Objective To verify the accuracy of γ spectrometry by analyzing the results of national interlaboratory comparisons of radionuclide analysis by γ spectrometry from 2018 to 2023. Methods A statistical analysis was conducted on the results from multiple years of participation in the national interlaboratory comparisons of radionuclide analysis by γ spectrometry. The measurement results of radionuclide specific activities in soil were analyzed to provide technical support for improving the capability to analyze radionuclides in soil. Results The laboratory participated in six interlaboratory comparisons and conducted 23 radionuclide analyses by γ spectrometry from 2018 to 2023. The relative deviation was −12.20% to 8.11%, the |Z_test| was 0 to 0.61, the U_test was 0 to 0.62, and the U_rel was 0.07 to 0.12. The overall pass rate was 100% and the excellent rate was 33.3%. In addition, 21 of the 23 (91.3%) radionuclide analyses showed full scores in experiment operation. However, the total scores were relatively low due to multiple oversights and lack of rigor in the preparation of the test reports, which prevented the laboratory from qualifying for the excellence evaluation process, resulting in a relatively low excellent rate. Conclusion The interlaboratory comparisons indicate that the measurements of radionuclides in this laboratory were all qualified, with full scores for experiment operation in several analyses. These results demonstrate that the soil radionuclide analysis system based on γ spectrometry is reliable and stable.

Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To explore the application and potential optimization of the collaborative and competitive learning model in the Health Education course. Methods:Undergraduate medical students participating in Health Education course practice tasks were selected to conduct discussions and reach consensus according to research objectives based on the e fast anonymous consensus-forming tool (eFAST). The meeting records were analyzed for theme identification using the keyword classification method. Results:Nine medical students participated in eFAST discussions. The students considered the following five aspects as the most important for undertaking Health Education course practice tasks using the collaborative and competitive learning model: timely communication, problem evaluation, report content enrichment, reasonable task allocation within groups, and task topic selection by group members together. They also proposed suggestions on improvement of the assessment method, including teacher involvement in scoring, intra-group scoring based on inter-group scoring, all students participating in inter-group scoring, and using mobile applications for scoring and summarization. Conclusions:The collaborative and competitive learning model can be used in the teaching of Health Education, but further optimization is needed in course task design, implementation, reporting, and assessment.

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment landscape for chronic myeloid leukemia (CML). However, TKI resistance poses a significant challenge, leading to treatment failure and disease progression. Resistance mechanisms include both BCR::ABL1-dependent and BCR::ABL1-independent pathways. The mechanisms underlying BCR::ABL1 independence remain incompletely understood, with CML cells potentially activating alternative signaling pathways, including the AKT/mTOR and JAK2/STAT5 pathways, to compensate for the loss of BCR::ABL1 kinase activity. This study explored tumoral VISTA (encoded by VSIR) as a contributing factor to TKI resistance in CML patients and identified elevated tumoral VISTA levels as a marker of resistance and poor survival. Through in vitro and in vivo analyses, we demonstrated that VSIR knockdown and the application of NSC-622608, a novel VISTA inhibitor, significantly impeded CML cell proliferation and induced apoptosis by attenuating the AKT/ mTOR and JAK2/STAT5 pathways, which are crucial for CML cell survival independent of BCR::ABL1 kinase activity. Moreover, VSIR overexpression promoted TKI resistance in CML cells. Importantly, the synergistic effect of NSC-622608 with TKIs offers a potent therapeutic avenue against both imatinib-sensitive and imatinib-resistant CML cells, including those harboring the challenging T315I mutation. Our findings highlight the role of tumoral VISTA in mediating TKI resistance in CML, suggesting that inhibition of VISTA, particularly in combination with TKIs, is an innovative approach to enhancing treatment outcomes in CML patients, irrespective of BCR::ABL1 mutation status. This study not only identified a new pathway contributing to TKI resistance but also revealed the possibility of targeting tumoral VISTA as a means of overcoming this significant clinical challenge.

OBJECTIVE: To explore the characteristics of copy number variation (CNV) within the Y chromosome azoospermia factor (AZF) region in patients with spermatogenesis disorders in the Shenzhen area. METHODS: A total of 123 patients with spermatogenesis disorders who had visited Shenzhen People's Hospital from January 2016 to October 2022 (including 73 patients with azoospermia and 50 patients with oligozoospermia) and 100 normal semen males were selected as the study subjects. The AZF region was detected with multiplex ligation-dependent probe amplification (MLPA), and the correlation between the CNV in the AZF region and spermatogenesis disorders was analyzed using the chi-square test or Fisher's exact test. RESULTS: 19 CNV were detected among 53 patients from the 223 samples, including 20 cases (27.40%, 20/73) from the azoospermia group, 19 cases (38%, 19/50) from the oligozoospermia group, and 14 cases (14%, 14/100) from the normal control group. In the azoospermia, oligozoospermia, and normal control groups, the detection rates for CNV related to the AZFa region (including AZFab and AZFabc) were 5.48% (4/73), 2.00% (1/50), and 0 (0/100), respectively. The detection rates for the AZFb region (including the AZFbc region) were 6.85% (5/73), 0 (0/50), and 0 (0/100), respectively. The detection rates for gr/gr deletions in the AZFc region were 2.74% (2/73), 6.00% (3/50), and 9.00% (9/100), respectively, and those for b2/b4 deletions in the AZFc region were 2.74% (2/73), 10.00% (5/50), and 0 (0/100), respectively. The detection rates for complex rearrangements in the AZFc region were 6.85% (5/73), 18.00% (9/50), and 3.00% (3/100), respectively. Statistical analysis showed no significant difference in the detection rate of gr/gr deletions between the three groups (Fisher's Exact Test value = 2.712, P = 0.249); the differences in the detection rate of b2/b4 deletions between the three groups were statistically significant (Fisher's Exact Test value = 9.489, P = 0.002); the differences in the detection rate of complex rearrangements in the AZFc region between the three groups were statistically significant (Fisher's Exact Test value = 9.493, P = 0.006). In this study, a rare AZFa region ARSLP1 gene deletion (involving SY86 deletion) was detected in a patient with oligozoospermia. CONCLUSION CNV in the AZFa and AZFb regions have a severe impact on spermatogenesis, but partial deletion in the AZFa region (ARSLP1 gene deletion) has a minor impact on spermatogenesis. The b2/b4 deletion and complex rearrangement in the AZFc region may be risk factors for male infertility. The gr/gr deletion may not serve as a risk factor for male infertility in the Shenzhen area.
Humans ; Male ; Azoospermia/genetics* ; DNA Copy Number Variations ; Oligospermia/genetics* ; Infertility, Male/genetics* ; Y Chromosome

The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin (DOX)-loaded methoxy polyethylene glycol-polycaprolactone (mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration; DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

Objective:To study the effect of Sanjie Xiaoliu Recipe on transplanted tumors in breast cancer mice through in vivo experiments, in order to explore the efficacy and mechanism of Sanjie Xiaoliu Recipe on breast cancer patients. Methods:45 BaL B/c female mice were selected to establish the transplanted tumor model of breast cancer. All the transplanted tumor models of breast cancer mice were randomly divided into five groups: the control group (intragastric administration of normal saline), the low, medium and high dose group of Sanjie Xiaoliu Recipe (intragastric administration of different doses of Sanjie Xiaoliu Decoction), and the paclitaxel group (intraperitoneal injection of paclitaxel). After 24 days of continuous administration, the diet and activities of mice were observed; the body weight, weight and volume changes of transplanted tumor mice were recorded, and the tumor inhibition rate was calculated. Western blot was used to detect the expression of epithelial mesenchymal transformation related proteins (E-cadherin, N-cadherin, Vimentin) in the transplanted tumor tissues of mice in each group.Results:(1) The food intake and activity status of mice treated with Sanjie Xiaoliu Recipe were less affected by the transplanted tumor of breast cancer. (2) The volume and weight of transplanted tumor in the treat groups were smaller than those in the control group (all P<0.01), and the volume of transplanted tumor in the middle dose group of Sanjie Xiaoliu Recipe was smaller than that in the low dose group ( P<0.05). The tumor inhibition rates among the treatment groups were: Sanjie Xiaoliu Recipe medium dose group 52.4%, paclitaxel group 40.3%, Sanjie Xiaoliu Recipe low dose group 39.5%, Sanjie Xiaoliu Recipe high dose group 34.1%. (3) The results of Western blot showed that the expression level of E-cadherin in the transplanted tumor tissue of the treat groups was higher than that in the control group, and the expression levels of N-cadherin and Vimentin were lower than that in the control group, with statistically significant difference (all P<0.05). Conclusions:The Sanjie Xiaoliu Recipe can improve the weakness and reduced consumption of breast cancer mice, which can inhibit the tumor mass growth in mice to a certain extent. Its mechanism may be that Sanjie Xiaoliu Recipe can inhibit the epithelial mesenchymal transformation of breast cancer and the invasion and metastasis of breast cancer.

Dyslipidemia is an important risk factor of atherosclerotic cardiovascular disease (ASCVD). Statins delay the occurrence and development of ASCVD, and reduce the risk of cardiovascular events and death. Due to safety concerns, there exist insufficient use of lipid-lowering agents and a high withdrawal rate of the agents in the elderly. To promote the prevention and treatment of ASCVD, this expert consensus is issued and focuses on the management of dyslipidemia of Chinese elderly basing on the clinical evidence of the use of lipid-lowering drugs by the elderly, and the lipid management guidelines and expert consensus recommendations at home and abroad.

ObjectiveTo evaluate the current situation of human resource allocation in district and county centers for disease control and prevention （CDCs） in Kashgar ， identify existing problems and influencing factors， and to provide scientific evidence for optimizing the human resource allocation. MethodsA survey was conducted among all CDCs in Kashgar in February 2022. The questionnaire included the institutional and individual questions. ResultsThe overall staff size approved for the CDCs in Kashgar was 604， with a staffing rate of 76.17%， among which the staffing rates in 5 county CDCs were less than 60%. Currently， there were a total of 524 approved staff members in all CDCs， resulting in a vacancy rate of 13.25%. In the district CDC， 85 staff members were on duty， while the median of staff on duty was 34 in each county CDC. The staff in the district CDC was ageing， of which those aged over 45 accounted for 67.06%. The staff in the county CDCs was generally young， of which those aged less than 35 accounted for 54.22%. Moreover， the proportion of staff with bachelor’s degree or above in the district and county CDCs was 31.76% and 24.95%， respectively. The proportion of staff without professional title was 32.94% and 48.03%， respectively. In contrast， the proportion of those with middle and senior professional title was 57.89% and 22.02%， respectively. In addition， in recent 3 years， 24 staff members resigned in the CDCs， all of whom had professional titles. ConclusionHuman resources are insufficient in CDCs in Kashgar. Furthermore， staff structure is unreasonable， with a serious loss of human resources. In particular， the district CDC needs to optimize the allocation of human resources.