information were recorded. Results: The incidence of PONV in both groups within 24 hours was 50.70% in group F was significantly higher than 32.86% in group C. The difference was statistically significant (P < 0.05). The incidence of PONV in the PACU was 5.6% in group F and 8.6% in group C. The difference was not statistically significant (p > 0.05). Conclusion: Flumazenil antagonism of remimazolam increases the incidence of PONV within 24 hours in gynecologic day surgery patients and has no significant effect on the incidence of PONV in the PACU.

The Seasonality of Respiratory Viruses in a Hong Kong Hospital, 2014-2023.

We reviewed the multiplex PCR results of 20,127 respiratory specimens tested in a hospital setting from January 2014 to April 2023. The seasonal oscillation patterns of 17 respiratory viruses were studied. Compared with 2014-2019, a prominent drop in PCR positivity (from 64.46-69.21% to 17.29-29.89%, p < 0.001) and virus diversity was observed during the COVID-19 pandemic, with predominance of rhinovirus/enterovirus, sporadic spikes of parainfluenza viruses 3 and 4, respiratory syncytial virus and SARS-CoV-2, and rare detection of influenza viruses, metapneumovirus, adenovirus and coronaviruses. The suppressed viruses appeared to regain activity from the fourth quarter of 2022 when pandemic interventions had been gradually relaxed in Hong Kong. With the co-circulation of SARS-CoV-2 and seasonal respiratory viruses, surveillance of their activity and an in-depth understanding of the clinical outcomes will provide valuable insights for improved public health measures and reducing disease burden.

[Expression and Prognostic Value of Cytokines in Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognostic value of cytokines in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). METHODS: Clinical data of 62 patients diagnosed with DLBCL in the First People's Hospital of Yunnan Province from June 2017 to November 2018 were collected. The differences in expression levels of 14 serum cytokines [interleukin (IL)-1ß, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, IL-17F, IL-22, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, TNF-ß] in patients with different survival outcomes, and the impact of the cytokines on 3-year progression-free survival (PFS) and 3-year overall survival (OS) of patients with DLBCL were analyzed retrospectively. RESULTS: Among the 14 cytokines, only the expression of IL-10 was significantly different in patients with different survival outcomes (P =0.007). According to the receiver operating characteristic (ROC) curve, the optimal cut-off value for IL-10 was 11.74 pg/ml. Serum IL-10 was positively correlated with infection markers procalcitonin (PCT) (r =0.321, P =0.029), C-reactive protein (CRP) (r =0.320, P =0.013) and tumor burden index lactate dehydrogenase (LDH) (r =0.439, P <0.001) in newly diagnosed DLBCL patients. The level of IL-10 in patients with pulmonary infection was significantly higher than that in patients without pulmonary infection (P =0.012). However, there was no statistically significant difference on the 3-year survival outcomes between patients with or without pulmonary infection. There was no significant difference in IL-10 level in patients with different Ann Arbor stages (P >0.05). Patients with high IL-10 level (IL-10>11.74 pg/ml) had significantly higher LDH level than those with low IL-10 level (IL-10≤11.74 pg/ml) (P <0.001). The 3-year PFS rate and 3-year OS rate of DLBCL patients with high IL-10 level were significantly lower than those of low IL-10 level group [(44.4±11.7)% vs (81.8±5.8)%, P <0.001; (61.6±11.5)% vs (93.2±3.8)%, P =0.001]. CONCLUSION: Serum IL-10 level in newly diagnosed DLBCL patients can reflect the inflammatory state of the body, which may be related to tumor load. Newly diagnosed DLBCL patients with serum IL-10>11.74 pg/ml have higher early mortality and worse prognosis.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion.

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.

Synchronously occurring endometrioid carcinomas of the uterine corpus and uterine cervix preceded by different precancerous lesions: A case study and a literature review.

The incidence of two synchronous carcinomas originating from the uterine corpus and uterine cervix, both endometrioid subtypes, is exceedingly rare. Herein, we presented synchronous early stage G1 adenocarcinoma of the uterine corpus with cervical G2 endometrioid adenocarcinoma. Although both neoplasms displayed the same histological subtype, they differed significantly according to the histological grading or clinical stage of the disease. Finally, it is worth emphasizing that both tumors were preceded by different precancerous lesions, atypical endometrial hyperplasia (AEH) and foci of endometriosis localized within the uterine cervix. Although AEH is a well-known precancerous condition of endometrioid carcinoma, the mechanisms resulting in the malignant transformation of endometriosis foci to the cervical endometrioid carcinoma are still a matter of controversy. We briefly summarized the impact of different precancerous lesions on the development of synchronous female genital tract neoplasms with the same histotype.

Study on the effectiveness and safety of ciprofol in anesthesia in gynecological day surgery: a randomized double-blind controlled study.

BACKGROUD: ciprofol is a new type of intravenous anesthetic, which is a tautomer of propofol, with the characteristics of less injection pain, less respiratory depression and higher potency, but little clinical experience. The aim of this study was to observe the efficacy and safety of the application of ciprofol in ambulatory surgery anesthesia in gynecology. METHODS: 128 patients were selected to undergo gynecological day surgery under general anesthesia, and the patients were randomly divided into the ciprofol group and the propofol group, with 64 cases in each group. During anesthesia induction, the ciprofol group was infused at a time limit of 0.5 mg/kg for one minute, and the propofol group was infused at a time limit of 2 mg/kg for 1 min. The overall incidence of adverse events was the primary outcome for this study, while secondary outcomes included the success rate of anesthesia induction, the time of loss of consciousness, the time of awakening,top-up dose and frequency of use of rescue drugs. RESULTS: The overall incidence of adverse events was significantly lower in the ciprofol group compared with the propofol group (56.2% vs. 92.2%,P < 0.05). The success rate of anesthesia induction of ciprofol and propofol group was 100.0%. The time of loss of consciousness of the ciprofol group was longer than that of the propofol group (1.6 ± 0.4 min vs. 1.4 ± 0.2 min, P < 0.05). The time of awakening was not statistically significant (5.4 ± 2.8 min vs. 4.6 ± 1.6 min, P > 0.05). The number of drug additions and resuscitation drugs used were not statistically significant. CONCLUSIONS: Compared with propofol, ciprofol had a similar anesthetic effect in gynecological ambulatory surgery, and the incidence of adverse events in the ciprofol group was lower.

Effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting in gynaecological day surgery under remimazolam-based general anesthesia.

BACKGROUND: To observe the effect of low-dose propofol combined with dexamethasone on the prevention of postoperative nausea and vomiting (PONV) in gynaecological day surgery under remimazolam-based general anesthesia. METHODS: A total of 120 patients, aged from 18 to 65 years old, American Society of Anesthesiologists grade I or II, were scheduled to undergo hysteroscopy under total intravenous anesthesia. The patients were divided into 3 groups (n = 40 each): dexamethasone plus saline group (DC group), dexamethasone plus droperidol group (DD group) and dexamethasone plus propofol group (DP group). Dexamethasone 5 mg and flurbiprofen axetil 50 mg were given intravenously before induction of general anesthesia. Anesthesia induction: remimazolam 6 mg/kg/hours was continuously pumped until sleep and slow intravenous injection of alfentanil 20 ug/kg and mivacurium chloride 0.2 mg/kg was given. Anesthesia maintenance: remimazolam 1 mg/kg/hour and alfentanil 40 ug/kg/hours were continuously pumped. After the start of surgery, DC group was given 2 mL saline, DD group was given droperidol 1 mg, and DP group was given propofol 20 mg. Primary outcome: incidence of PONV in the postanesthesia care unit (PACU). Secondary outcome: incidence of PONV in patients within 24 hours after surgery, as well as general patient data, duration of anesthesia, the recovery time of patients, dose of remimazolam and alfentanil, etc. RESULTS: In PACU, patients of group DD and DP showed less PONV than those in group DC (P < .05). Within 24 hours after operation, there was no significant difference in the incidence of PONV among the 3 groups (P > .05), but the incidence of vomiting in DD group and DP group was significantly lower than that in DC group (P < .05). There was no significant difference in general data, anesthesia time, the recovery time of patients and dosage of remimazolam and alfentanil among the 3 groups (P > .05). CONCLUSION: The effect of low-dose propofol combined with dexamethasone to prevent PONV under remimazolam-based general anesthesia was similar to that of droperidol combined with dexamethasone, both of which significantly reduced the incidence of PONV in the PACU compared to dexamethasone alone. However, low-dose propofol combined with dexamethasone had little effect on the incidence of PONV within 24 hours compared to dexamethasone alone and only reduced the incidence of postoperative vomiting in patients.

The most effective but largely ignored target for prostate cancer early detection and intervention.

Over the past two decades, the global efforts for the early detection and intervention of prostate cancer seem to have made significant progresses in the basic researches, but the clinic outcomes have been disappointing: (1) prostate cancer is still the most common non-cutaneous cancer in Europe in men, (2) the age-standardized prostate cancer rate has increased in nearly all Asian and African countries, (3) the proportion of advanced cancers at the diagnosis has increased to 8.2% from 3.9% in the USA, (4) the worldwide use of PSA testing and digital rectal examination have failed to reduce the prostate cancer mortality, and (5) there is still no effective preventive method to significantly reduce the development, invasion, and metastasis of prostate cancer… Together, these facts strongly suggest that the global efforts during the past appear to be not in a correlated target with markedly inconsistent basic research and clinic outcomes. The most likely cause for the inconsistence appears due to the fact that basic scientific studies are traditionally conducted on the cell lines and animal models, where it is impossible to completely reflect or replicate the in vivo status. Thus, we would like to propose the human prostate basal cell layer (PBCL) as "the most effective target for the early detection and intervention of prostate cancer". Our proposal is based on the morphologic, immunohistochemical and molecular evidence from our recent studies of normal and cancerous human prostate tissues with detailed clinic follow-up data. We believe that the human tissue-derived basic research data may provide a more realistic roadmap to guide the clinic practice and to avoid the potential misleading from in vitro and animal studies.

Prevention of postoperative nausea and vomiting after gynaecological day surgery under remimazolam general anesthesia: a randomized double-blind controlled study.

PURPOSE: To observe the effect of different antiemetic drugs for the prevention of postoperative nausea and vomiting (PONV) after gynaecological day surgery under remimazolam general anesthesia. METHODS: One hundred ninety-two patients were selected for gynaecological day surgery and randomly divided into three groups: droperidol group (DD group), tropisetron group (DT group) and control group (DC group). Flurbiprofen axetil 50 mg and dexamethasone 5 mg were given intravenously before induction of anesthesia, and 2 min later droperidol 1 mg was given intravenously to the DD group, tropisetron 5 mg to the DT group and saline (5 ml) to the DC group. Induction of anesthesia: remimazolam 6 mg/kg/h was continuously infused until sleep, mivacurium 0.2 mg/kg and alfentanil 20ug/kg were slowly pushed, 3 min later intubation was performed to control breathing. Maintenance of anesthesia: 40ug/kg/h of alfentanil, 1 mg/kg/h of remimazolam continuous infusion. After awakening and extubation, the patient was transferred to the PACU. PONV were recorded in the PACU and an electronic questionnaire was pushed 24 h after surgery. RESULTS: The incidence of PONV within the PACU was significantly lower in the DD (14.5%)and DT(26.7%) groups than in the DC(50%) group (p < 0.01), there was no significantly difference between the DT and DD groups. There were no significant difference in the incidence of PONV in 24 h after surgery between the three groups(DD:DT:DC = 44.5%:45.1%:63.8%,p > 0.05). CONCLUSIONS: Droperidol or tropisetron combined with dexamethasone is superior to dexamethasone alone for the prevention of PONV in the PACU after remimazolam combined with alfentanil anesthesia, with no significant difference in the incidence of PONV in 24 h after surgery.

Recent Advancements in Poor Graft Function Following Hematopoietic Stem Cell Transplantation.

Poor graft function (PGF) is a life-threatening complication that occurs after transplantation and has a poor prognosis. With the rapid development of haploidentical hematopoietic stem cell transplantation, the pathogenesis of PGF has become an important issue. Studies of the pathogenesis of PGF have resulted in some success in CD34+-selected stem cell boosting. Mesenchymal stem cells, N-acetyl-l-cysteine, and eltrombopag have also been investigated as therapeutic strategies for PGF. However, predicting and preventing PGF remains challenging. Here, we propose that the seed, soil, and insect theories of aplastic anemia also apply to PGF; CD34+ cells are compared to seeds; the bone marrow microenvironment to soil; and virus infection, iron overload, and donor-specific anti-human leukocyte antigen antibodies to insects. From this perspective, we summarize the available information on the common risk factors of PGF, focusing on its potential mechanism. In addition, the safety and efficacy of new strategies for treating PGF are discussed to provide a foundation for preventing and treating this complex clinical problem.

Three important short-chain fatty acids (SCFAs) attenuate the inflammatory response induced by 5-FU and maintain the integrity of intestinal mucosal tight junction.

BACKGROUND: 5-Fluorouracil (5-FU) is a used chemotherapy drug for cancer, and its main side effect is intestinal mucositis which causes chemotherapy to fail. It was known that short-chain fatty acids (SCFAs) can inhibit immune cell release of various proinflammatory factors and inhibit excessive intestinal inflammation. However, the inhibitory effect of SCFAs on 5-FU-induced intestinal mucositis is still unclear. RESULTS: To simulate the effects of SCFAs on immune and intestinal epithelial cells, the cells (THP-1 cells and Caco-2 cells) were pretreated with sodium acetate (NaAc), sodium propionate (NaPc) and sodium butyrate (NaB), then inflammation was induced by 5-FU. The expressions of reactive oxygen species (ROS), Beclin-1, LC3-II, NF-κB p65, NLRP3 inflammasome, proinflammatory/anti-inflammatory cytokines and mucosal tight junction proteins were determined. In our results, the three SCFAs could inhibit ROS expressions, NLRP3, Caspase-1, IL-1ß, IL-6, IL-18, Beclin-1 and LC3-II, when induced by 5-FU. In a 5-FU-induced chemoentermuctis mouse model, Lactobacillus rhamnoides can increase the concentrations of three SCFAs in faeces and increase the concentrations of IL-1ß, IL-6 and IgA in serum, and decrease the expressions of NLRP3 and IL-17 in spleen cells. The expressions of ZO-1 and Occludin in intestinal mucosa were significantly increased. CONCLUSIONS: These results indicated that the three SCFAs can effectively suppress the inflammation of THP-1 cells and Caco-2 cells and maintain tight junction integrity in intestinal mucosal epithelial cells.

Differences in community structure of gastrointestinal tract between Helicobacter pylori positive patients and negative patients with gastric cancer.

Gastric cancer is one of the most severe cancers, while the relationship between Helicobacter pylori (H. pylori) and gastric cancer are still in dispute, and little work has been done to explore the microbial diversity between H. pylori positive patients and negative patients. In the present work, a total of 43 gastric cancer patients and 10 healthy 53 participants were enrolled to compare the microbial differences in community structure in gastrointestinal tract between H. pylori positive patients and negative patients with gastric cancer. Our results indicated that the abundance and diversity of gastrointestinal microbiota was slight lower in gastric cancer patients than that in healthy participants especially in intestine, while the abundance of some potential pathogens, e.g. Streptococcus, Lactobacillus, Akkermansia and Halomones were higher in H. pylori positive patients than H. pylori negative patients. Therefore, our work suggests the various microbial diversity between H. pylori positive patients and H. pylori negative patients with gastric cancer, which contribute to deepen the understanding of the role of H. pylori in gastric carcinogenesis and progression.

Downregulation of miR-375 contributes to ERBB2-mediated VEGFA overexpression in esophageal cancer.

Esophageal cancer (EC) is a lethal cancer with an extremely aggressive nature and poor survival rate. However, the molecular mechanisms driving the occurrence and progression of EC are not well understood. MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of protein-coding genes. miRNA-mediated gene regulation plays an important role in EC. By cross-referencing studies from NCBI, we found that microRNA-375 (miR-375) is one of the most frequently downregulated miRNAs in EC. We assessed expression of miR-375 in EC cell lines and primary EC tissues and their matched normal tissues. We found significant downregulation of miR-375 in both cell lines and EC tissues. Forced expression of miR-375 attenuated EC cell proliferation and invasion. Human epidermal growth factor receptor 2 (HER2, ERBB2), a known proto-oncogene, was identified here as one of the potential target genes of miR-375. Ectopic expression of miR-375 significantly suppressed the expression of ERBB2 and subsequently downregulated one of its target genes, vascular endothelial growth factor A (VEGFA), which is related to cancer invasion and metastasis. These findings suggest that miR-375 acts as a tumor suppressor by blocking the ERBB2/VEGFA pathway with the potential to modulate the occurrence and/ or progression of EC.

Prospective Non-Randomized Study of Intraoperative Assessment of Surgical Resection Margin of Colo-Rectal Liver Metastases.

Introduction: More than 50% of patients with colorectal cancer (CRC) develop liver metastases during the natural course of disease. Surgical resection is currently the most potentially curative method in the treatment of colorectal liver metastases (CRLM). The goal of surgery is to achieve a negative resection margin (RM) of at least 1 mm, which provides the best prognosis for patients. The RM can be assessed by the pathologist of the resected liver specimen (RLS) and by the surgeon intraoperatively. The aim of this research paper is to determine the degree of agreement on intraoperative assessment of the RM by the surgeon and histopathological RM assessment by the pathologist. Material and methods: This prospective non-randomized double-blind study was approved by the Ethics Committee of the Oncology Institute of Vojvodina and registered on ClinicalTrials.gov #NCT04634526. The study was conducted at the Oncology Institute of Vojvodina, Sremska Kamenica, Serbia. An experienced hepatobiliary surgeon assessed RM for every specimen intra-operatively, immediately after CRLM resection. Resected CRLM lesions were analyzed by two experienced pathologists. These data were compared with pathological RM assessment as a "gold standard". RM of 1 mm or more was rated as negative RM (RM-). Disease-free survival (DFS) and recurrence rate was calculated by RM status defined by surgeon and by pathologist. Results: From 01 January 2015 to 31 August 2019, 98 patients were enrolled in the study. There were 219 RLS with 245 CRLM. The surgeon registered positive RM (RM+) of <1mm in 41 (18.7%) RLS. Taking the result of the histopathological assessment (HPA) as the "gold standard", it was determined that RM was true positive in 32 (14.6%) cases. False positive RM was found in 9 (4.1%) cases. False negative RM was found in 20 (9.1%) cases. True negative RM was found in 158 (72.2%) cases. Sensitivity of surgical assessment (SA) of RM+ was 61.5% (32/52). Specificity of SA of RM+ was 94.6% (158/167). The positive predictive value (PPV) was 78.0% (32/41), while the negative predictive value (NPV) was 88.8% (158/178). The overall accuracy of the RM+ SA was 86.8% (190/219). There was no statistically significant difference in the assessment of RM+ per RLS by surgeon and pathologists (p=0.061), but it was significant when analyses per patients was performed (p=0.017). Recurrence rate for RM+ patients was 48.1% (13/27, p=0.05) for SA and 35.0% (14/40, p=0.17) for HPA. Three year DFS for RM- and RM+ was 66.5% and 27.9% (p=0.04), respectively, by SA, and 64.8% and 42.1% (p=0.106), respectively, by HPA. Conclusion: Intraoperative assessment of RM- by surgeon of RLS is clinically meaningful. There is not a statistically significant difference in the assessment of RM+ by surgeon and pathologists per RLS, but it was statically significant on a per patient basis. RM determined by surgeon has better prognostic impact on recurrence rate and 1- and 3-year DFS than standard histopathological assessment.

A microfluidic colorimetric biosensor for in-field detection of Salmonella in fresh-cut vegetables using thiolated polystyrene microspheres, hose-based microvalve and smartphone imaging APP.

A microfluidic colorimetric biosensor was developed using thiolated polystyrene microspheres (SH-PSs) for aggregating of gold nanoparticles (AuNPs), a novel hose-based microvalve for controlling the flow direction, and a smartphone imaging APP for monitoring colorimetric signals. Aptamer-PS-cysteamine conjugates were used as detection probes and reacted with Salmonella in samples. Complementary DNA - magnetic nanoparticle (cDNA - MNP) conjugates were used as capture probes, reacted with the free aptamer-PS-cysteamine conjugates. AuNPs were aggregated on the surface of Salmonella-aptamer-PS-cysteamine conjugates, resulting in a visible color change in the detection chamber, which indicating different concentrations of Salmonella. The limit of detection was low to 6.0 × 101 cfu/mL. The microfluidic biosensor exhibited a good specificity. It was evaluated by analyzing salad samples spiked with Salmonella. The recoveries ranged from 91.68% to 113.76%, which indicated its potential application in real samples.

Hematopoietic Stem Cell Niche During Homeostasis, Malignancy, and Bone Marrow Transplantation.

Self-renewal and multidirectional differentiation of hematopoietic stem cells (HSCs) are strictly regulated by numerous cellular components and cytokines in the bone marrow (BM) microenvironment. Several cell types that regulate HSC niche have been identified, including both non-hematopoietic cells and HSC-derived cells. Specific changes in the niche composition can result in hematological malignancies. Furthermore, processes such as homing, proliferation, and differentiation of HSCs are strongly controlled by the BM niche and have been reported to be related to the success of hematopoietic stem cell transplantation (HSCT). Single-cell sequencing and in vivo imaging are powerful techniques to study BM microenvironment in hematological malignancies and after HSCT. In this review, we discuss how different components of the BM niche, particularly non-hematopoietic and hematopoietic cells, regulate normal hematopoiesis, and changes in the BM niche in leukemia and after HSCT. We believe that this comprehensive review will provide clues for further research on improving HSCT efficiency and exploring potential therapeutic targets for leukemia.

Traditional Chinese medicine compound, Bu Sheng Hui Yang Fang, promotes the proliferation of lymphocytes in the immunosuppressed mice potentially by upregulating IL-4 signaling.

The immune system plays a pivotal role in defending against infection and cancer immunosurveillance during the onset and procession of malignant disease. Cancer patients are frequently immunocompromised and subject to refractory infection and relapse of leukemia, due to the cytotoxic agents and immunosuppressive glucocorticoids in the chemotherapy regimens. Bu Shen Hui Yang Fang (BSHY), a traditional Chinese compound, was widely used in China to enhance the immune system of leukemia patients combined with chemotherapy and effectively lowered their risk of infection, with specific mechanism unknown yet. Thus, we investigated the effects of BSHY on the immune system using immunosuppressive mouse models. By analyzing the immune system of immunosuppressed BALB/C mice induced by hydrocortisone, we found an increase of CD4+ and CD8+ lymphocytes in the spleens of mice after BSHY treatment. Furthermore, we found the enhanced immune system in BSHY treated group was due to increased proliferation and decreased apoptosis of lymphocytes. Cytokine array analysis revealed that interleukin 4 (IL-4) was reduced in the plasma of immunosuppressed mice but returned to a normal level after BSHY treatment. Moreover, we found IL-4 was an adverse prognostic factor in acute myeloid leukemia patients and part of them could be elevated by BSHY. Mechanistically, we found BSHY enhances the proliferation of lymphocytes in a Stat6-dependent manner. In summary, our current study demonstrates that BSHY enhances the proliferation of lymphocytes in the immunosuppressed mice via upregulating IL-4 signaling.

Autism spectrum disorder screening in preschools.

LAY ABSTRACT: With professional training and regular opportunities to observe children interacting with their peers, preschool teachers are in a good position to notice children's autism spectrum disorder symptomatology. Yet even when a preschool teacher suspects that a child may have autism spectrum disorder, fear of false alarm may hold the teacher back from alerting the parents, let alone suggesting them to consider clinical assessment for the child. A valid and convenient screening tool can help preschool teachers make more informed and hence more confident judgment. We set out to develop a screening tool that capitalizes on peer interaction as a naturalistic "stress test" to identify children more likely than their peers to have autism spectrum disorder. A total of 304 3- to 4-year-olds were observed at school with an 84-item preliminary checklist; data-driven item reduction yielded a 13-item Classroom Observation Scale. The Classroom Observation Scale scores correlated significantly with Autism Diagnostic Observation Schedule-2 scores. To validate the scale, another 322 2- to 4-year-olds were screened using the Classroom Observation Scale. The screen-positive children and randomly selected typically developing peers were assessed for autism spectrum disorder 1.5 years later. The Classroom Observation Scale as used by teachers and researchers near preschool onset predicted autism spectrum disorder diagnoses 1.5 years later. This user-friendly 13-item Classroom Observation Scale enables teachers and healthcare workers with little or no clinical training to identify, with reliable and valid results, preschoolers more likely than their peers to have autism spectrum disorder.