As an important aminoglycosides antibiotic, gentamicin has been used clinically over decades. With the development in modern biological technology, the mechanisms of gentamicin action and resistance, its biosynthesis and structural modification were studied in great depth. Meanwhile, its emerging novel bioactivities and potential applications are also under extensive exploration. Here we summarize the latest progresses and prospects towards the future development of gentamicin for more efficient and effective uses.
Aminoglycosides ; biosynthesis ; chemistry ; Gentamicins ; biosynthesis ; chemistry

BACKGROUNDKAI1 is a new identified metastasis-suppressor gene whose expression in many types of tumors has been reported. The aim of study is to investigate the role of KAI1 protein in development of lung cancer and its values in predicting the prognosis of lung cancer.

METHODSThe expressions of KAI1 protein were detected in benign pulmonary disease tissue, precancerous disease tissue, lung cancer tissue and metastatic lung cancer tissue in local lymph node using tissue microarray and immunohistochemical method. The relationship between expression of KAI1 protein and clinicopathological parameters of patients with lung cancer was analyzed by Chi-Square test and Fisher exact test.

RESULTSThe positive rate of KAI1 expression was 100.0% in 10 cases of benign pulmonary diseases, 66.7% in 12 cases of precancerous diseases, 24.7% in 89 cases of primary lung cancer and 0 in metastatic lung cancer tissue in local lymph node respectively. The KAI1 protein expression in primary lung cancer tissues had no remarkable relationship with age and gender of the patients and the location of cancer, but had significant relationship with the histological type and differentiated degree of tumor, P-TNM stages and lymph node metastatic status.

CONCLUSIONSThe abnormal expression of KAI1 protein may participate in malignant progression of lung cancer. Its downregulation may promote the invasion and metastasis of tumor cell. Detection of the expression of KAI1 protein may be helpful to predict the prognosis of lung cancer.

BACKGROUNDIt has been proved that EphB4 and HIF-1α are closely related to the oncogenesis and development of lung cancer. The aim of this study is to investigate the biological significances of EphB4 and HIF-1α in lung cancer and their relationship with each other.

METHODSThe expression of EphB4 and HIF-1α was detected in 54 lung cancer tissues and 10 normal lung tissues as control by immunohistochemical method.

RESULTSEphB4 and HIF-1α proteins were detectable in 50.0% and 42.6% of all 54 lung cancer tissues respectively, which were significantly higher than those of the control (P < 0.05); the positive ratios and the levels of the expressions of EphB4 and HIF-1α proteins were closely related to gross types, differentiations and clinical stages (P < 0.05), but not to histological classification, age, sex and lymph node metastasis (P > 0.05). A highly positive correlation was observed between EphB4 and HIF-1α expression (P < 0.01 ).

CONCLUSIONSOverexpression of EphB4 and HIF-1α may play an important role in the pathogenesis, progression and malignant degree of lung cancer. Detection of EphB4 and HIF-1α expression might be helpful to predict prognosis of patients with lung cancer.

Objective:To investigate the effect of peer support-based narrative therapy on postoperative self-image and stigma of patients with head and neck cancer, to provide reference for clinical nursing.Methods:A total of 78 head and neck cancer patients from August 2018 to August 2020 in Fudan University Shanghai Cancer Center were divided into experimental group and control group by random digits table method, each group were 39 cases. The control group was given conventional nursing, while the experimental group implemented support-based narrative therapy on the basis of routine nursing. The intervention time was 4 weeks. The self-image and stigma of the two groups before and after intervention were assessed by Body Image Scale (BIS) and Social Impact Scale (SIS), respectively.Results:Finally, 37 cases were included in the experimental group and 38 cases in the control group. There was no significant difference in BIS, SIS dimension scores and total scores between the two groups before intervention ( P>0.05). After intervention, the emotional demension scores, behavior dimension scores, cognitive dimension scores and total scores in BIS were 4.41 ± 1.04, 1.95 ± 0.51, 3.81 ± 0.63 and 10.16 ± 2.05 in the experimental group, significantly lower than in the control group 5.08 ± 1.08, 2.82 ± 0.60, 5.42 ± 0.76 and 13.32 ± 1.93, the differences were statistically significant ( t values were 2.76-6.86, all P<0.01); the social exclusion scores, internal shame scores, social isolation scores and total stigma scores in SIS were 17.57 ± 2.67, 9.08 ± 1.55, 12.14 ± 3.73 and 46.14 ± 4.95 in the experimental group, significantly lower than in the control group 19.18 ± 3.70, 10.68 ± 1.61, 14.18 ± 3.83 and 51.68 ± 6.09, the differences were statistically significant ( t values were 2.16-4.38, all P<0.05). Conclusions:Peer support-based narrative therapy can effectively alleviate the postoperative self-image problems and stigma of patients with head and neck cancer, which is worthy of clinical application.

Objective:To analyze the epidemiological characteristics of etiology from patients with hand, foot and mouth disease(HFMD) in ji’an of Jiangxi from 2013 to 2020, and provide effective prevention and control measures for the diagnosis and treatment of HFMD in the region.Methods:We collected 5089 stool and other clinical specimens from patients with HFMD. Fluorescence quantitative PCR was used for enterovirus detection and typing, SAS statistical software was used to analyze the epidemiological characteristics of pathogens from the types of specimens, time, age, gender, and regional distribution.Results:A total of 3 062 positive samples for enterovirus (EV) were detected out of 5 089 samples, with a total positive rate of 60.17%. The proportions of EV71, CoxA16 and other enteroviruses were 15.15%, 16.36% and 68.49%, and other enterovirus infections were the main ones; the positive rate of enterovirus showed a downward trend from 2013 to 2020; the difference in the positive rate of enterovirus in different years was statistically significant ( χ2=118.47, P<0.05). In the past 8 years, the EV71 type of HFMD in Ji’an showed a downward trend year by year. The number of positive cases was mainly concentrated in April-November, with the peak around May and September. There was no significant difference in the positive detection rate between male and female ( χ2=3.44, P>0.05). The positive rate of stool, anal swab and herpes fluid was higher than that of throat swab, and the difference was significant ( χ2=78.76, P<0.01). Conclusions:In recent years, the surveillance result showed that the pathogenic spectrum of enterovirus had changed in Ji’an, relevant surveillance should be carried out according to the actual situation of HFMD etiology in this region, which is conducive to the prevention and control of HFMD in this region.

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Objective To investigate the effects of dexmedetomidine(Dex)on osteoporosis(OP)rats and possible mechanisms.Methods The rats were divided into sham operation group,osteoporosis model group(OP,replica-ting the OP rat model with bilateral ovariectomies),Dex-L,M,and H(Dex low,medium,and high dose treat-ments)groups and Dex-H+XAV-939 group(Wnt/β-catenin pathway inhibitor).Micro-CT was applied to meas-ure bone mineral density(BMD)and bone microstructure of rat femurs.The three-point bending experiment was applied to analyze the biomechanics of the femur(maximum load,fracture deflection,elastic modulus).HE stai-ning was applied to observe pathological changes in the femur of rats.ELISA method was applied to evaluate bone metabolism indicators such as alkaline phosphatase(ALP),typeⅠ procollagen amino-terminal peptide(PINP)and typeⅠcollagen cross-linked C-telopeptide(CTX-Ⅰ).The expression of Runx2 and Wnt3a was examined by Immunohistochemistry.Western blot was applied to detect the protein expression of Runx2 and Wnt3a/β-catenin pathway in femoral tissue.Results Compared to the Sham group,the bone volume and number of trabeculae in OP group were obviously reduced,the maximum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased,CTX-Ⅰ increased(P＜0.05).Compared to the OP group,the bone trabecular structure in the Dex-L,M,and H groups was restored,the maxi-mum load,fracture deflection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression all increased but CTX-Ⅰ decreased(P＜0.05).Compared to the Dex-H group,the bone trabecular injury in the Dex-H+XAV-939 group showed a more severe damage.The maximum load,fracture de-flection,elastic modulus,BMD,Tb.Th,Tb.N,BV/TV,ALP,PINP,Runx2,Wnt3a,β-catenin expression decreased while CTX-Ⅰ increased(P＜0.05).Conclusions Dex may antagonize OP effects by improving bone density,biomechanical properties and microstructure.The underlying mechanism might be related to the activation of the Wnt/β-catenin signaling pathway.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Background::Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in Shenzhen.Methods::This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and analyzed.Results::Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q 1-Q 3: 24.0-34.0 years); of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) only. Conclusions::Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote HIV-preventive strategies in the MSM population. The extremely high prevalence of TDR mutation in this population implies the need for future pretreatment drug resistance surveillance.

Mesp family proteins comprise two members named mesodermal posterior 1 (Mesp1) and mesodermal posterior 2 (Mesp2). Both Mesp1 and Mesp2 are transcription factors and they share an almost identical basic helix-loop-helix motif. They have been shown to play critical regulating roles in mammalian heart and somite development. Mesp1 sits in the core of the complicated regulatory network for generation of cardiovascular progenitors while Mesp2 is central for somitogenesis. Here we summarize the similarities and differences in their molecular functions during mammalian early mesodermal development and discuss possible future research directions for further study of the functions of Mesp1 and Mesp2. A comprehensive knowledge of molecular functions of Mesp family proteins will eventually help us better understand mammalian heart development and somitogenesis as well as improve the production of specific cell types from pluripotent stem cells for future regenerative therapies.
Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors ; genetics ; Cell Differentiation ; genetics ; Gene Expression Regulation, Developmental ; Mesoderm ; embryology ; metabolism ; Mice, Knockout ; Molecular Sequence Data ; Pluripotent Stem Cells ; metabolism ; Sequence Homology, Amino Acid