ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

Tendon-bone healing is a complex biological process. Multiple signaling pathways are involved in tendon-bone healing， including transforming growth factor-β signaling pathway， bone morphogenetic protein signaling pathway， Wnt signaling pathway， fibroblast growth factor signaling pathway and nuclear transcription factor-κB signaling pathway. This paper summarizes the research status of traditional Chinese medicine regulating related signaling pathways to promote tendon-bone healing. It is found that a variety of traditional Chinese medicine monomers or herbal extracts （such as baicalein， icariin， total flavonoids of Drynaria fortunei， parthenolide， total saponins of Panax notoginseng， etc.） and traditional Chinese medicine compounds （such as Taohong siwu decoction， Liuwei dihuang pill， Xujin jiegu liquid， etc.） can promote bone formation， anti-inflammatory， anti-oxidation， by regulating the above signaling pathways， thereby effectively promoting tendon-bone healing.

Medical and pharmaceutical research laboratories encompass a wide range of study areas.They utilize diverse materials ranging from animals and microorganisms to nanoparticles and other substances.However,as laboratory waste increases,more biosafety risks are created.In this context,we outlined the safety risks associated with gene amplification,gene recombination,research involving pathogenic microorganisms,nanotechnology,animal experiments,genetically modified animals,and experimental waste.Additionally,we here in propose preventive measures to mitigate laboratory biosafety risks.These measures primarily involve the development of strict legal frameworks,improvement of hardware infrastructure,strengthening of safety awareness,and enhancement of education and training programs.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Objective:To prepare the chitin/hyaluronic acid/collagen hydrogel loaded with mouse adipose-derived stem cells and to explore its effects on wound healing of full-thickness skin defects in rats.Methods:The research was an experimental research. Chitin nanofibers were prepared by acid hydrolysis and alkaline extraction method, and then mixed with hyaluronic acid and collagen to prepare chitin/hyaluronic acid/collagen hydrogels (hereinafter referred to as hydrogels). Besides, the hydrogels loaded with mouse adipose-derived stem cells were prepared. Thirty male 12-week-old guinea pigs were divided into negative control group, positive control group, and hydrogel group according to the random number table, with 10 guinea pigs in each group. Ethanol, 4-aminobenzoic acid ethyl ester, or the aforementioned prepared hydrogels without cells were topically applied on both sides of back of guinea pigs respectively for induced contact and stimulated contact, and skin edema and erythema formation were observed at 24 and 48 h after stimulated contact. Adipose-derived stem cells from mice were divided into normal control group cultured routinely and hydrogel group cultured with the aforementioned prepared hydrogels without cells. After 3 d of culture, protein expressions of platelet-derived growth factor-D (PDGF-D), insulin-like growth factor-Ⅰ (IGF-Ⅰ), and transforming growth factor β 1 (TGF-β 1) were detected by Western blotting ( n=3). Eight male 8-week-old Sprague-Dawley rats were taken and a circular full-thickness skin defect wound was created on each side of the back. The wounds were divided into blank control group without any treatment and hydrogel group with the aforementioned prepared hydrogels loaded with adipose-derived stem cells applied. Wound healing was observed at 0 (immediately), 2, 4, 8, and 10 d after injury, and the wound healing rate was calculated at 2, 4, 8, and 10 d after injury. Wound tissue samples at 10 d after injury were collected, the new tissue formation was observed by hematoxylin-eosin staining; the concentrations of interleukin-1α (IL-1α), IL-6, IL-4, and IL-10 were detected by enzyme-linked immunosorbent assay method; the expressions of CD16 and CD206 positive cells were observed by immunohistochemical staining and the percentages of positive cells were calculated. The sample numbers in animal experiment were all 8. Results:At 24 h after stimulated contact, no skin edema was observed in the three groups of guinea pigs, and only mild skin erythema was observed in 7 guinea pigs in positive control group. At 48 h after stimulated contact, skin erythema was observed in 8 guinea pigs and skin edema was observed in 4 guinea pigs in positive control group, while no obvious skin erythema or edema was observed in guinea pigs in the other two groups. After 3 d of culture, the protein expression levels of PDGF-D, IGF-I, and TGF-β 1 in adipose-derived stem cells in hydrogel group were significantly higher than those in normal control group (with t values of 12.91, 11.83, and 7.92, respectively, P<0.05). From 0 to 10 d after injury, the wound areas in both groups gradually decreased, and the wounds in hydrogel group were almost completely healed at 10 d after injury. At 4, 8, and 10 d after injury, the wound healing rates in hydrogel group were (38±4)%, (54±5)%, and (69±6)%, respectively, which were significantly higher than (21±6)%, (29±7)%, and (31±7)% in blank control group (with t values of 3.82, 3.97, and 4.05, respectively, Pvalues all <0.05). At 10 d after injury, compared with those in blank control group, the epidermis in wound in hydrogel group was more intact, and there were increases in hair follicles, blood vessels, and other skin appendages. At 10 d after injury, the concentrations of IL-1α and IL-6 in wound tissue in hydrogel group were significantly lower than those in blank control group (with tvalues of 8.21 and 7.99, respectively, P<0.05), while the concentrations of IL-4 and IL-10 were significantly higher than those in blank control group (with tvalues of 6.57 and 9.03, respectively, P<0.05). The percentage of CD16 positive cells in wound tissue in hydrogel group was significantly lower than that in blank control group ( t=8.02, P<0.05), while the percentage of CD206 positive cells was significantly higher than that in blank control group ( t=7.21, P<0.05). Conclusions:The hydrogel loaded with mouse adipose-derived stem cells is non-allergenic, can promote the secretion of growth factors in adipose-derived stem cells, promote the polarization of macrophages to M2 phenotype in wound tissue in rats with full-thickness skin defects, and alleviate inflammatory reaction, thereby promoting wound healing.

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. The focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

Background::Genetic variants of dopaminergic transcription factor-encoding genes are suggested to be Parkinson’s disease (PD) risk factors; however, no comprehensive analyses of these genes in patients with PD have been undertaken. Therefore, we aimed to genetically analyze 16 dopaminergic transcription factor genes in Chinese patients with PD.Methods::Whole-exome sequencing (WES) was performed using a Chinese cohort comprising 1917 unrelated patients with familial or sporadic early-onset PD and 1652 controls. Additionally, whole-genome sequencing (WGS) was performed using another Chinese cohort comprising 1962 unrelated patients with sporadic late-onset PD and 1279 controls.Results::We detected 308 rare and 208 rare protein-altering variants in the WES and WGS cohorts, respectively. Gene-based association analyses of rare variants suggested that MSX1 is enriched in sporadic late-onset PD. However, the significance did not pass the Bonferroni correction. Meanwhile, 72 and 1730 common variants were found in the WES and WGS cohorts, respectively. Unfortunately, single-variant logistic association analyses did not identify significant associations between common variants and PD. Conclusions::Variants of 16 typical dopaminergic transcription factors might not be major genetic risk factors for PD in Chinese patients. However, we highlight the complexity of PD and the need for extensive research elucidating its etiology.

Objective    To investigate effectiveness and safety of transcatheter aortic valve replacement in the treatment of aortic regurgitation. Methods     PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data and VIP were searched from inception to August 2021. According to the criteria of inclusion and exclusion, two reviewers independently screened the literature, extracted the data and evaluated the quality of the included studies. Then, Stata 16.0 software was used for meta-analysis. Subgroup meta-analysis of valve type used and study type was performed. Results    Twenty-five studies (12 cohort studies and 13 single-arm studies) were included with 4 370 patients. Meta-analysis results showed that an incidence of device success was 87% (95%CI 0.81-0.92). The success rate of the new generation valve subgroup was 93% (95%CI 0.89-0.96), and the early generation valve subgroup was 66% (95%CI 0.56-0.75). In addition, the 30-day all-cause mortality was 7% (95%CI 0.05-0.10), the 30-day cardiac mortality was 4% (95%CI 0.01-0.07), the incidence of pacemaker implantation was 10% (95%CI 0.08-0.13), and the incidence of conversion to thoraco-tomy was 2% (95%CI 0.01-0.04). The incidence of moderate or higher paravalvular aortic regurgitation was 6% (95%CI  0.03-0.09). Conclusion     Transcatheter aortic valve replacement for aortic regurgitation is safe and yields good results, but some limitations can not be overcome. Therefore, multicenter randomized controlled trials are needed to confirm our results.

Objective The incidence of coronary microvascular disease(CMVD)is increasing annually.According to traditional Chinese medicine(TCM),CMVD belongs to the category of"collaterals",and qi deficiency and blood stasis are the main syndrome type of CMVD.Notably however,no studies have reported on the use of animal models of CMVD with qi deficiency and blood stasis.The current study therefore aimed to establish and evaluate a rat model of CMVD with qi deficiency and blood stasis syndrome.Methods Forty-five male SD rats were divided randomly into sham group,CMVD group,and CMVD + QXXY group(n = 15 rats per group).Rats in the CMVD + QXXY group were randomly deprived of sleep for 14～16 h/day for 6 weeks,and the model of qi deficiency syndrome was established.Animals in the sham group and the CMVD group were fed normally for 6 weeks.After 6 weeks,rats in the CMVD and CMVD + QXXY groups were anesthetized,their chests were opened,and embolic microspheres(40～120 μm)were injected into the left ventricle.Rats in the sham group underwent thoracotomy without injection of embolic microspheres.On day 7 after operation,relevant detection indicators were measured in each group.Results Compared with the sham group,the CMVD group showed a significant decrease in left ventricular ejection fraction and left ventricular shortening rate,while the activities of creatine kinase MB isoenzyme(CK-MB)and lactate dehydrogenase(LDH)were significantly increased.Heart function,hemorheology,myocardial enzyme index,and the degree of myocardial cell damage differed significantly between the CMVD + QXXY group compared with the sham group.Conclusions A rat model of CMVD + qi deficiency + blood stasis syndrome can be successfully established by sleep deprivation combined with intraventricular injection of embolic microspheres.This model will be suitable for the study of the pathogenesis of CMVD and the mechanisms of TCM.

Objective:To analyze the surveillance data of Kashin-Beck disease (KBD) in Shandong Province, master the changes of KBD, and provide scientific basis for formulating prevention and control strategies of KBD and adjustment of the prevention and control focus of KBD.Methods:According to the requirements of the "National KBD Monitoring Plan" and the "Shandong KBD Monitoring Plan", from 2016 to 2020, the disease monitoring was carried out in the villages of KBD areas in Shandong Province, including the number of clinical positive cases, the number of X-ray positive cases, and the number of metaphyseal positive cases. The detection rate was calculated, and the dynamic changes of the disease was analyzed macroscopically.Results:From 2016 to 2020, a total of 1 816 children aged 7 - 12 years were clinically examined in Shandong Province, and no child with KBD was found. A total of 1 224 children were examined by X-ray, among which 1 positive patient was found in 2016 and 2017, respectively, both of whom were metaphyseal changes, with a total detection rate of 0.16%. There were 367 adult patients with KBD in Shandong Province, including 304 patients with grade Ⅰ, 47 patients with grade Ⅱ and 16 patients with grade Ⅲ. All villages in the KBD areas in Shandong Province had reached the elimination standard, with the elimination rate of 100%.Conclusion:No clinical case of KBD is detected in children aged 7 - 12 years in Shandong Province from 2016 to 2020, which has reached the elimination standard and is in a continuous elimination state.