The renin-angiotensin-aldosterone system (RAAS) is crucial for regulating blood pressure and maintaining fluid balance, while clock genes are essential for sustaining biological rhythms and regulating metabolism. There exists a complex interplay between RAAS and clock genes that may significantly contribute to the development of various cardiovascular and metabolic diseases. Although current literature has identified correlations between these two systems, the specific mechanisms of their interaction remain unclear. Moreover, the interaction patterns under different physiological and pathological conditions need further investigation. This review summarizes the synergistic roles of the RAAS and clock genes in cardiovascular diseases, explores their molecular mechanisms and pathophysiological connections, discusses the application of chronotherapy, and highlights potential future research directions, aiming to provide novel insights for the prevention and treatment of related diseases.
Humans ; Renin-Angiotensin System/genetics* ; Cardiovascular Diseases/genetics* ; CLOCK Proteins/physiology* ; Animals

Pulmonary alveolar proteinosis(PAP)is a rare progressive respiratory dysfunction disease of the lung characterized by insidious onset and non-specific clinical manifestations,often leading to misdiagnosed and mistreated.Herein,we reported a case of PAP patient admitted to Jiading District Central Hospital with an atypical appearance of alveolar lavage fluid and whose condition improved significantly after treatment with subcutaneous injection of recombinant human granulocyte-macrophage colony stimulating factor(GM-CSF).Additionally,we have reviewed and summarized the relevant literature to enhance the understanding of the diagnosis and treatment of this disease.

Objectives:To analyze the correlation between cervical spine postures and different types of odontoid fractures when injured in different directions of violence using finite element method.Methods:Based on the experience of establishing the finite element model of the upper cervical vertebrae in the early stage,and verified as effective through literature published abroad and in vitro experiments,different positions of the cervical spine(neutral position,flexion position,extension position,lateral bending position,and rotation position)were preset on the established three-dimensional nonlinear finite element model of the normal occip-ital-atlantoaxial complex,and an acceleration of 8m/s2 was applied in each direction of violence[anterior,pos-terior,lateral,top(vertical downward)].The von Mises stress values in different regions of different types(An-derson and D'Alonzo type)of odontoid process fractures were calculated,and stress contour maps were ex-tracted.Results:When subjected to anterior violence,the maximum von Mises stress values were generated in an extension position,with stress concentration in the vertebral body of the axis(Type Ⅲ)(0.41MPa).When subjected to posterior violence,the maximum von Mises stress values were generated when the cervical vertebrae were in a flexion position,with stress concentration in the odontoid process base(Type Ⅱ)(0.52MPa)and the vertebral body of the axis(Type Ⅲ)(0.55MPa).When subjected to lateral violence,the maximum von Mises stress values were generated when the cervical vertebrae were in a flexion position,with stress concen-tration in the odontoid process base(Type Ⅱ)(0.51MPa)and the vertebral body of the axis(Type Ⅲ)(0.43MPa).When subjected to vertical downward violence,the stress values in each body position increased significantly,the stress at the tip of the odontoid process(Type Ⅰ)in the flexion position reached 0.99MPa,the stress at the base of the odontoid process(Type Ⅱ)in the lateral flexion position reached 1.16MPa,and the stress at the axis vertebral body(Type Ⅲ)in the rotational position was 0.85MPa.Conclusions:When the upper cervi-cal spine is in a flexion position and receives a vertically downward force,it is prone to odontoid process tip fractures(Type Ⅰ);When the upper cervical spine is in a flexion position and receives a posterior or lateral force,or when it is in a lateral bending position and receives a vertically downward force,it is prone to odontoid process base fractures(Type Ⅱ);When the upper cervical spine is in a flexion position and receives a posterior force,or when it is in a rotational position and receives a vertically downward force,it is prone to axis vertebral body fractures(Type Ⅲ).

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Probiotics play a crucial role in colon cancer treatment by metabolizing prebiotics to generate short-chain fatty acids (SCFAs). Colon cancer patients are frequently propositioned to supplement with probiotics to enhance the conversion and utilization of prebiotics. Nevertheless, the delivery and colonization of probiotics is hindered by the harsh conditions of gastrointestinal tract (GIT). Here, we devised a straightforward yet potent modified prebiotic-based "shield" (Gelatin-Inulin, GI), employing dietary inulin and natural polymer gelatin crosslinked via hydrogen bonding for enveloping Lactobacillus reuteri (Lr) to formulate synbiotic hydrogel capsules (Lr@Gl). The GI "shield" serves as a dynamic barrier, augmenting the resistance of Lr to gastric acid and facilitating its bioactivity and adherence in the GIT, synergizing with Lr to elicit an anti-tumor effect. Simultaneously, Lr@GI demonstrates anti-tumor effects by depleting glutathione to release reactive oxygen species, accompanied by the activation of NLRP3 (NOD-like receptor family pyrin domain containing 3), and the induction M1 macrophage polarization. Furthermore, Lr@GI can not only promote the recovery of intestinal barrier but also regulate intestinal flora, promoting the production of SCFAs and further exerting anti-tumor effect. Crucially, Lr@GI also potentiates the anti-tumor effect of 5-Fluorouracil. The construction and synergistic anti-tumor mechanism of synbiotic hydrogel capsules system provide valuable insights for gut microbial tumor therapy.

OBJECTIVE: To observe the clinical symptoms and MRI outcomes of patients with ruptured lumbar disc herniation(LDH) through a multicenter randomized controlled study, and to evaluate the clinical efficacy and safety of Yiqi Huoxue formula() in the treatment of this disease. METHODS: A total of 160 outpatients and inpatients with ruptured LDH admitted to 4 medical centers from January 2023 to June 2023 were selected and randomly divided into the Yiqi Huoxue formula group and the control group, with 80 patients in each group. In the Yiqi Huoxue formula group, there were 43 males and 37 females, with an age of (41.03±9.56) years and a disease duration of (10.45±25.37) days, and the patients were treated with Yiqi Huoxue formula. In the control group, there were 34 males and 46 females, with an age of (42.14±8.73) years and a disease duration of (11.31±21.14) days;during the acute phase, patients in this group could take celecoxib capsules orally, and methylcobalamin orally at the same time. The Japanese Orthopaedic Association (JOA) score, Oswestry disability index (ODI), changes in the volume of herniated disc tissue on MRI, herniation rate, and absorption rate were recorded at the time of enrollment and during follow-ups at the 3rd, 6th, and 12th month after treatment. RESULTS: A total of 156 patients completed the clinical follow-up, and 4 patients withdrew midway. The clinical symptoms of all patients who completed the study were relieved to varying degrees, and reabsorption of herniated disc tissue was observed in all patients in the Yiqi Huoxue formula group after treatment. For the JOA score:in the Yiqi Huoxue formula group, it was (10.73±2.76) points before treatment and (24.65±2.19) points at the 12th month after treatment;in the control group, it was (11.01±1.20) points before treatment and (17.07±3.26) points at the 12th month after treatment. For the ODI score:in the Yiqi Huoxue formula group, it was (26.21±3.55) points before treatment and (5.65±2.19) points at the 12th month after treatment;in the control group, it was (27.92±2.51) points before treatment and (9.09±2.15) points at the 12th month after treatment. At the 12th month after treatment, the JOA and ODI scores of both groups were better than those before treatment, and the scores of the Yiqi Huoxue formula group were better than those of the control group, with statistically significant differences (P<0.05). In terms of the herniated disc volume and herniation rate on MRI, the Yiqi Huoxue formula group was superior to the control group, with statistically significant differences(P<0.05). Reabsorption occurred in 56.96%(45/79) of patients in the Yiqi Huoxue formula group, which was significantly higher than the 37.66%(29/77) in the control group. CONCLUSION After treatment with Yiqi Huoxue formula, patients with ruptured LDH show significant improvement in clinical symptoms and a marked reduction in the volume of herniated discs. During the follow-up period, no obvious adverse drug reactions are observed in patients, and no recurrence of symptoms is found at the last follow-up, indicating that the formula has safe and reliable efficacy.
Humans ; Male ; Female ; Intervertebral Disc Displacement/drug therapy* ; Adult ; Drugs, Chinese Herbal/adverse effects* ; Middle Aged ; Lumbar Vertebrae

OBJECTIVE: To explore the safety and efficacy of high-dose etoposide (VP-16) combined with recombinant human granulocyte colony-stimulating factor (rhG-CSF) as salvage mobilization for peripheral blood stem cells (PBSC) in newly diagnosed multiple myeloma (NDMM) patients. METHODS: From April 2021 to May 2023, eight NDMM patients who had failed to yield sufficient PBSC during initial mobilization with high-dose cyclophosphamide (CTX) combined with rhG-CSF underwent salvage mobilization with 1.2 g/m2 etoposide combined with rhG-CSF 10 μg/(kg·d). The effects and adverse reactions of initial mobilization and salvage mobilization were analyzed. RESULTS: For salvage mobilization and initial mobilization, the numbers of PBSC collections were 16 and 18, respectively. The mean value of total collected CD34⁺ cells were (11.90±5.75)×10⁶/kg and (1.67±0.75)×10⁶/kg (P =0.0010) in salvage mobilization group and initial mobilization group, respectively. The proportion of patients with a total collection of CD34⁺ cell count≥2×10⁶/kg were 100% and 37.5% (P =0.0625), and the proportion of patients with a total collection of CD34⁺ cell count≥5×10⁶/kg were 87.5% and 0% (P =0.0156) in salvage mobilization group and initial mobilization group, respectively. For five patients who underwent high-dose CTX initial mobilization but had a total CD34⁺ cell count < 2×10⁶/kg, successful collection was achieved through salvage mobilization with high-dose VP-16. Salvage mobilization with high-dose VP-16 was scheduled 2-3 weeks after failure of CTX mobilization. Adverse reactions of high-dose VP-16 mobilization did not increase compared to the initial mobilization with high-dose CTX. CONCLUSION As a salvage mobilization regimen, VP-16 1.2 g/m² combined with rhG-CSF is safe and highly effective in NDMM patients who failed to initial mobilization with high-dose CTX combined with rhG-CSF.
Humans ; Multiple Myeloma/therapy* ; Etoposide/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor ; Salvage Therapy ; Peripheral Blood Stem Cells ; Male ; Middle Aged ; Female ; Peripheral Blood Stem Cell Transplantation

An integrated extraction-purification process was established in this work for efficient phycocyanin production from dried Spirulina platensispowder.Initially,phycocyanin was extracted from algal biomass using a combined swelling-enzymatic lysis strategy.Single-factor experiments were carried out to systematically evaluate the effects of critical parameters,including system pH,enzymatic hydrolysis duration,and temperature,on phycocyanin extraction yield.Subsequently,a three-factor,three-level Box-Behnken response surface methodology design was employed to optimize the extraction process,with phycocyanin concentration and purity in the extract serving as response variables.A predictive regression model identified optimal conditions as follows:pH 6.4,hydrolysis time 3.2 h,and temperature 35.4℃.Experimental validation under these conditions yielded a phycocyanin recovery of 26.6%.Following extraction,purification was achieved via a polyethylene glycol-phosphate aqueous two-phase extraction system,which elevated the final purity to 4.21.Results demonstrated that the swelling-enzymatic lysis approach effectively disrupted algal cellular structures,significantly enhancing phycocyanin release efficiency.Concurrently,the aqueous two-phase system enabled selective partitioning and enrichment of the target protein under mild conditions.The integrated process exhibited high extraction efficiency,gentle purification,and robust operability,rendering it suitable for the scalable production of natural phycocyanin.This work provided both methodological foundations and technical support for advancing phycocyanin applications in natural pigments,biomedicine,and analytical detection.

Pulmonary alveolar proteinosis(PAP)is a rare progressive respiratory dysfunction disease of the lung characterized by insidious onset and non-specific clinical manifestations,often leading to misdiagnosed and mistreated.Herein,we reported a case of PAP patient admitted to Jiading District Central Hospital with an atypical appearance of alveolar lavage fluid and whose condition improved significantly after treatment with subcutaneous injection of recombinant human granulocyte-macrophage colony stimulating factor(GM-CSF).Additionally,we have reviewed and summarized the relevant literature to enhance the understanding of the diagnosis and treatment of this disease.

Objectives:To analyze the correlation between cervical spine postures and different types of odontoid fractures when injured in different directions of violence using finite element method.Methods:Based on the experience of establishing the finite element model of the upper cervical vertebrae in the early stage,and verified as effective through literature published abroad and in vitro experiments,different positions of the cervical spine(neutral position,flexion position,extension position,lateral bending position,and rotation position)were preset on the established three-dimensional nonlinear finite element model of the normal occip-ital-atlantoaxial complex,and an acceleration of 8m/s2 was applied in each direction of violence[anterior,pos-terior,lateral,top(vertical downward)].The von Mises stress values in different regions of different types(An-derson and D'Alonzo type)of odontoid process fractures were calculated,and stress contour maps were ex-tracted.Results:When subjected to anterior violence,the maximum von Mises stress values were generated in an extension position,with stress concentration in the vertebral body of the axis(Type Ⅲ)(0.41MPa).When subjected to posterior violence,the maximum von Mises stress values were generated when the cervical vertebrae were in a flexion position,with stress concentration in the odontoid process base(Type Ⅱ)(0.52MPa)and the vertebral body of the axis(Type Ⅲ)(0.55MPa).When subjected to lateral violence,the maximum von Mises stress values were generated when the cervical vertebrae were in a flexion position,with stress concen-tration in the odontoid process base(Type Ⅱ)(0.51MPa)and the vertebral body of the axis(Type Ⅲ)(0.43MPa).When subjected to vertical downward violence,the stress values in each body position increased significantly,the stress at the tip of the odontoid process(Type Ⅰ)in the flexion position reached 0.99MPa,the stress at the base of the odontoid process(Type Ⅱ)in the lateral flexion position reached 1.16MPa,and the stress at the axis vertebral body(Type Ⅲ)in the rotational position was 0.85MPa.Conclusions:When the upper cervi-cal spine is in a flexion position and receives a vertically downward force,it is prone to odontoid process tip fractures(Type Ⅰ);When the upper cervical spine is in a flexion position and receives a posterior or lateral force,or when it is in a lateral bending position and receives a vertically downward force,it is prone to odontoid process base fractures(Type Ⅱ);When the upper cervical spine is in a flexion position and receives a posterior force,or when it is in a rotational position and receives a vertically downward force,it is prone to axis vertebral body fractures(Type Ⅲ).