ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction （SQDHD） on diabetic kidney disease （DKD）， with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group （n=10） and a modeling group （n=50）， with 43 mice successfully modeled. The successfully modeled mice were further allocated into model， low-， medium-， and high-dose （4.68， 9.36， and 18.72 g·kg^-1， respectively） SQDHD， and dapagliflozin （0.13 mg·kg^-1） groups. The drug treatment groups were administrated with corresponding agents by gavage， and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip， respectively. Serum creatinine （Scr） and blood urea nitrogen （BUN） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff （PAS） staining. The fluorescence intensity of reactive oxygen species （ROS） in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions （Fe²⁺） and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 （GPX4） and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter （xCT）， as well as the arachidonic acid metabolic pathway-related proteins， including ACSL4， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins， including solute carrier family 7 member 11 （SLC7A11） and GPX4， as well as arachidonic acid metabolism-related factors （ACSL4， LPCAT3， and ALOX15） in the renal tissue. ResultsCompared with the normal group， DKD model mice exhibited a decrease in body weight （P<0.01）， increases in levels of blood glucose （P<0.01）， 24-hour urinary protein， Scr， and BUN （P<0.01）， along with severe pathological changes， such as mesangial cell proliferation， basement membrane thickening， tubular atrophy， and interstitial inflammatory cell infiltration. In addition， the modeling elevated the levels of Fe²⁺， MDA， LPO， and ROS （P<0.01）， lowered the GPX4 and xCT levels （P<0.01）， raised the ACSL4， LPCAT3， and ALOX15 levels （P<0.01）， down-regulated the mRNA levels of GPX4 and SLC7A11 （P<0.01）， and up-regulated the mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01） in the renal tissue. Compared with the model group， low-， medium-， and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight （P<0.01）， decreases in levels of blood glucose （P<0.01）， 24-hour urinary protein， and Scr （P<0.01）， alleviated pathological changes in glomeruli and tubules， and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe²⁺， MDA， LPO， and ROS levels （P<0.01）. The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT （P<0.01）， decreased levels of ACSL4， LPCAT3， and ALOX15 （P<0.05， P<0.01）， and down-regulated mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01）. ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels， inhibiting lipid peroxidation， up-regulating GPX4 expression， and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.

ObjectiveTo investigate the therapeutic effects and mechanism of Shenqi Dihuang decoction （SQDHD） on diabetic kidney disease （DKD）， with a focus on its impact on arachidonic acid-related ferroptosis. MethodsSixty C57BL/6 mice were allocated into a normal group （n=10） and a modeling group （n=50）， with 43 mice successfully modeled. The successfully modeled mice were further allocated into model， low-， medium-， and high-dose （4.68， 9.36， and 18.72 g·kg^-1， respectively） SQDHD， and dapagliflozin （0.13 mg·kg^-1） groups. The drug treatment groups were administrated with corresponding agents by gavage， and the normal and model groups were administrated with equal volumes of normal saline by gavage. An electronic balance and a glucometer were used to monitor the body weight and fasting blood glucose level from the tail tip， respectively. Serum creatinine （Scr） and blood urea nitrogen （BUN） levels were measured by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in the renal tissue were assessed by hematoxylin-eosin staining， Masson staining， and periodic acid-Schiff （PAS） staining. The fluorescence intensity of reactive oxygen species （ROS） in frozen sections was observed by an inverted fluorescence microscope to evaluate the levels of ferrous ions （Fe²⁺） and lipid peroxidation in the renal tissue. Immunofluorescence staining of glutathione peroxidase 4 （GPX4） and acyl-CoA synthetase long-chain family member 4 （ACSL4） in the renal tissue was performed to detect their localization and expression. Western blot was employed to assess the expression levels of key ferroptosis proteins such as GPX4 and cystine/glutamate antiporter （xCT）， as well as the arachidonic acid metabolic pathway-related proteins， including ACSL4， lysophosphatidylcholine acyltransferase 3 （LPCAT3）， and arachidonate 15-lipoxygenase （ALOX15）. Real-time PCR was employed to measure the mRNA levels of key ferroptosis proteins， including solute carrier family 7 member 11 （SLC7A11） and GPX4， as well as arachidonic acid metabolism-related factors （ACSL4， LPCAT3， and ALOX15） in the renal tissue. ResultsCompared with the normal group， DKD model mice exhibited a decrease in body weight （P<0.01）， increases in levels of blood glucose （P<0.01）， 24-hour urinary protein， Scr， and BUN （P<0.01）， along with severe pathological changes， such as mesangial cell proliferation， basement membrane thickening， tubular atrophy， and interstitial inflammatory cell infiltration. In addition， the modeling elevated the levels of Fe²⁺， MDA， LPO， and ROS （P<0.01）， lowered the GPX4 and xCT levels （P<0.01）， raised the ACSL4， LPCAT3， and ALOX15 levels （P<0.01）， down-regulated the mRNA levels of GPX4 and SLC7A11 （P<0.01）， and up-regulated the mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01） in the renal tissue. Compared with the model group， low-， medium-， and high-dose SQDHD groups and the dapagliflozin group showed an increase in body weight （P<0.01）， decreases in levels of blood glucose （P<0.01）， 24-hour urinary protein， and Scr （P<0.01）， alleviated pathological changes in glomeruli and tubules， and reduced degree of glomerular and tubular fibrosis. The high-dose SQDHD group and the dapagliflozin group showed reductions in Fe²⁺， MDA， LPO， and ROS levels （P<0.01）. The medium- and high-dose SQDHD groups and the dapagliflozin group exhibited increased levels of GPX4 and xCT （P<0.01）， decreased levels of ACSL4， LPCAT3， and ALOX15 （P<0.05， P<0.01）， and down-regulated mRNA levels of ACSL4， LPCAT3， and ALOX15 （P<0.01）. ConclusionSQDHD ameliorates DKD by inhibiting ferroptosis potentially by reducing iron ion levels， inhibiting lipid peroxidation， up-regulating GPX4 expression， and down-regulating ACSL4 expression. This study provides new insights and a theoretical basis for the treatment of DKD with traditional Chinese medicine and identifies potential targets for developing novel therapeutics for DKD.

This research investigates the regulatory role of the transcription factor PU.1 in type 1 conventional dendritic cells (cDC1) and its therapeutic potential of modulating the nuclear factor kappaB (NF-κB) cells signaling pathway in non-small cell lung cancer (NSCLC). Utilizing single-cell transcriptome sequencing and comprehensive bioinformatics tools, including the CIBERSORT algorithm, we analyzed the immune cell landscape within NSCLC tissues. Our analysis revealed distinct NSCLC subtypes and delineated the developmental trajectories and functional distinctions of cDC1 cells. Key differentially expressed genes (DEGs) and pivotal functional modules within these cells were identified, highlighting PU.1 as a critical mediator underexpressed in NSCLC samples. Functionally, PU.1 demonstrated the induction of the NF-κB pathway, which led to inhibited tumor proliferation and enhanced activation of cDC1, thereby suggesting its role in tumor immune surveillance. In vivo models confirmed the suppressive effect of PU.1 on NSCLC progression, mediated through its influence on cDC1 functionality via the NF-κB pathway. These findings propose PU.1 as a promising target for NSCLC therapeutic strategies, emphasizing the importance of transcriptional regulators in the tumor microenvironment.

Objective To investigate the clonal rearrangement characteristics and clinical application value of IGH gene in B-cell non-Hodgkin's lymphoma(B-NHL).Methods Demographic and clinical data as well as IGH sequencing results of 55 patients with B-NHL who underwent next-generation sequencing(NGS)testing were collected,and IGH gene clonal rearrangement was detected.The characteristics of IGH gene clonal rearrangement,IGHV gene usage,and the clinical application value of NGS for IGH clonal rearrangement were analyzed.Results Among 55 patients with B-NHL and IGH clonal rearrangement,single dominant clones were mainly detected(85.45%,47/55);a few patients had two(12.73%,7/55)and three dominant clones(1.82%,1/55).In terms of preference for IGHV gene usage,IGHV3 gene had the highest frequency of access in B-NHL,followed by IGHV4.Among the IGHV subtypes,IGHV3-23 had the highest frequency in chronic lymphocytic leukemia/small lymphocytic lymphoma,and IGHV4-34 had the highest frequency in primary central nervous system diffuse large B-cell lymphoma and not otherwise specified diffuse large B-cell lymphoma.Conclusion A preference for IGHV gene usage in clonal rearr-angement of IGH genes is noted in B-NHL patients with different pathological types.Using NGS to detect IGHclonal rearrangement can identify subclones and clonal correlations,and assist in disease diagnosis.

Background An association between atmospheric fine particulate matter (PM_2.5) exposure and Parkinson's disease (PD) has been suggested by previous studies, but the results of current epidemiological studies are still inconclusive. Objective To systematically evaluate the relationship between exposure to ambient PM_2.5 and the risk of PD, as well as to explore potential influencing factors, aiming to provide scientific evidence for formulating early prevention strategies for PD. Methods Cochrane Library, PubMed, Web of Science, Medline, Embase, China National Know-ledge Infrastructure (CNKI), Wanfang Database, and VIP Chinese Science and Technology Journal Database were queried. The search terms included Parkinson's disease, particulate matter 2.5, and PM_2.5 in both Chinese and English. Cohort studies examining the association between atmospheric PM_2.5 exposure and the risk of PD were collected and searched from the inception of each database to June 26, 2023. The identified literature was screened, and the basic information of the included studies and their research subjects, outcome indicators, quantitative results of each study, as well as the information required by bias risk assessment were extracted. The Newcastle-Ottawa Scale was employed to assess the risk of literature bias. Meta-analysis, subgroup analysis, sensitivity analysis, and publication bias analysis were conducted in Stata 15.0 software. Results Twelve cohort studies were identified. A total of 17443136 participants with follow-up periods ranging from 3.5 to 22 years were included in the analysis. The meta-analysis, utilizing a random-effects model, revealed that PD risk was elevated by 6% after exposure to PM_2.5 [HR=1.06 (95%CI: 1.02, 1.11), P=0.006]. The subgroup analysis demonstrated that exposure to PM_2.5 increased PD risk by 6% in North America [HR=1.06 (95%CI: 1.00, 1.12), P=0.033] and by 17% in East Asia [HR=1.17 (95%CI: 1.02, 1.33), P=0.020]. However, the effect was not statistically significant in Europe. PD risk exhibited a 7% rise [HR=1.07 (95%CI: 1.02, 1.14), P=0.011] in individuals aged 60 years and older, which was different from that in individuals younger than 60 years. Exposure to various concentrations of PM_2.5 was observed to associate with an elevated risk of PD. The inclusion of adjustments for PD-related comorbidities did not alter the conclusion that ambient PM_2.5 exposure might elevate the risk of PD. The studies with a follow-up duration exceeding 5 years and reporting more than 1000 PD cases suggested a significant increase in the risk of PD due to ambient PM_2.5 exposure [HR=1.06 (95%CI: 1.01, 1.12), P=0.012; HR=1.06 (95%CI: 1.01, 1.11), P=0.027, respectively]. Conversely, no significant association was identified between ambient PM_2.5 exposure and the risk of PD within the cohorts with a follow-up duration of less than 5 years and reporting fewer than 1000 PD cases [HR=1.09 (95%CI: 0.95, 1.26), P=0.214; HR=1.12 (95%CI: 0.98, 1.02), P=0.092, respectively]. The sensitivity analysis showed that the results were stable. The publication bias analysis and the combined trim-and-fill method showed that the results were robust. Conclusion The risk of PD could be increased by ambient PM_2.5 exposure and influenced by age and area. The research results might be affected by the duration of follow-up and the quantity of PD cases reported.

Serine/arginine-rich splicing factor 7 (SRSF7), a known splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N⁶-methyladenosine (m⁶A) co-methylation network analysis across diverse cell lines, we find that the gene expression of SRSF7 is positively correlated with glioblastoma (GBM) cell-specific m⁶A methylation. We then indicate that SRSF7 is a novel m⁶A regulator, which specifically facilitates the m⁶A methylation near its binding sites on the mRNAs involved in cell proliferation and migration, through recruiting the methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of GBM cells largely dependent on the presence of the m⁶A methyltransferase. The two m⁶A sites on the mRNA for PDZ-binding kinase (PBK) are regulated by SRSF7 and partially mediate the effects of SRSF7 in GBM cells through recognition by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2). Together, our discovery reveals a novel role of SRSF7 in regulating m⁶A and validates the presence and functional importance of temporal- and spatial-specific regulation of m⁶A mediated by RNA-binding proteins (RBPs).
Humans ; Cell Line, Tumor ; Cell Proliferation ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Methyltransferases/metabolism* ; RNA Splicing Factors/metabolism* ; RNA, Messenger/genetics* ; RNA-Binding Proteins/metabolism* ; Serine-Arginine Splicing Factors/metabolism* ; RNA Methylation/genetics*

Collagen is a macromolecular protein constituting the extracellular matrix of animal connective tissue, which has been widely used and developed in fields of biomedicine, tissue engineering, food, and cosmetics. Due to its advantages such as abundant sources and good biocompatibility, low immunogenicity, and degradability, collagen can be used as a dressing or tissue engineering scaffold for wound repair. According to the source of materials, collagen can be divided into natural collagen and recombinant collagen. Natural collagen is mainly extracted directly from mammals and fish; recombinant collagen is obtained based on genetic engineering technology, and its sources include recombinant expression systems of microorganisms, animals, and plants. This paper summarizes the sources of collagen, and the roles, advantages, and disadvantages of different sources of collagen in wound repair, the particularity and superiority of collagen combined with three-dimensional printing technology in wound repair, the impact of market norms of China's collagen industry on the field of wound repair, and explains the precautions for the development of collagen-related products, aiming to provide new ideas for selecting a suitable source of collagen for wound repair.
Animals ; Collagen/metabolism* ; Wound Healing ; Tissue Engineering ; Tissue Scaffolds ; Cosmetics ; Mammals/metabolism*

Objective:To evaluate the clinical effect of high-intensity interval training and moderate continuous aerobic training on patients classified as low risk for exercise rehabilitation after a percutaneous coronary intervention (PCI).Methods:A total of 43 patients considered low-risk after a PCI were randomly divided into a high-intensity interval training group (HIIT group, 22 cases) and a moderate continuous aerobic training group (MCT group, 21 cases). The HIIT group received high-intensity, but aerobic interval training involving 8 rounds of 3 minutes of high-intensity exercise with 2-minute intervals at 80% of peak power over 40 minutes, 3 times a week. The MCT group trained continuously at 60% of peak power for the same duration. After 12 weeks both groups were given an ultrasound examination and a cardiopulmonary exercise test to assess their cardiac functioning and exercise endurance. The subjects′ life quality was evaluated and compared using some items from the SF-36 scale.Results:Before the training, no significant differences were observed in the average left ventricular ejection fraction, stroke volume, peak power, peak oxygen uptake, anaerobic threshold, physiological functioning, physical pain, general health or social functioning between the two groups. After the training significant improvement in all these indicators was observed in both groups, but compared with MCT group, the average left ventricular ejection fraction, stroke volume, peak power and peak oxygen uptake of the HIIT group were significantly better.Conclusions:High-intensity, aerobic interval training is superior to moderate but continuous aerobic training for improving the cardiac functioning and exercise endurance of patients suitable for exercise rehabilitation after a PCI. But there is no significant difference in their effect on the short-term quality of life.

Objective To explore the curative effect and safety of botulintum toxin A (BTX?A) on depressive disorder in patients with Parkinson′s disease (PD). Methods Forty?two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX?A group (administered with 100 U BTX?A injection on patients′eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self?rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self?rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow?up time point between the two groups were compared to evaluate the efficacy and safety of BTX?A in the treatment of PD patients with depression. Results The scores of HAMD, HAMA, SDS, SAS in the BTX?A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX?A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores:F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX?A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX?A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow?up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX?A group (P>0.05). Two of the 28 patients in the BTX?A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197). Conclusion BTX?A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.

Objective: To explore the curative effect and safety of botulintum toxin A (BTX-A) on depressive disorder in patients with Parkinson′s disease (PD). Methods: Forty-two cases of PD with depression prospectively recruited in the Second Hospital Affiliated to Soochow University from August 2016 to November 2018 were divided into two groups: 28 patients in BTX-A group (administered with 100 U BTX-A injection on patients′ eyebrow, forehead, bilateral lateral canthus and temporal region at 20 loci), 14 patients in sertraline (control) group (administered with 50-100 (55.36±14.47) mg/d sertraline). The scores of Hamilton Depression Rating Scale (HAMD), Self-rating Depression Scale (SDS), Hamilton Rating Scale for Anxiety (HAMA), Self-rating Anxiety Scale (SAS) after treatment for 2 weeks, 4 weeks, 8 weeks and 12 weeks were compared with the scores of each emotional rating scale for baseline respectively. Meanwhile, the differences in the scores of each emotional scale between the two treatment groups were compared. In addition, the remission rates of depression and anxiety (defined as HAMD, HAMA scores<7) at each follow-up time point between the two groups were compared to evaluate the efficacy and safety of BTX-A in the treatment of PD patients with depression. Results: The scores of HAMD, HAMA, SDS, SAS in the BTX-A group and the sertraline group reduced compared to baseline after treatment (at the 2nd, 4th, 8th, 12th weeks). The scores of HAMD and SDS in the BTX-A group (HAMD scores: F=12.930, P<0.01; SDS scores: F=5.022, P=0.001) and those in the sertraline group (HAMD scores: F=2.883, P=0.030; SDS scores: F=3.427, P=0.013) were significantly lower compared to baseline, but there was no statistically significant difference in the scores of HAMD and SDS between the two groups (P>0.05). HAMD score showed that the remission rate of depression in the BTX-A group (17.9% (5/28), 35.7% (10/28)) was higher than that of the sertraline group (2/14, 4/14) at the 2nd and 4th weeks. At the 8th and 12th weeks, the remission rate of depression in the sertraline group (7/14, 9/14) was higher than that of the BTX-A group (46.4% (13/28), 53.6% (15/28)). There was no statistically significant difference in remission rate of depression between the two groups at each follow-up time point (P>0.05). There was no statistically significant difference in HAMD scores between males and females in the BTX-A group (P>0.05). Two of the 28 patients in the BTX-A group had frown muscle stiffness, which lasted for two weeks and improved in one month. Two patients in the sertraline group had headache and dizziness, and two patients had dry mouth and nausea, which improved after two weeks. There was no statistically significant difference in the incidence of adverse reactions between the two groups (P=0.197). Conclusion BTX-A intraocular facial muscle injection can significantly improve the depressive symptoms of PD patients, and the effect lasts for a long time, with low incidence of side effects and high safety, which can be considered as a safe and effective new method for PD patients with depressive symptoms.