[A multicenter study on effect of delayed chemotherapy on prognosis of Burkitt lymphoma in children].

Objective: To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis. Methods: Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups. Results: Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old (OR=0.54,95%CI 0.30-0.93), tumor lysis syndrome before chemotherapy (OR=0.48,95%CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy (OR=0.55,95%CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions: The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

[Interim efficacy of a multicenter cohort study for China Net Childhood Lymphoma mature B-cell lymphoma 2017 regimen in the treatment of pediatric High-grade-B cell lymphoma].

Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageⅡ, 33(53.2%)patients in stage Ⅲ and 18(29.1%)patients in stage Ⅳ. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 regimen in the treatment of pediatric Burkitt lymphoma].

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ2=4.16, P=0.041) and group C2 (χ2=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ2=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.

GSDME Is Related to Prognosis and Response to Chemotherapy in Oral Cancer.

Gasdermin E (GSDME), as the major executive protein of pyroptosis, has been considered to be linked to antitumor immunity in recent years. However, the role of GSDME in oral squamous cell carcinoma (OSCC) remains to be elucidated. Here, by using a human OSCC tissue microarray, human OSCC tissue, and Tgfbr1/Pten conditional knockout mice, we found that GSDME was strongly expressed in OSCC and that GSDME expression in primary tumors was higher than that in metastatic lymph nodes. In addition, GSDME expression in OSCC was positively related to better prognosis. Moreover, GSDME-mediated pyroptosis occurred upon stimulation with chemotherapy drugs, and functional knockdown of GSDME attenuated the cisplatin-induced antitumor effect. Consistent with these results, bioinformatic analysis indicated that GSDME expression was positively correlated with the sensitivity of a number of antitumor drugs approved by the US Food and Drug Administration. Inhibition of GSDME expression by small interfering RNA in SCC7 cells significantly increased the expression of the cancer stem cell markers, CD44 and ALDH1. Furthermore, multiplexed immunohistochemistry and flow cytometry indicated that the expression of GSDME positively correlated with tumor-infiltrating CD8+ T cells, granzyme B, and M1 phenotype macrophages. Collectively, these findings demonstrated that GSDME is a potential positive prognostic factor of OSCC, and GSDME-mediated pyroptosis induced by chemotherapy plays a role in antitumor response.

[Evaluation of the perioperative period and long-term outcomes of minimally invasive LTE and minimally invasive CTLE esophagectomy for stage â -â ¢ cervical esophageal carcinoma based on propensity score matching analysis].

Objective: To evaluate the perioperative period and long-term effects of minimally invasive gasless laparoscopic transhiatal esophagectomy (LTE) and minimally invasive combined thoracoscopic and laparoscopic esophagectomy (CTLE) for stageⅠ-Ⅲ cervical esophageal cancer. Methods: The clinical data of 158 consecutive patients with cervical esophageal cancer stageⅠto Ⅲ who underwent minimally invasive CTLE or LTE esophagectomy in the Department of Thoracic Surgery, Beijing Tongren Hospital from January 2008 to December 2019 were retrospectively analyzed. A total of 40 pairs of cases were matched (40 cases of CTLE and 40 cases of LTE surgery) after using the propensity score matching analysis which aimed to balance the influence of confounding factors between groups, including 43 males and 37 females, aged 51 to 81 (62.5±7.0) years old. The perioperative variables and long-term outcomes of the two groups were compared. Results: The operation time ((148.0±31.3) min vs (201.3±48.3) min), intraoperative blood loss ((192.6±77.9) ml vs (387.8±112.4) ml), ICU monitoring time (0 day vs 1 day), and the complication rates of postoperative pneumonia (0 vs 15%) and arrhythmia (2.5% vs 20%) were lower in the LTE group than that of in the CTLE group(all P<0.05). The number of lymph node dissections in the CTLE group was higher than that of in the LTE group (21.2±6.1 vs 12.9±4.3, P<0.001). The 3-and 5-year overall survival (OS) rate and disease-free survival (DFS) rate in the LTE group (OS: 53.53% and 34.27%, DFS: 43.62% and 24.89%, respectively) and the CTLE group (OS: 59.48% and 37.29%, DFS: 49.12% and 28.82%, respectively) had no statistical differences (all P>0.05). Conclusion: The LTE group has advantages in reducing operation time, intraoperative bleeding, ICU monitoring time, postoperative incidence of pneumonia and arrhythmia, and its long-term prognosis is comparable to that of the CTLE group.

[Evaluation of infrahepatic inferior vena cava clamping in robot-assisted laparoscopic liver resection].

Objective: To evalutate the safety and efficacy of infrahepatic inferior vena cava clamping robot-assisted laparoscopic liver resection. Methods: All data about 24 patients with robotic liver resection at Hepatic Surgery Center,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology between February 2015 and December 2017 were collected and analyzed. These patients were divided into two groups based on different methods to decrease central venous pressure. Eight patients(6 males and 2 females,aged 49 years(range:50 to 56 years)) were applied with infrahepatic inferior vena cava clamping,and the other 16 matched cases (15 males and 1 female,aged 53 years(range:38 to 69 years)) were categorized into lowering central venous pressure group. Intraoperative blood loss,blood transfusion,intraoperative hemodynamic parameters,postoperative complications,and renal function were compared by t-test,non-parametric test,χ2 test,or Fisher exact test. Results: There was significantly difference in the intraoperative blood loss between the infrahepatic vena cava clamping group and the lowering central venous group(200(220) ml (range:100 to 400 ml) vs. 750(800) ml (range:100 to 2 000 ml),Z=‒2.169,P=0.030). The clamping time of portal triad and infrahepatic inferior vena cava were 24 (18) minutes and 29 (20) minutes in the infrahepatic inferior vena cava clamping group, and portal triad clamping time was 23 (23) minutes in the low central venous group. There was no significant difference between the two groups (Z=‒0.323, P=0.747). There was no intraoperative blood transfusion in the infrahepatic inferior vena cava clamping group, and 5 cases in the low central venous group, with a transfusion volume of 1.5(1.5)U. The difference between the two groups was statistically significant (Z=‒3.353, P=0.001). However, the mean arterial pressure in the infrahepatic vena cava clamping group decreased from (88.6±4.9) mmHg to (67.4±3.8) mmHg(1 mmHg=0.133 kPa), which was lower than that of lowering central venous group (72.4±3.3) mmHg (t=2.315,P=0.003). And there were no significant differences related to postoperative complications rate or hepatic and renal function in both groups. Conclusion: The infrahepatic inferior vena cava technology is safe and feasible to decrease central venous pressure during robotic liver resections,which will not affect the recovery of hepatic and renal functions.

Short communication: Influence of intramuscular injection of vitamin B12 in early-lactation dairy cows on Mozzarella cheese quality and vitamin B12 stability.

The current study explored the effect of intramuscular injection of vitamin B12 (VB12) in early-lactation dairy cows on subsequent low-moisture part-skim Mozzarella cheese quality and VB12 levels during cheese processing and storage. Twenty-four peripartum dairy cows were blocked based on parity and milk yield and randomly assigned into 2 treatments: basal diet (CON) and basal diet with an intramuscular injection of 10 mg of VB12 per cow per week (VB12). Raw milk was collected to determine VB12 content and then used to make low-moisture part-skim Mozzarella cheese 8 wk after injection. The VB12 content of raw milk and cheese was determined using ultra-performance liquid chromatography coupled with tandem mass spectrometry. We found that VB12 content was significantly increased in milk (15.43 vs. 3.30 ng/mL) and fresh cheese (3.72 ng/g vs. undetectable) from the VB12 group compared with the CON group. However, approximately 70% of VB12 was lost in the whey during cheese making, and no VB12 was detectable in either cheese treatment after 8 wk of storage. Furthermore, no significant differences were observed in fat and protein contents in the cheese between the 2 groups. For cheese color, the b* value increased and the a* value decreased slightly in fresh VB12 cheese. Functional properties of stretchability, flowability, and meltability of VB12 cheese were initially comparable to that of CON cheese, but higher flowability and meltability was observed in VB12 cheese after 8 wk of storage. In summary, intramuscular injection of VB12 in early-lactation dairy cows increases the content of VB12 in milk and fresh cheese with no adverse effect on cheese quality, but substantial VB12 is lost during cheesemaking and declines rapidly during storage.

LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer, by W.-D. Zhao, B.-X. Zhang, X.-H. Cui, J. Zhang, N. Du, Y.-F. Zhang, published in Eur Rev Med Pharmacol Sci 2019; 23 (13): 5815-5822-DOI: 10.26355/eurrev_201907_18320-PMID: 31298333" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/18320.

[Consideration on improving public health emergency management ability of current medical health system].

COVID-19 is a Public Health Emergency of International Concern (PHEIC). Direct economic loss is expected to be much more than that of SARS outbreak in 2003. The risk factors of COVID-19 epidemic at the early stage included the misjudgment of the epidemic, delay in reporting this emerging infectious disease, nosocomial infection-caused transmission of the virus into local communities, and weak public health interventions. The infection rate (or the incidence) reflects the prophylactic effect in population. Case fatality reflects the therapeutic effect of clinical intervention. There were sufficient medical resources at the national top levels accumulated in Wuhan. Furthermore, medical professionals and sufficient medical supplies from other provinces have been assigned to join in the fighting against the epidemic in Wuhan. However, the case fatality in Wuhan has been kept the highest in China, indicating that clinical treatment for this virus-caused emerging infectious disease, whose pathogenesis remains to be elucidated, with limited effect in controlling this epidemic. The unusual, extremely costly public health interventions including the temporarily city quarantine and transportation ban issued by the central government are crucial in controlling this epidemic. The control of epidemic indicates the importance of public health measures but also reflected its insufficient capacity in China. Recently, profit-seeking mechanism run in Chinese health service system disorganized the balance of clinical service and public health service patterns in China, promoting the vicious circle of "attaching importance to clinical treatment and despising disease prophylaxis" , damaging the infrastructure of public health capacity, thus contributing to the formation of the inevitability in various fortuities of public health emergency. To strength the capacity of our medical service system to respond to public health emergency efficiently, two key issues should be considered. First, public health service, which should be fixed as the health section of the governments' public services by the law, must be greatly improved to meet the increasing health needs of the publics. Second, the vicious circle of profit-seeking-caused "attaching importance to clinical treatment and despising disease prophylaxis" should be immediately broken to optimize the national health service system in China by increasing the investment in public health service.

[Recommendations for general surgery clinical practice in 2019 coronavirus disease situation].

The 2019 coronavirus disease(COVID-19) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the COVID-19 as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight against COVID-19.

[Recommendations for general surgery clinical practice in novel coronavirus pneumonia situation].

Novel coronavirus pneumonia (NCP) is a highly infectious disease, has a long incubation period and a variety of clinical manifestations, which has a significant impact on public health and life. Afterwards, scientific and standardized work processing during the epidemic is of great significance for prevention and control. In order to implement the central government's decision-making deployment and defeat the NCP as soon as possible, we had focused on the key points in the clinical work of general surgery according to latest relevant guidelines, literature and experience in epidemic prevention. Finally, we drafted the prevention and control strategies and recommendations to make a reference for medical staff of general surgery to fight NCP.

MicroRNA-148a regulates the MAPK/ERK signaling pathway and suppresses the development of esophagus squamous cell carcinoma via targeting MAP3K9.

OBJECTIVE: Esophagus squamous cell carcinoma (ESCC) was a dominant histological type of esophagus cancer, which has a very high incidence due to distant metastasis and local invasion. MicroRNA-148a (miR-148a) functioned as a tumor suppressor in a variety of cancers. The purpose of our study was to explore the vital role of miR-148a in esophagus squamous cell carcinoma. PATIENTS AND METHODS: The Kaplan-Meier method was applied to calculate the 5-year overall survival of esophagus squamous cell carcinoma patients. Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) and Western blot were conducted to calculate the mRNA levels of miR-148a and genes. The cell counting kit-8 (CCK-8) and transwell assays were performed to measure the proliferative and invasive ability. RESULTS: MiR-148a was observed to be significantly downregulated and the downregulation of miR-148 predicted poor prognosis of esophagus squamous cell carcinoma patients. MAP3K9 was a target gene of miR-148a and its expression was mediated by miR-148a through directly binding to the 3'-untranslated region (3'-UTR) of its mRNA in the esophagus squamous cell carcinoma. Moreover, miR-148a remarkably inhibited the proliferation and invasion through directly targeting to MAP3K9 via extracellular-signal-regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and epithelial-mesenchymal transition (EMT) in the ESCC cells. In addition, overexpression of miR-148a inhibited the growth of ESCC in vivo. CONCLUSIONS: MiR-148a inhibited the proliferation and invasion through directly targeting to MAP3K9 by ERK/MAPK pathway and EMT in ESCC cells. The newly identified miR-148a/MAP3K9 axis provides a novel insight into the pathogenesis of the esophagus squamous cell carcinoma.

LncRNA AB073614 promotes tumor migration and invasion by repressing CDKN1A in non-small cell lung cancer.

OBJECTIVE: Some researches have showed that long noncoding RNAs (lncRNAs) take part in varieties of biological behaviors during the tumor progression. This study aims to determine whether lncRNA AB073614 functioned in the metastasis of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to detect AB073614 expression in NSCLC tissues. Besides, wound healing assay and transwell assay were conducted in NSCLC cells. Furthermore, the mechanism assays were performed to identify how AB073614 functioned in metastasis of NSCLC cells. RESULTS: By comparing with the expression level in adjacent tissues, the AB073614 expression level in NSCLC samples was significantly higher. Moreover, after AB073614 was knocked down, invasion and migration of NSCLC cells were inhibited. And after AB073614 was overexpressed, invasion and migration of NSCLC cells were promoted. Also, mRNA and protein expression level of CDKN1A was upregulated via knockdown of AB073614, while mRNA and protein expression level of CDKN1A was downregulated via overexpression of AB073614. Besides, the expression of CDKN1A in NSCLC tissues was negatively correlated to the expression of AB073614. CONCLUSIONS: Our results indicated that AB073614 could enhance cell migration and cell invasion in NSCLC through repressing CDKN1A, which might offer a potential therapeutic choice for patients with NSCLC.

[Determination of 8-methoxypsoralen in mouse plasma by high performance liquid chromatography and its application to pharmacokinetic study].

OBJECTIVE: To establish a high performance liquid chromatography (HPLC) method for the determination of 8-methoxypsoralen (8-MOP) in mouse plasma and apply it to a pharmacokinetic study of 8-MOP. METHODS: 8-MOP was separated on a Waters Symmetry18 column (250 mm × 4.6 mm, 5 µm) and determined by HPLC using isocratic elution, and 5-methoxypsoralen was used as internal standard. The mobile phase consisted of methanol-water (55:45, V/V) at a flow rate of 1.0 mL/min. The excitation and emission wavelength of fluorescence detector were set at 334 nm and 484 nm respectively, and the internal standard method was used for quantitative analysis. In the study, 60 healthy ICR male mice were randomly divided into twelve groups. The mice in control group were administered intragastrically with 1% Tween 80, and the mice in the other eleven groups were administered intragastrically with 8-MOP (40 mg/kg). Plasma concentrations of 8-MOP in the mice at different time points after treatment were determined by HPLC. Pharmacokinetic parameters were calculated by DAS 2.0 software. RESULTS: The calibration curve of 8-MOP was linear with a correlation coefficient of 0.999 3 over the concentration range of 0.05 to 10 mg/L, and the limit of detection was 0.015 mg/L. The average recoveries of 8? MOP at three different concentrations (0.10, 0.50, 2.5 mg/L) were from 92.5% to 100.6%. The intra-day precision of 8-MOP was from 3.3% to 8.2%, while the inter-day precision was from 3.4% to 6.7% at three spiked concentration levels. The extraction recoveries of 8-MOP were from 90.9% to 92.0%, and the plasma samples could be stored at -80°C for 15 days at least at three spiked concentration levels. 8-MOP could be detected in mouse plasma 5 min after intragastrical administration to the mice (1.4 mg/L). The concentration of 8-MOP in the mouse plasma reached a maximum 2 h after administration, and 8-MOP could still be detected 24 h after administration (1.1 mg/L). t1/2 was (39.21±3.65) h, Cmax was (2.31±0.02) mg/L, tmax was (2.00±0.00) h, and AUC0-t was (33.34±1.19) (h×mg)/L. CONCLUSION: The proposed method is accurate and simple,suitable for pharmacokinetics of 8-MOP in mice.

Effect of dietary supplements of biotin, intramuscular injections of vitamin B12, or both on postpartum lactation performance in multiparous dairy cows.

The current study was conducted to investigate the effects of dietary supplementation of biotin, intramuscular injections of vitamin B12 (VB12), or both beginning at the prepartum period on feed intake and lactation performance in postpartum dairy cows. Forty-eight dairy cows were allocated into 12 blocks, based on parity and milk yield of the previous lactation cycle, and randomly assigned to 1 of 4 treatments. Supplementation of VB12 (weekly intramuscular injections of 0 or 10 mg) and biotin (dietary supplements of 0 or 30 mg/d) were used in a 2 × 2 factorial arrangement in a randomized complete block design of 12 blocks with repeated measures. The study started at 3 wk before the expected calving date and ended at 8 wk after calving. Feed intake and lactation performance (milk yield and composition) were recorded weekly after calving. Blood variables were measured on d -10, 0, 8, 15, 29, 43, and 57 relative to calving. When VB12 was given, the cows had greater feed intake, better lactation performance and lower body weight loss in the postpartum period compared with animals without injection of VB12. The VB12-injected cows had lower plasma nonesterified fatty acids and ß-hydroxybutyrate concentrations but higher plasma superoxide dismutase activity compared with cows without VB12. Cows fed a biotin supplement had higher milk protein yield (6 and 8 wk) and lactose yield (6-8 wk), compared with animals without biotin. However, under the present experimental conditions, we found no additive effect of a combined supplement of biotin and vitamin B12 on lactation performance of dairy cows.

Short communication: Effects of dietary 5,6-dimethylbenzimidazole supplementation on vitamin B12 supply, lactation performance, and energy balance in dairy cows during the transition period and early lactation.

The current study was conducted to investigate the effects of 5,6-dimethylbenzimidazole (DMB) supplementation to the feed during the transition period and early lactation on the vitamin B12 supply, lactation performance, and energy balance in postpartum cows. Twenty-four prepartum Holstein dairy cows were divided into 12 blocks based on their parity and milk yield at the last lactation and were then randomly allocated to 1 of 2 treatments: a basal diet without DMB (control) or a treatment diet that contained 1.5 g of DMB/d per cow. The study started at wk 3 before the expected calving day and ended at wk 8 postpartum. The feed intake and the lactation performance were measured weekly after calving. Blood parameters were measured on d -10, 0, 8, 15, 29, 43, and 57 relative to the calving day. Body weight was measured on the calving day and on d 57 after calving. The yields of milk, protein, and lactose in cows fed DMB were higher than in the control throughout the whole postpartum stage. On wk 8 postpartum, the vitamin B12 content in the milk and sera was greater in cows fed DMB than in the control. The overall body weight loss from wk 1 to 8 postpartum was less in cows fed DMB than in the control. The plasma content of nonesterified fatty acids and ß-hydroxybutyric acid was significantly lower in cows fed DMB than in the control throughout the whole experimental stage. In conclusion, dietary DMB fed during the transition period and early lactation improved the vitamin B12 supply, milk production, and energy balance of postpartum dairy cows.

A novel frameshift mutation of Chediak-Higashi syndrome and treatment in the accelerated phase.

Chediak-Higashi syndrome (CHS) is a rare autosomal recessive immunodeficiency disease characterized by frequent infections, hypopigmentation, progressive neurologic deterioration and hemophagocytic lymphohistiocytosis (HLH), known as the accelerated phase. There is little experience in the accelerated phase of CHS treatment worldwide. Here, we present a case of a 9-month-old boy with continuous high fever, hypopigmentation of the skin, enlarged lymph nodes, hepatosplenomegaly and lung infection. He was diagnosed with CHS by gene sequencing, and had entered the accelerated phase. After 8 weeks of therapy, the boy had remission and was prepared for allogenic stem cell transplantation.

An insufficient glucose supply causes reduced lactose synthesis in lactating dairy cows fed rice straw instead of alfalfa hay.

The objective of the present study was to investigate the nutrient availability for milk production in the mammary gland of lactating cows fed different forage-based diets. The 3 diets contained 30% corn stover (CS), 30% rice straw (RS), or 23% alfalfa hay plus 7% Chinese wild rye hay (AH) as a forage source. All diets contained 15% of DM as corn silage and 55% of DM as concentrate. The percentage of milk lactose was always lower in the RS-fed cows than in the cows fed AH or CS during the 12-wk feeding trial ( < 0.01). Ruminal propionate concentrations were lower in the RS group than in the AH group ( = 0.03). The ratio of insulin to glucagon in the mammary venous plasma was greater in the AH group than in the CS or RS group ( = 0.04). The abundance of the pyruvate carboxylase mRNA in the liver was lower in the RS group than in the AH or CS group ( = 0.04), and the abundance of mitochondrial phosphoenolpyruvate carboxykinase, IGF-1 receptor, and phosphofructokinase-liver, phosphofructokinase-muscle, and phosphofructokinase-platelet mRNA in the liver were lower in the RS group than in the AH group ( < 0.05). The mammary glucose uptake was greater in the AH-fed cows than in the CS- or RS-fed cows ( = 0.02). The mRNA abundance of the glucose transporters in the mammary gland was similar among the 3 treatments. The mRNA abundance of α-lactalbumin in the mammary gland of the cows fed RS tended to be greater compared with that of the cows fed AH or CS. The milk potassium concentration was greater in the cows fed RS than those fed AH or CS ( < 0.01). In summary, the insufficient ruminal propionate concentrations in the cows fed RS were associated with lower gluconeogenesis in the liver, resulting in the shortage of glucose supply for mammary utilization.