Objective To compare the efficacy and safety of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) for the treatment of hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) advanced or metastatic breast cancer. Methods Randomized controlled trials (RCTs) on CDK4/6i for the treatment of HR+/HER2− metastatic or advanced breast cancer were retrieved from databases including PubMed, EMbase, Web of Science, The Cochrane Library, CNKI, Wanfang, VIP, and SinoMed, with the search period ranging from database inception to August 2023. Bayesian network meta-analysis was conducted using R 4.2.0 software. Results A total of 18 RCTs from 25 articles, involving 8 031 patients and 11 treatment regimens, were included. There was no significant difference in progression-free survival (PFS) or overall survival (OS) among different CDK4/6i+ET combinations. The highest cumulative probability for PFS was observed with dalpiciclib (DAL)+fulvestrant (FUL), while ribociclib (RIB)+FUL ranked first for OS. In terms of efficacy, abemaciclib (ABE)+aromatase inhibitors (AI) and ABE+FUL ranked first in objective response rate and clinical benefit rate, respectively. Regarding safety, statistically significant difference in grade 3-4 adverse events was observed among certain types of CDK4/6i (P<0.05). Conclusion Current evidence suggests that CDK4/6i+ET is superior to ET alone for the treatment of HR+/HER2− advanced/metastatic breast cancer. Different CDK4/6i+ET combinations demonstrate comparable or similar efficacy; however, the incidence of adverse reactions is higher with combination therapy. Treatment regimens should be selected based on individual conditions.

Objective To establish a sandwich enzyme-linked immunosorbent assay (ELISA) method for the quantitative detection of Chromogranin A (CHGA) in saliva, and to explore its preliminary application in the testing of saliva samples. Methods Recombinant human CHGA protein was used to immunize BALB/c mice, and monoclonal antibodies (mAbs) were prepared and screened using conventional hybridoma technology. A double-antibody sandwich ELISA detection method was constructed, and the matrix effect of saliva samples was optimized. This method was then applied to detect the concentration of CHGA in the saliva of stressed individuals. Results Twenty-one stable hybridoma cell lines secreting high affinity anti-human CHGA antibodies were obtained. A pair of detection antibodies with the best effect was selected, and the optimal coating concentration was determined to be 10 μg/mL, with the optimal dilution of detection antibodies being 1:32 000. The accuracy and reproducibility of this method were verified, with both intra-batch and inter-batch variation coefficients less than 15×, and the recovery rate between 80× and 120×. The matrix effect was further optimized to make it suitable for saliva sample detection. Saliva samples from individuals in different stress states were collected, and the CHGA levels were detected using the method established in this study, indicating its potential to reflect the intensity of stress. Conclusion A reliable saliva CHGA ELISA detection method has been successfully established, and its potential as a biomarker in stress-related research has been preliminarily explored.
Saliva/metabolism* ; Enzyme-Linked Immunosorbent Assay/methods* ; Humans ; Animals ; Mice, Inbred BALB C ; Mice ; Chromogranin A/immunology* ; Antibodies, Monoclonal/immunology* ; Female ; Male ; Reproducibility of Results ; Adult

Coronavirus-related diseases pose a significant challenge to the global health system. Given the diversity of coronaviruses and the unpredictable nature of disease outbreaks, the traditional "one bug, one drug" paradigm struggles to address the growing number of emerging crises. Therefore, there is an urgent need for therapeutic agents with broad-spectrum anti-coronavirus activity. Here, we provide evidence that ATV006, an anti-SARS-CoV-2 nucleoside analog targeting RNA-dependent RNA polymerase (RdRp), has broad antiviral activity against human and animal coronaviruses. Using mouse hepatitis virus (MHV) and human coronavirus NL63 (HCoV-NL63) as a model, we show that ATV006 has potent prophylactic and therapeutic activity against murine coronavirus infection in vivo. Remarkably, ATV006 successfully inhibits viral replication in mice even when administered 96 h after infection. Due to its oral bioavailability and potency against multiple coronaviruses, ATV006 has the potential to become a useful antiviral agent against SARS-CoV-2 and other circulating and emerging coronaviruses in humans and animals.

The regulatory processes in developmental biology research are significantly influenced by long non-coding RNAs (lncRNAs). However, the dynamics of lncRNA expression during human tooth development remain poorly understood. In this research, we examined the lncRNAs present in the dental epithelium (DE) and dental mesenchyme (DM) at the late bud, cap, and early bell stages of human fetal tooth development through bulk RNA sequencing. Developmental regulators co-expressed with neighboring lncRNAs were significantly enriched in odontogenesis. Specific lncRNAs expressed in the DE and DM, such as PANCR, MIR205HG, DLX6-AS1, and DNM3OS, were identified through a combination of bulk RNA sequencing and single-cell analysis. Further subcluster analysis revealed lncRNAs specifically expressed in important regions of the tooth germ, such as the inner enamel epithelium and coronal dental papilla (CDP). Functionally, we demonstrated that CDP-specific DLX6-AS1 enhanced odontoblastic differentiation in human tooth germ mesenchymal cells and dental pulp stem cells. These findings suggest that lncRNAs could serve as valuable cell markers for tooth development and potential therapeutic targets for tooth regeneration.
Humans ; RNA, Long Noncoding/metabolism* ; Odontogenesis/genetics* ; Tooth Germ/embryology* ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Mesoderm/metabolism* ; Tooth/embryology* ; Gene Expression Profiling ; Sequence Analysis, RNA ; Dental Pulp/cytology*

Objective To analyze the prevalence, annual trends, and co-morbidity trends of common chronic diseases among workers in a large automotive industry from 2019 to 2021, and to provide a scientific basis for the health management of workers in the automotive industry. Methods The health examination data of workers in a large automotive industry from 2019-2021 were analyzed. Trends in the prevalence of chronic diseases and co-morbidities were analyzed using Join Point software and trend χ² test. Results The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in the 2019 – 2021 health checkups of workers in this enterprise increased at an average rate of 9.27%, 11.35%, and 3.99% per year, respectively. The prevalence of metabolic syndrome, hyperuricemia, and fatty liver in male workers showed an increasing trend at an average rate of 7.05%, 9.25%, and 2.91% per year, respectively. The prevalence of metabolic syndrome in female workers showed an increasing trend at an average rate of 20.76% per year. The prevalence of metabolic syndrome, hyperuricemia and fatty liver was on the rise in the age groups ≤ 29 years old and 40 – 49 years old. The proportion of metabolic syndrome and its co-morbidity with one or two common chronic diseases showed an increasing trend. Conclusion The prevalence and co-morbidity of common chronic diseases in this enterprise are generally on the rise. The enterprise should focus on health education and preventive care for chronic diseases among workers aged ≤ 29 and 40 – 49 years old and male workers and control the annual increasing trend of metabolic syndrome among female workers and workers in the age group ≤ 29 years.

OBJECTIVE To analyze the MSCT and MRI imaging manifestations of patients with duplication of the internal auditory canal(DIAC),improve understanding of the deformity,to provide preoperative basis for cochlear implantation.METHODS Retrospective observation of 20 cases(24 ears)of DIAC inner ear multi-spiral CT(MSCT)and MRI data,measurement and analysis of the width of the internal auditory canal(IAC)and cochlear nerve canal in the lesion group and the control group.RESULTS All DIACs had stenosis of the IAC cambined with other temporal bone malformations.MSCT shows that the 21 ears IAC,while MRI hydrography shows the 16 ears IAC divided into double tubes by bone.MRI hydrography shows a slender vestibulocochlear nerve.There were statistically significant differences(P<0.001)in the width of IAC and cochlear nerve canal between the lesion group and the control group.Six cases(8 ears)had varying degrees of hearing recovery after cochlear implant surgery.CONCLUSION DIAC shows stenosis of the IAC;The bone septa shown on MSCT are its characteristic fertures;MRI hydrography shows underdeveloped vestibular and cochlear nerves;The combination of two imaging examination methods can provide objective reference for the diagnosis of this disease and artificial auditory implantation.

BACKGROUND:A large number of previous studies have confirmed that a high concentration of metabolites is significantly correlated with embryo quality and clinical outcome,and the theory of silencing embryo development indicates that normally developed embryos maintain a low level of material exchange with the outside world during in vitro culture,while embryos often show abnormal metabolic activity due to stress repair mechanism when DNA damage occurs. OBJECTIVE:To establish and verify an embryo quality prediction model based on the third-day 340 nm absorbance embryo cultures to provide the basis for a more objective and accurate embryo quality assessment. METHODS:269 patients at the Nanxishan Hospital of Guangxi Zhuang Autonomous Region for in vitro fertilization and embryo transplantation from November 2019 to December 2021 were retrospectively analyzed.Among them,on day 3,162 cases who had 873 optimal embryos and 214 high-quality blastocysts were included in the high-quality embryo group.On day 3,107 cases who had 859 non-optimal embryos and 214 non-high-quality blastocysts were included in the non-high-quality embryo group.Lambert-beer law was used to screen out the characteristic wavelength with distinguishing degree between superior and non-superior embryos,analyze its correlation and influence trend with high-quality embryos,and establish the clinical prediction model and validation of absorbance for high-quality and non-high-quality embryos at this wavelength. RESULTS AND CONCLUSION:(1)There was a significant difference in absorbance between high-quality and non-high-quality embryos at 340 nm on day 3(P<0.001),and a negative correlation was found with the formation of high-quality embryos on day 3(r=-0.486,P<0.001).The absorbance of high-quality and non-high-quality blastocyst at 340 nm was significantly different(P<0.05),and was negatively correlated with the formation of high-quality blastocyst(r=-0.642,P<0.001).(2)The optimal cut-off value of absorbance at 340 nm between high-quality and non-high-quality embryos on day 3 was 0.235.The area under the curve was 0.799.Sensitivity was 62.9%.Specificity was 78.0%.Accuracy was 70.5%.The optimum cutoff value of high-quality and non-high-quality blastocysts of absorbance at 340 nm was 0.175.The area under the curve was 0.871.Sensitivity was 74.3%.Specificity was 89.1%.Accuracy was 82.2%.(3)Restricted cubic spline curve analysis showed that when the absorbance of the culture medium at 340 nm was greater than 0.221,there was a significant positive trend on the formation of non-high-quality embryos at day 3,and when the absorbance of the culture medium at 340 nm was greater than 0.160,there was a significant positive trend on the formation of non-high-quality blastocysts.(4)The clinical decision curve and clinical influence curve showed that the absorbance of the culture medium at 340 nm had the maximum clinical net benefit for the prediction models of high-quality embryos and high-quality blastocysts on the third day when the valve probability was 0.18-0.95 and 0.16-1.00,respectively,and the ratio of loss to gain within the valve probability range was always less than 1.It is proven that the prediction model has good efficacy in clinical applications.The results of embryo transfer showed that the absorbance of embryo culture medium at 340 nm in non-pregnant patients was significantly higher than that in clinical pregnancy,biochemical pregnancy and early abortion patients(P<0.05).(5)The high-quality and non-high-quality embryo culture in 340 nm absorbance has a significant difference with correlation.The embryo quality prediction model has a certain clinical value and application effectiveness.The joint embryo morphology evaluation to a certain extent improves the objectivity and accuracy of embryo quality evaluation.

Objective To investigate the effect of miR-130a targeting phosphase and tensin homology deleted on chromosome ten(PTEN)/phosphoinositide 3 kinase(PI3K)/protein kinase B(AKT)pathway on renal tissuecell apoptosis in diabetic kidney disease(DKD)rats.Methods The DKD rat model was constructed by feeding high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).72 rats were divided into normal control group(NC),DKD model group(DKD),miR-130a agonist negative control group(NC agomir),and miR-130a agonist group(miR-130a agomir),miR-130a agomir+ PTEN overexpression negative control group(miR-130a agomir+pcDNA),and miR-130a agomir+ PCDNA-PTEN overexpression group(miR-130a Agomir + PCDNA-PTEN),with12 rats in each group.Urinary microalbumin kit was used to detect 24 h urine albumin(UAlb).Fasting blood glucose(FBG),serum creatinine(Scr)and blood urea nitrogen(BUN)were detected by automatic biochemical analyzer.Pathological changes of renal tissue were detected by HE staining.The levels of serum IL-6 and TNF-α were detected by ELISA.The apoptosis of renal tissue was detected by TUNEL staining.The expression of miR-130a was detected by qRT-PCR,and the expression of B-cell lymphoma-2-associated X protein(Bax),B-cell lymphoma-2(Bcl-2)and PTEN/PI3K/AKT pathway were detected by Western blot.Dual luciferase reporter gene experiment was used to verify the targeting relationship between miR-130a and PTEN.Results Compared with DKD and NC agomir groups,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression in miR-130a agomir group were decreased(P＜0.05).The expressions of miR-130a,Bcl-2,p-Akt/AKT protein were increased(P＜0.05).Compared with miR-130a agomir group,24 h UAlb,FPG,Scr,BUN,IL-6,TNF-α,renal cell apoptosis rate,Bax protein expression and PTEN protein expression were increased in miR-130a agomir+pcDNA-PTEN group(P＜0.05).The expression of Bcl-2,p-Akt/AKT protein decreased(P＜0.05).Conclusion Overexpression of miR-130a may inhibit renal cell apoptosis in DKD rats by down-regulating PTEN to activate PI3K/AKT pathway.

Objective:To construct an evaluation index system for the core competence of infection control link nurses.Methods:With the core competence theory as the guiding framework, the literature research method, and the expert meeting method preliminarily drew up the index item pool. After two rounds of expert consultation, the evaluation index of the core competence of infection control link nurses was determined.Results:Two rounds of expert inquiry were conducted, with 23 and 22 questionnaires distributed, respectively. A total of 22 and 20 valid questionnaires were collected, with effective response rates of 95.65% and 90.91%, respectively. The expert authority coefficients were 0.92 and 0.91, respectively. Kendall's harmony coefficients for the overall indicator importance and operability evaluation in the second round of expert inquiry were 0.191 and 0.230, respectively (both P<0.01). Finally, the evaluation index system of infection control link nurses consisted of five primary indexes and 43 secondary indexes. Conclusions:The evaluation index system for core competence of infection control link nurses constructed in this study is scientific, reliable, and practical, which can provide a reference for the training and evaluation of infection control link nurses.

Objective:To review the current research and existing problems of symptom cluster sentinel symptoms in cancer patients both domestically and internationally, so as to provide reference for future research.Methods:The literature on sentinel symptoms of cancer symptom clusters, from the establishment of the database until November 8, 2023, was electronically searched on platforms such as China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Database, PubMed, Web of Science, Cochrane Library, Embase and so on. Descriptive statistical analysis was conducted.Results:Sixteen articles were included, with an overall upward trend in publication volume, including 10 Chinese articles and 6 English articles. The sentinel symptom hotspots of cancer patients' symptom clusters mainly included: (1) the number of symptoms included in the analyzed symptom clusters was 3 to 13, the number of symptom clusters was 1 to 8, and the number of sentinel symptoms explored in each literature was 1 to 8; (2) Identification and dynamic changes of sentinel symptoms in symptom clusters; (3) Differences in sentinel symptoms among different symptom groups of cancer patients; (4) Analyzing specific sentinel symptoms of symptom groups based on different statistical methods; (5) Intervention based on sentinel symptoms of symptom clusters.Conclusions:In recent years, the symptom cluster sentinel symptoms of cancer patients have received attention from researchers at home and abroad, but there are problems such as uneven development and inconsistent research methods. High quality identification research is needed to make the included population specific and the methods scientifically unified, and to focus on the impact and mechanism of symptom cluster sentinel symptoms on patient outcomes in symptom clusters, so as to investigate potential mechanisms and promote effective symptom management.