Osteoporosis （OP） is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast， traditional Chinese medicine has a long history and a rich species diversity. Furthermore， recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish， due to its favourable optical transparency and high homology with human genes， has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies， an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model， and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed， as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore， the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases， as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.

Objective To obtain the data of radiological diagnosis and treatment resource distribution at medical institutions of different levels and in various cities, understand the status of resource allocation, provide policy-making basis and suggestions for optimizing the allocation of radiological diagnosis and treatment resources within the province, and offer data and references for related research. Methods A basic situation questionnaire survey was conducted on radiological diagnosis and treatment institutions in Hunan Province. Data were reviewed, analyzed, and statistically processed using Excel software to understand the allocation situation of radiological diagnosis and treatment resources in Hunan Province. Results As of 2022, there were 3031 radiological diagnosis and treatment institutions, 19770 radiation workers, and 6617 pieces of radiological diagnostic and treatment equipment. There were 80 radiation treatment institutions, 49 nuclear medicine institutions, 178 interventional radiology institutions, and 3028 X-ray imaging diagnosis institutions. There were 1077 radiation workers in radiation treatment, 461 radiation workers in nuclear medicine, 3369 radiation workers in interventional radiology, and 14,863 radiation workers in X-ray imaging diagnosis. There were 135 pieces of radiation treatment equipment, 56 pieces of nuclear medicine equipment, 262 pieces of interventional radiology equipment, and 6164 pieces of X-ray imaging diagnosis equipment. Conclusion Primary and lower grade medical institutions in Hunan Province account for a relatively high proportion of the total number of medical institutions, whereas radiological diagnostic and treatment resources are predominantly concentrated in tertiary medical institutions, demonstrating a unbalanced allocation of radiological diagnosis and treatment resources in various cities. In terms of the overall allocation of radiological diagnosis and treatment resources, interventional radiology is superior to the national average, nuclear medicine and X-ray imaging diagnosis are comparable to the national averages, and radiation treatment is lower than the national average. The total GDP is not the decisive factor in determining the development of local medical levels. It is suggested that relevant authorities should improve the rationality of the planning for the allocation of radiological diagnosis and treatment resources, promote the allocation of radiological diagnosis and treatment resources to the grassroots and underdeveloped areas through various measures, and thus achieve the goal of balanced resource allocation.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To establish a method for determining hydrogen sulfide(H2S)in blood and apply it to practical cases.Methods A delute solution was achieved by adding 0.8 mL saturated borax solution into 0.2 mL blood sample was diluted with.1 mL acetonitrile solution containing 0.1％formic acid was then taken in a test tube,followed by adding 0.1 mL dilute solution and 0.1 mL thiozine aqueous solution(1％).After thorough mixing,the mixture was left to stand for 30 minutes.Subsequently,the sample was subjected to liquid chromatography-tandem mass spectrometry(LC-MS/MS)analysis after centrifugation and membrane filtration.Results The results showed that H2S exhibited good linearity within the concentration range of 10～2 000 ng/mL,with the R2 value of 0.998 5.The detection limit was 5 ng/mL,and the quantification limit was 10 ng/mL.In three cases of H2S poisoning,sulfur ions were detected in the blood of the deceased individuals,with concentrations ranging from 0.17 to 0.56 μg/mL.Conclusion For the first time,this study established a LC-MS/MS method for determining H2S in blood,which can meet the detection needs of H2S poisoning cases.

Respiratory diseases(e.g.,lung inflammation and pulmonary fibrosis)are a serious threat to human health.Mitochondria,organelles unique to eukaryotic cells,not only have important functions in energy production,biosynthesis,and the maintenance of intracellular homeostasis but also act as diverse signaling organelles involved in inflammation,proliferation,differentiation,cell repair,and other processes.The mitochondrial quality control system involves mitochondrial biogenesis,dynamics,and autophagy.Certain pathological mechanisms of respiratory diseases,such as oxidative stress and inflammation,are closely related to the dysregulation of mitochondrial quality control systems.This paper summarizes the progress of research into mitochondrial quality control dysregulation in respiratory diseases(chronic obstructive pulmonary disease,pulmonary fibrosis,acute lung injury,asthma,and bacterial pneumonia)to explore new ideas for the prevention and treatment of respiratory diseases.

Major depressive disorder(MDD)is a mental disease characterized by persistent depression,lack of interest and impaired cognitive function.Antidepressants currently availablein clinic are effective but accompanied by many adverse reactions,such as slow onset,cognitive impairment,sexual dysfunction.Therefore,novel antidepressant targets and therapeutic strategies with rapid onset of action,cognitive enhancement and low adverse effects have increasingly become a promising sphere of research.Studies have suggested that Sigma-1 receptor plays an important role in combating depression by regulating inflammatory response,excitation/inhibition balance and endoplasmic reticulum homeostasis.Moreover,Sigma-1 receptor agonists may have the advantages of rapid onset,enhanced cognition and low adverse reactions,which show good prospects for the development of new antidepressants.This article reviews the research progress related to Sigma 1 receptors in the regulatory mechanism and treatments for depression in the hopes of providing new insights into new antidepressants.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.

The significant clinical feature of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is the exposure of the necrotic jaw. Other clinical manifestations include jaw pain, swelling, abscess, and skin fistula, which seriously affect the patients' life, and there is no radical cure. Thus, new methods need to be found to prevent the occurrence of BRONJ. Here, a novel nanoparticle, tFNA-KLT, was successfully synthesized by us, in which the nanoparticle tetrahedral framework nucleic acid (tFNA) was used for carrying angiogenic peptide, KLT, and then further enhanced angiogenesis. TFNA-KLT possessed the same characteristics as tFNA, such as simple synthesis, stable structure, and good biocompatibility. Meanwhile, tFNA enhanced the stability of KLT and carried more KLT to interact with endothelial cells. First, it was confirmed that tFNA-KLT had the superior angiogenic ability to tFNA and KLT both in vitro and in vivo. Then we apply tFNA-KLT to the prevention of BRONJ. The results showed that tFNA-KLT can effectively prevent the occurrence of BRONJ by accelerating angiogenesis. In summary, the prepared novel nanoparticle, tFNA-KLT, was firstly synthesized by us. It was also firstly confirmed by us that tFNA-KLT significantly enhanced angiogenesis and can effectively prevent the occurrence of BRONJ by accelerating angiogenesis, thus providing a new avenue for the prevention of BRONJ and a new choice for therapeutic angiogenesis.
Angiogenic Proteins/therapeutic use* ; Bisphosphonate-Associated Osteonecrosis of the Jaw/prevention & control* ; Endothelial Cells ; Humans ; Nanoparticles ; Nucleic Acids/therapeutic use*

Objective:To investigate the intention of medical students to be vaccinated against COVID-19 and to analyze the influencing factors.Methods:A self-filled electronic questionnaire survey was conducted among medical students from a medical school in Shanghai randomly selected from June 21 to 29, 2021. The questionnaire contained items of basic information, intention for COVID-19 vaccination, awareness of COVID-19 prevention measures and awareness of COVID-19 vaccine. Logistic regression was used to analyze the influencing factors.Results:The average age of the 966 respondents was (20.4±2.9) years, and 63.6% (614/966) of them were female;23.7% (229/966) of them had family members or relatives who had participated in anti-pandemic work or volunteer service;90.6% (875/966) of the respondents expressed they were very willing or willing to be vaccinated against COVID-19. The majority of the respondents thought that “COVID-19 infection is very serious” (94.3%, 911/966), “good protection can effectively prevent COVID-19 infection” (92.4%, 893/966), and “they can fully implement all kinds of protection measures” (73.5%, 710/966). About half of the respondents (51.8%, 501/966) knew about the adverse reactions and contraindications of COVID-19 vaccine. The low protected capability (47.4%, 458/966), short duration of protection (50.6%, 489/966), and many side effects (48.7%, 470/966) were the major concerns about COVID-19 vaccine. Logistic regression analysis showed that people thought that “COVID-19 infection is very serious” ( OR=5.30, 95 %CI:2.60-10.81, P<0.001), thought that “good protection can effectively prevent COVID-19 infection” ( OR=2.46, 95 %CI:1.26-4.81, P=0.009), thought that “they can fully implement all kinds of protection measures” ( OR=2.55, 95 %CI:1.53-4.25, P<0.001) were more willing to receive COVID-19 vaccination. While those concerned about vaccine quality did the opposite ( OR=0.29, 95 %CI:0.13-0.65, P=0.003). Conclusions:Medical students have a high intention of vaccination against COVID-19. The vaccine-related knowledge quality should be emphasized in future publicity to further enhance the intention of COVID-19 vaccination.