Objective To investigate the effect of spontaneous hypertension on the remodeling of cardiac and aortic tissues in rats, with special attention to the changes in the content of collagen fibers, elastic fibers and secreted Frizzled-related protein 2 （sFRP2） in cardiac and aortic tissues. Methods 28-week-old SHR rats （Spontaneously Hypertensive rats） and WKY （Wistar-Kyoto rats） of the same age were selected as experimental animals. Cardiac load was assessed by calculating the cardiac weight index. Collagen fibers and elastic fibers were isolated from the rat thoracic aorta by hot alkali method, and their content was determined by biochemical analysis. In addition, pathological evaluation of tissue sections of the left ventricle and thoracic aorta were performed by H&E staining, Sirius red staining, and lichen red staining. Western blotting was used to determine the expression level of sFRP2 protein in cardiac tissues. Results Compared with WKY rats, the heart weight index of SHR rats increased significantly （P<0.001）, and the results of biochemical analysis and staining of pathological sections showed that the content of collagen fibers in the aorta in the SHR group was higher than that in the WKY group, while the content of elastic fibers was lower, but the difference did not have statistical significance. The content of collagen fibers in the heart of the SHR group was significantly higher than that in the WKY group （P<0.01）. Western blotting showed that there was no significant difference in the expression level of sFRP2 protein in heart tissues between the two groups. Conclusion The remodeling of cardiac and aortic tissues in a rat model of spontaneous hypertension may involve complex molecular mechanisms, not just changes in the content of collagen fibers and elastic fibers. The detailed mechanism of the progression of spontaneous hypertension and target organs damage still need further investigation.

OBJECTIVE To investigate the effects of multiple doses of Shugan jieyu capsules on the pharmacokinetics of voriconazole， rivaroxaban and apixaban in rats. METHODS Male SD rats were randomly divided into voriconazole group （30 mg/kg）， rivaroxaban group （2 mg/kg）， apixaban group （0.5 mg/kg）， Shugan jieyu capsules+voriconazole group （145 mg/kg+30 mg/kg）， Shugan jieyu capsules+rivaroxaban group （145 mg/kg+2 mg/kg）， Shugan jieyu capsules+apixaban group （145 mg/kg+0.5 mg/kg）， with 6 rats in each group. After the rats in each group were consecutively administered solvent （0.5% sodium carboxymethyl cellulose solution） or Shugan jieyu capsules by intragastric gavage for 8 days， they were respectively given voriconazole， rivaroxaban and apixaban solution by intragastric gavage on the 8th day. Blood samples were then collected at different time points （in voriconazole group， rivaroxaban group and corresponding drug combination groups， blood was collected before administration and at 0.17， 0.34， 0.5， 0.75， 1， 1.5， 2， 3， 4， 5， 6， 8， 10 and 12 hours post-administration； in apixaban group and corresponding drug combination group， blood was collected before administration and at 0.08， 0.17， 0.25， 0.34， 0.5， 0.75， 1， 3， 5， 7， 10 and 12 hours post-administration）. Ultra-high performance liquid chromatography-tandem mass spectrometry method was employed to determine the mass concentrations of voriconazole， rivaroxaban and apixaban in rat plasma. The main pharmacokinetic parameters of these drugs were calculated using a non-compartmental model， and the comparisons were made between groups. RESULTS Compared with single drug group， after multiple administrations of Shugan jieyu capsules， AUC0－t， AUC0－∞ and cmax of voriconazole were significantly decreased， while CLz/F was significantly increased， and tmax was also significantly prolonged （P＜0.05）. For rivaroxaban and apixaban， their tmax values were both significantly prolonged （P＜0.05）. However， there were no statistically significant differences in the other pharmacokinetic parameters between the two groups （P＞0.05）. CONCLUSIONS The combination of Shugan jieyu capsules can decrease the exposure， increase the clearance， and delay the peak concentration of oral voriconazole. However， it does not affect the exposure levels of rivaroxaban and apixaban， but it does delay the time to reach peak concentration for both drugs.

Microalgae possess high photosynthetic efficiency, robust adaptability, and substantial biomass, serving as excellent biological resources for large-scale cultivation. Malic enzyme (ME), a ubiquitous metabolic enzyme in living organisms, catalyzes the decarboxylation of malate to produce pyruvate, CO₂, and NAD(P)H, playing a role in multiple metabolic pathways including energy metabolism, photosynthesis, respiration, and biosynthesis. In this study, we identified the Scenedesmus quadricauda malic enzyme gene (SqME) and its biological functions, aiming to provide excellent target genes for the genetic improvement of higher plants. Based on the RNA-seq data from S. quadricauda under the biofilm cultivation mode with high CO₂ and light energy transfer efficiency and small water use, a highly expressed gene (SqME) functionally annotated as ME was cloned. The physicochemical properties of the SqME-encoded protein were systematically analyzed by bioinformatics tools. The subcellular localization of SqME was determined via transient transformation in Nicotiana benthamiana leaves. The biological functions of SqME were identified via genetic transformation in Nicotiana tabacum, and the potential of SqME in the genetic improvement of higher plants was evaluated. The ORF of SqME was 1 770 bp, encoding 590 amino acid residues, and the encoded protein was located in chloroplasts. SqME was a NADP-ME, with the typical structural characteristics of ME. The ME activity in the transgenic N. tabacum plant was 1.8 folds of that in the wild-type control. Heterologous expression of SqME increased the content of chlorophyll a, chlorophyll b, and total chlorophyll by 20.9%, 26.9%, and 25.2%, respectively, compared with the control. The transgenic tobacco leaves showed an increase of 54.0% in the fluorescence parameter NPQ and a decrease of 30.1% in Fo compared with the control. Moreover, the biomass, total lipids, and soluble sugars in the transgenic tobacco leaves enhanced by 20.5%, 25.7%, and 9.5%, respectively. On the contrary, the starch and protein content in the transgenic tobacco leaves decreased by 22.4% and 12.2%, respectively. Collectively, the SqME-encoded protein exhibited a strong enzymatic activity. Heterologous expressing of SqME could significantly enhance photosynthetic protection, photosynthesis, and biomass accumulation in the host. Additionally, SqME can facilitate carbon metabolism remodeling in the host, driving more carbon flux towards lipid synthesis. Therefore, SqME can be applied in the genetic improvement of higher plants for enhancing photosynthetic carbon fixation and lipid accumulation. These findings provide scientific references for mining of functional genes from S. quadricauda and application of these genes in the genetic engineering of higher plants.
Nicotiana/genetics* ; Photosynthesis/physiology* ; Malate Dehydrogenase/biosynthesis* ; Plant Leaves/genetics* ; Scenedesmus/enzymology* ; Carbon Cycle/genetics* ; Lipid Metabolism/genetics* ; Plants, Genetically Modified/metabolism*

Objective To analyze the diagnostic process and clinical characteristics of autoimmune gastritis(AIG)in order to improve the awareness and diagnostic proficiency of this disease.Methods A retrospective cohort study was conducted on 114 patients diagnosed with AIG in Army Medical Center of PLA between January 2021 and June 2024.Comprehensive statistical analysis was performed on clinical data,including demographic characteristics(age,sex),clinical symptoms,comorbidities,diagnostic process,Helicobacter pylori(H.pylori)infection and treatment history,laboratory indicators[results of routine blood test,anemia-related indices,thyroid function,anti-parietal cell antibody(APCA),intrinsic factor antibody(IFA)],and gastrointestinal endoscopic findings(frequency and endoscopic features).Results Among the 114 patients,males accounted for 28.1%(32/114)and females for 71.9%(82/114),and they were at a mean age of 56.3±8.4 years.Predominant symptoms included epigastric/upper abdominal pain(47.4%,54/114)and postprandial fullness(43.0%,49/114),while 24.6%(28/114)reported acid reflux or heartburn.Diagnostic delay occurred in 76.4%(87/114)of patients,with a median delay duration of 11.5 months.Primary diagnostic clues were endoscopic reverse gradient atrophy(significantly more severe mucosal atrophy in the gastric corpus/fundus versus antrum;53.5%,61/114)and repeated H.pylori eradication failure(≥2 attempts;22.8%,26/114).Positivity rate of thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TgAb)was 56.9%(33/58)and 36.2%(21/58),respectively.APCA positive rate was 98.8%(81/82),IFA positive rate was 34.1%(28/82),and dual-antibody rate was 32.9%(27/82).Anemia was present in 25.7%(26/101)of the patients.Gastric neuroendocrine tumors(NET)were found in 12.2%(14/114),intraepithelial neoplasia in 5.3%(6/114),and gastric adenocarcinoma in 0.9%(1/114).Among colonoscopy-examined patients,tubular adenomas occurred in 25.0%(13/52)and colorectal malignancies in 3.4%(2/58).There were 18.4%(21/114)patients having gallbladder-related diseases,7.9%(9/114)having diabetes mellitus,and 1.8%(2/114)of subacute combined degeneration of the spinal cord.Conclusion AIG is frequently associated with diagnostic delay.The reverse pattern of atrophy on endoscopy serves as a critical diagnostic clue,necessitating enhanced recognition in endoscopists.Patients with recurrent H.pylori eradication failure(≥2 attempts)should be evaluated for AIG.

Objective To analyze the correlation between small patticle of lecithin,inflammatory factors,and immunoglobulins in prostatic fluid and chronic prostatitis(CP).Methods A total of 102 CP patients who were admitted to Beijing Puren Hospital from January 2022 to December 2023 were enrolled into CP group.According to the pathological classification of the National Institutes of Health in the United States,the patients were classified into type Ⅱ group(32 cases),type ⅢA group(39 cases),and type ⅢB group(31 cases).According to the severity of the disease,the patients were classified into mild group(33 cases),moderate group(43 cases),and severe group(26 cases).Meanwhile,34 healthy males who underwent physical examination were selected as controls.The levels of small patticle of lecithin(SPL),inflammatory factors,and immunoglobulins in prostate fluid were compared among groups.The relationship of these parameters with the pathological classification and severity of CP were analyzed.Results CP group had lower level of SPL and higher levels of tumor necrosis factor(TNF)-α,interleukin(IL)-6,IL-8,immunoglobulin(Ig)A,IgG,and IgM than control group(P<0.05).There was no significant difference in the SPL,IgA,IgG,or IgM among CP patients with different pathological types(P>0.05),but there were significant differences in the TNF-α,IL-6,and IL-8 levels(type Ⅱ group>type ⅢA group>type ⅢB group,P<0.05).There were significant differences in the SPL in CP patients with different severity levels(mild group>moderate group>severe group,P<0.05).So were the TNF-α,IL-6,IL-8,IgA,IgG,and IgM(severe group>moderate group>mild group,P<0.05).Spearman correlation analysis showed that SPL in the prostatic fluid was negatively correlated with the severity of CP(P<0.05);TNF-α,IL-6,and IL-8 were positively correlated with pathological classification and severity of CP(P<0.05);IgA,IgG,and IgM were positively correlated with the severity of CP(P<0.05).Conclusion SPL,TNF-α,IL-6,IL-8,IgA,IgG and IgM in prostatic fluid are closely related to the severity of CP.TNF-α,IL-6,and IL-8 in prostatic fluid are closely related to the pathological classification of CP.

Under the"Four Specials"conditions(special environments,special tasks,special equipment,and special personnel),complex tightly-coupled human-machine systems exhibit distinct characteristics such as human-in-the-loop,frequent human-machine interactions,and significant mutual influence between humans and machines.These features lead to prominent and typical human related safety issues.Through aggregating knowledge from literature review,accident case studies,and engineering practice,this paper elaborates on the characteristics of complex tightly-coupled human-machine systems,clarifies the definition of human related safety(including its research subjects,topics,and methods),and provides a systematic analysis framework on the causes of human related safety from a whole life-cycle perspective of system development.Furthermore,theoretical hypotheses are proposed for human related safety,along with its fundamental scientific research questions and methods.

Objective To investigate the rehabilitation efficacy of Beckman oral-motor training combined with auditory integration training(AIT)in children with language development delay.Methods A total of 118 children diagnosed with language development delay were enrolled in this study,and randomly assigned to auditory training group or combined training group,with 59 cases in each group.Children in the auditory training group received AIT,while those in the combined train-ing group underwent Beckman oral-motor training combined with AIT.The clinical efficacy,intellec-tual development,language ability,oral motor function,articulation ability,and serum neurotrophic factor levels of the two groups were observed and compared.Results After treatment,the overall ef-fective rate in the combined training group was 93.22％(55/59),which was significantly higher than 79.66％(47/59)in the auditory training group,with a statistically significant difference(P＜0.05).Following treatment,the scores of intellectual development,language ability,oral motor function,and articulation ability,as well as the serum levels of brain-derived neurotrophic factor(BDNF)and nerve growth factor(NGF)in both groups were elevated compared to the pre-treatment levels.Moreover,these parameters in the combined training group were superior to those in the audi-tory training group,and the differences were statistically significant(P＜0.05).Conclusion Beck-man oral-motor training combined with AIT can enhance the rehabilitation outcome in children with language development delay,improving their speech function,intellectual development,oral motor function,articulation ability,and serum neurotrophic factor levels.

Osteoporosis （OP） is a systemic metabolic bone disease characterized by bone microstructure degeneration and bone mass loss， which has a high prevalence and disability rate. Effective prevention and treatment of OP is a major difficulty in the medical community. The nature of OP is that multiple pathological factors lead to the imbalance of human bone homeostasis maintained by osteoblasts and osteoclasts. Ferroptosis is a non-apoptotic cell death pathway， and its fundamental cause is cell damage caused by iron accumulation and lipid peroxidation. Studies have shown that ferroptosis is involved in and affects the occurrence and development of OP， which leads to OP by mediating the imbalance of bone homeostasis. Ferroptosis is an adjustable form of programmed cell death. The intervention of ferroptosis can regulate the damage degree and death process of osteoblasts and osteoclasts， which is beneficial to maintain bone homeostasis， slow down the development process of OP， improve the clinical symptoms of patients， reduce the risk of disability， and improve their quality of life. However， there are few studies on ferroptosis in OP. Traditional Chinese medicine （TCM） is a medical treasure with unique characteristics and great application value in China. It has been widely used in China and has a long history. It has the multi-target and multi-pathway advantages in the treatment of OP， with high safety， few toxic and side effects， and low treatment cost， and has a significant effect in clinical application. The intervention of TCM in ferroptosis to regulate bone homeostasis may be a new direction for the prevention and treatment of OP in the future. This article summarized the regulatory mechanisms related to ferroptosis， discussed the role of ferroptosis in bone homeostasis， and reviewed the current status and progress of active ingredients in TCM compounds and monomers in the regulation of OP through ferroptosis， so as to provide a theoretical basis for the participation of TCM in the prevention and treatment of OP in the future.

Small interfering RNA (siRNA) has a promising future in the treatment of ocular diseases due to its high efficiency, specificity, and low toxicity in inhibiting the expression of target genes and proteins. However, due to the unique anatomical structure of the eye and various barriers, delivering nucleic acids to the retina remains a significant challenge. In this study, we rationally design PACD, an A-B-C type non-viral vector copolymer composed of a hydrophilic PEG block (A), a siRNA binding block (B) and a pH-responsive block (C). PACDs can self-assemble into nanosized polymeric micelles that compact siRNAs into polyplexes through simple mixing. By evaluating its pH-responsive activity, gene silencing efficiency in retinal cells, intraocular distribution, and anti-angiogenesis therapy in a mouse model of hypoxia-induced angiogenesis, we demonstrate the efficiency and safety of PACD in delivering siRNA in the retina. We are surprised to discover that, the PACD/siRNA polyplexes exhibit remarkable intracellular endosomal escape efficiency, excellent gene silencing, and inhibit retinal angiogenesis. Our study provides design guidance for developing efficient nonviral ocular nucleic acid delivery systems.

Background Welders' exposure to welding fumes with multiple metals leads to decreased pulmonary function. Previous studies have focused on single metal exposure, while giving little attention to the impact of metal mixtures. Objective To assess the association between metal levels in urine and blood of welders and pulmonary function indicators, and to identify key metals for occupational health risk assessment. Methods Questionnaire surveys, lung function tests, urine and blood sampling were conducted among welders and control workers in a shipyard in Shanghai. Inductively coupled plasma mass spectrometry (ICP-MS) was used to detect the concentrations of 12 metals such as vanadium, chromium, and manganese in urine and blood. Spearman correlation was applied to analyze the correlations between the metals in urine and blood. Multiple linear regression, weighted quantile sum (WQS) and Bayesian kernel machine regression (BKMR) were used to analyze the relationships between mixed metal exposure and pulmonary function parameters, such as forced vital capacity (FVC), forced vital capacity as a percentage of predicted value (FVC%), forced expiratory volume in the first second (FEV₁), forced expiratory volume in the first second as a percentage of predicted value (FEV₁%), and forced expiratory volume in the first second/forced vital capacity (FEV₁/FVC). Results This study enrolled 445 subjects, including 322 welders (72.36%) and 123 controls (27.64%). The mean age of the 445 participants was (37.64±8.80) years, and 87.19% participants were male. The welders had significantly higher levels of urinary cadmium (0.88 vs 0.58 μg·L⁻¹), blood chromium (5.86 vs 5.06 μg·L⁻¹), and blood manganese (24.24 vs 21.38 μg·L⁻¹) than the controls (P<0.05). The Spearman correlation coefficients between the metals in urine and blood ranged from −0.46 to 0.68. After adjustment for confounders, the multiple linear regression indicted that the urine molybdenum of the welders was negatively correlated with FVC and FEV₁. There were also negative correlations between the molybdenum in blood and FVC, FVC%, FEV₁, and FEV₁%, and between the copper in blood and FEV₁/FVC. The WQS model showed that FEV₁ and FVC decreased by 0.112 L and 0.353 L with each quartile increase of metal mixture concentrations in urine and blood among the welders respectively, and the leading contributors were copper, zinc, vanadium, and antimony. The BKMR model showed a negative overall effect of metal mixtures in urine and blood among the welders on FVC, FVC%, FEV₁, and FEV₁%, and the univariate exposure response-relationship between the molybdenum concentration in urine or blood and FVC, FVC%, FEV₁, or FEV₁% had an approximately linear decreasing trend. Meanwhile, there may be an interaction of cadmium with manganese, nickel, or vanadium, and an interaction of vanadium with iron, molybdenum, zinc, or copper, when different metals in urine among the welders interacted with FEV₁%. Conclusion Exposure to multiple metals in welders leads to a decline in lung function, with molybdenum, antimony, copper, and zinc as the leading contributors.