BACKGROUND:It has been shown that Gushukang affects bone metabolism by regulating nucleotide and amino acid metabolism and immune mechanisms.Current research on the mechanism of Gushukang in the treatment of osteoporosis primarily focuses on osteoblast regulation and requires further improvement from the perspective of osteoclasts. OBJECTIVE:To investigate the mechanism by which Gushukang interferes with osteoclasts in the treatment of osteoporosis using RAW264.7 cells as the research model. METHODS:Twenty-four 8-week-old female Sprague-Dawley rats were randomly divided into four groups(n=6 per group):the three experimental groups were given 1,2 and 4 g/kg osteoporosis solution by gavage(2 times per day),and the control group was given an equal amount of distilled water by gavage(2 times per day).After 7 days of intragastric administration,aortic blood samples were extracted to collect serum samples using centrifugation,and serum samples from the same groups were combined to obtain the low-,medium-,and high-concentration Gushukang-containing and normal sera for the subsequent experiments.(1)RAW264.7 cells were cultured in six groups:normal serum was added to the control group;low,medium,and high concentration groups were added with low,medium,and high concentrations of Gushukang-containing serum,respectively;ML385,a nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor was given in the Nrf2 inhibitor group;and t-BHQ,a Nrf2 activator,was added in the Nrf2 activator group.Cell viability was detected using the cell counting kit-8 assay.(2)The 3rd generation RAW 264.7 cells were cultured and divided into five groups:the blank control group was added with normal serum,the osteoclast group was added with receptor activator of nuclear factor κB ligand(RANKL),and the low-,medium-,and high-concentration groups were added with low-,medium-,and high-concentration Gushukang-containing serum based on the addition of RANKL.Tartrate-resistant acid phosphate staining was performed after 5 days of culture.(3)RAW264.7 cells were cultured and divided into five groups:blank control group was cultured with normal serum,osteoclast group cultured with normal serum and RANKL,high concentration+osteoclast group cultured with RANKL+high concentration Gushukang-containing serum,osteoclast+Nrf2 agonist group cultured with RANKL+t-BHQ,and high concentration+osteoclast+Nrf2 inhibitor group cultured with RANKL+high concentration Gushukang-containing serum+ML385.Western blot assay and determination of reactive oxygen content were performed after 5 days of culture. RESULTS AND CONCLUSION:The cell counting kit-8 results indicated that Gushukang-containing serum,NRF2 inhibitor or agonist had no significant effect on RAW264.7 cell viability.Tartrate-resistant acid phosphate staining results demonstrated that Gushukang-containing serum exhibited a concentration-dependent inhibitory effect on osteoclast differentiation.Western blot analysis and determination of reactive oxygen species revealed that compared with the blank control group,Nrf2 protein expression was decreased in the osteoclast group(P<0.05),while c-Fos and NFATc1 protein expression and reactive oxygen species content were elevated(P<0.05);compared with the osteoclast group,Nrf2 protein expression was elevated and reactive oxygen species content was decreased in the high-concentration+osteoclast group,osteoclast+Nrf2 agonist group,and high-concentration+osteoclast+Nrf2 inhibitor group(P<0.05),while c-Fos and NFATc1 protein expression was decreased in the high concentration+osteoclast group and osteoclast+Nrf2 agonist group(P<0.05);compared with the high concentration+osteoclast group,Nrf2 protein expression was decreased(P<0.05)and reactive oxygen species content was elevated(P<0.05)in the high concentration+osteoclast+Nrf2 inhibitor group.To conclude,Gushukang reduces reactive oxygen species production by activating Nrf2,thereby inhibiting downstream of the c-Fos/NFATc1 pathway and suppressing osteoclast differentiation.

BACKGROUND:Several observational studies have found a close relationship between thyroid function levels and sarcopenia,but the causal relationship between thyroid function levels and the onset of sarcopenia is not yet clear. OBJECTIVE:To investigate the causal relationship between thyroid function levels and sarcopenia using a two sample Mendelian randomization method. METHODS:A two sample Mendelian randomization analysis was conducted using genome-wide association study data on thyrotropin,free triiodothyronine,free tetraiodothyronine,subclinical hyperthyroidism,subclinical hypothyroidism,and four related phenotypes of sarcopenia-lefthand grip strength,right hand grip strength,limb lean mass,and gait speed.The inverse-variance weighted method,weighted median method,simple mode method,weighted median estimator method,and MR Egger regression method were used as analysis methods,while heterogeneity test,pleiotropy test,MR-PRESSO,leave-one-out method,funnel plot and other methods were used for sensitivity analysis. RESULTS AND CONCLUSION:Elevated levels of thyroid-stimulating hormone increased left-(β=0.02,SE=0.01,P=0.01)and right-handed grip strength(β=0.02,SE=0.01,P=0.01),an increase in free triiodothyronine decreased left-(β=-0.06,SE=0.02,P=9.5×10-5)and right-handed grip strength(β=-0.07,SE=0.02,P=9.3×10-5),and subclinical hyperthyroidism decreased gait speed(β=-4.4×10-3,SE=1.7×10-3,P=0.01).The sensitivity analysis results were basically consistent with the main analysis results.To conclude,an increase in thyroid-stimulating hormone is a protective factor for sarcopenia,and elevation of free triiodothyronine and subclinical hyperthyroidism may increase the risk of sarcopenia.

Lung cancer is characterized by high incidence and mortality rates and invasiveness, and its occurrence and development are influenced by various factors. Mitochondria, as ubiquitous organelles in the human body, regulate cellular processes, such as metabolism, signal transduction, oxidative stress, and genomic instability, thereby affecting the initiation and progression of lung cancer. This article summarizes the recent research progress on mitochondrial-targeted drugs, mitochondrial transfer, and mitochondrial gene therapy for lung cancer treatment. This work also discusses the principles and prospects of mitochondrial therapy to provide new insights for lung cancer treatment.

Red culture embodies the spirit and character of the Communist Party of China of continuous struggle and indomitable for more than 100 years,and is an important resource to promote the construction of academic style in colleges and universities.Red culture is of great help in strengthening the ideals and beliefs of medical students,improving medical ethics and self-cultivation,and cultivating professional spirit.However,the current integration of red culture into the construction of academic style has problems,such as the backwardness of teachers'media literacy,outdated educational discourse,and weak awareness of collaborative education.Based on these,colleges and universities should optimize the integration mechanism of red culture and academic style construction through innovative methods of publicity and education,changing educational discourse,expanding educational channels,and other methods.They should fully leverage the role of red culture in cultivating the foundation and solidifying the soul,enlightening wisdom and infiltrating the heart,and inspiring the fighting spirit.A vibrant and upward academic style should be actively created,as well as excellent academic style should be used to guide people's paths,nourish people's hearts,and urge people to make progress.

Osteosarcoma is the most common primary malignant bone tumor, yet treatment modalities and patient outcomes have remained relatively stagnant over the past three decades. Recently, with increasing insights into the molecular characteristics of osteosarcoma, targeted therapies, such as tyrosine kinase inhibitors and cell cycle-related inhibitors, have shown significant progress in both preclinical studies and clinical trials. Checkpoint kinase 1 (CHEK1), a key player in DNA damage response, is involved in various critical biological functions, and the development of its specific inhibitors has gained attention in multiple fields of cancer treatment. Osteosarcoma, comprising multiple subtypes with distinct alterations in cell cycle and DNA damage response mechanisms, particularly exhibits increased sensitivity to CHEK1 inhibitors in p53 mutant cells. Targeting the CHEK1-associated pathway holds promise for improving patient outcomes. Inhibition of ataxia telangiectasia mutated (ATM) and/or ataxia telangiectasia and Rad3-related (ATR) pathways impairs DNA damage repair in osteosarcoma cells, identifying downstream molecules linked to CHEK1 as potential therapeutic targets. Suppression of CHEK1 activity leads to downregulation of related protein expression and inhibits cell proliferation and repair processes, an effect that is notably enhanced when combined with chemotherapeutic agents. Although single-agent chemotherapy often produces limited results, the use of CHEK1 inhibitors such as Prexasertib enhances cytotoxic effects against osteosarcoma cells, either as monotherapy or in combination regimens, demonstrating robust efficacy. Co-administration of CHEK1 inhibitors with other cell cycle modulators or downstream target antagonists could further optimize treatment outcomes. Furthermore, modulating DNA damage response pathways may have implications for immunotherapy. This review systematically summarizes recent research on the CHEK1-related pathway in osteosarcoma and emphasizes that targeting the DNA damage response pathway related to CHEK1 may be a promising strategy for osteosarcoma treatment with broad prospects.

Objective:To explore the effectiveness of applet-assisted teaching in the pedagogy of stomatology and gain suggestions for the improvement of the applet.Methods:Using digital technology, we built a professional atlas applet for Oral Histopathology that covered a wide range of contents including illustrations, histological slides, schematic diagrams, and hand-drawn pictures of knowledge points. Based on the WeChat platform, the applet had the functions of bilingual (Chinese/English) annotation and real-time interactive communication between teachers and students. Thirty dental students were given quizzes before and after using the atlas applet. The scores were analyzed using the t-test with SPSS 22.0 software. At the same time, 45 students filled a questionnaire after using the applet for one month, which involved comments on the use of the digital atlas, the degree of satisfaction and suggestions for the applet during learning, and suggestions for its co-use by teachers and students in the future. Results:After using the atlas applet to assist with learning, the test scores of the students were improved significantly in all domains. There were significant differences between the test and control groups in the score of completion questions [(17.00±2.61) vs. (15.03±1.85), P<0.05], the score of identification of images [(27.93±5.08) vs. (25.13±3.31), P<0.05], and the total score [(78.77±8.59) vs. (72.90±6.08), P<0.05]. The questionnaire feedback showed that the students were highly satisfied with the atlas applet-assisted learning, the function of teacher-student interaction, and the overall performance of the applet. Conclusion:An atlas is one of the crucial teaching tools of Oral Histopathology for its intuitionistic and realistic presentation of tissue structures, which plays an important role in the theoretical learning process for dental students. The combination of the atlas and electronic media based on portable mobile devices is beneficial for students' understanding of knowledge.

Background/Aims: Anti-phospholipase A2 receptor (PLA2R) autoantibody is the main biomarker of idiopathic membranous nephropathy (IMN). We aimed to find a new cutoff value of anti-PLA2R for patients with IMN and to explore the relevance between this antibody and baseline clinical parameters. Methods: A total of 670 subjects including 374 IMN cases and 296 non-IMN controls were included between January 2017 and January 2020. All clinical parameters were collected at the time of renal biopsy. The levels of anti-PLA2R were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit. The optimal cutoff value was calculated by a receiver operating characteristic curve and compared in diagnostic efficiency. Results: The optimal cutoff value of anti-PLA2R for IMN was 7.45 RU/mL with the highest Youden index, and the corresponding sensitivity, specificity, positive predictive value and negative predictive value were 80.75%, 97.97%, 98.05% and 80.11%, respectively. Anti-PLA2R levels in IMN patients demonstrated a significant positive correlation with serum creatinine and 24-hour urinary protein, while they showed a negative correlation with serum albumin and estimated glomerular filtration rate. Conclusions The recommended cutoff value of anti-PLA2R is 7.45 RU/mL using ELISA detection for distinguishing IMN from non-IMN nephropathy. The level of anti-PLA2R is related to baseline renal function in IMN. This new threshold can improve the diagnostic efficiency and facilitate early diagnosis of IMN.

Prostate cancer in patients with dwarfism is rarely reported. One case was reported in this article. The patient was admitted to the hospital due to the PSA elevation for more than 4 years. Due to the dwarf disease, the patient could not accommodate the transrectal ultrasound probe, and was highly suspected of prostate cancer.The prostate needle biopsy was not performed. Combined with the medical history, PSA level, preoperative MRI and PSMA-PET/CT examination, the patient was clinically diagnosed with localized prostate cancer, and radical surgical treatment was performed.

HYD-PEP06, an endostatin-modified polypeptide, has been shown to produce effective anti-colorectal carcinoma effects through inhibiting epithelial-mesenchymal transition (EMT). However, whether HYD-PEP06 has similar suppressive effect on hepatocellular carcinoma (HCC) remained unknown. In this study, HYD-PEP06 inhibited metastasis and EMT but not proliferation

Oral infectious diseases include caries, periodontal disease, halitosis, candidiasis albicans and so on. Over the past few decades, probiotics have mainly been studied in the field of the gastrointestinal tract. In recent years, probiotics have begun to be used in the prevention and treatment of various oral diseases and have become a new field in the research of oral disease prevention and control technology. This paper reviews the research progress of probiotics applied in the prevention and treatment of various oral infectious diseases. A review of the literature shows that probiotics can prevent and cure dental caries by inhibiting the growth of Streptococcus mutans and competing with them for nutrition and attachment sites. Probiotics not only inhibit periodontal pathogens and reduce the production of sulfide, they also regulate the body’s immune function to alleviate halitosis and periodontal inflammation. Probiotics can inhibit periodontal caries by inhibiting them. Probiotics can inhibit them mycelial growth of Candida albicans and interfere with its adherence, thus playing a role in the prevention and treatment of oral candidiasis. Current studies have shown that probiotics play an auxiliary role in the treatment of caries, periodontitis, halitosis and oral candidiasis. However, the mechanism of probiotics in the prevention and treatment of oral infectious diseases is still unclear, and the safety of probiotics remains to be further studied. In the future, oral probiotics should be studied with reference to intestinal probiotics to better work to prevent and treat oral diseases.