ObjectiveTo explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments. MethodsThe drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules， and constipation-related targets were collected from disease databases. A protein-protein interaction （PPI） network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets， which was followed by gene ontology （GO） function and Kyoto encyclopedia of genes and genomes （KEGG） pathway enrichment analyses. A "bioactive component-target-pathway" network was constructed， and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network. Molecular docking was employed to predict the binding affinity of core components to key targets. A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation. ResultsThe PPI network revealed six key constipation-related targets： protein kinase B （Akt1）， B-cell lymphoma-2 （Bcl-2）， glycogen synthase kinase-3β （GSK-3β）， cyclooxygenase-2 （PTGS2）， estrogen receptor 1 （ESR1）， and epidermal growth factor receptor （EGFR）. The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase （PI3K）/Akt signaling pathway was the most enriched. The topological parameter analysis of the "bioactive component-target-pathway" network screened out the top 10 core components： auranetin， isosinensetin， naringin， diosmetin， quercetin， apigenin， luteolin， hesperidin， isorhapontigenin， and chrysophanol. Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets. Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules， the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propulsion rate of mice were improved. After treatment with Shouhui Tongbian capsules， the colonic mucosal injury and glandular arrangement were alleviated， and the muscle layer thickness was increased. Western blot results showed that Shouhui Tongbian capsules recovered the expression of apoptosis-related molecules mediated by the PI3K/Akt pathway in the colonic tissue of constipated mice. Terminal-deoxynucleotidyl transferase-mediated nick end labeling （TUNEL） results showed that the cell apoptosis rate of the colon significantly reduced after intervention with Shouhui Tongbian capsules. ConclusionThe results of network pharmacology and animal experiments confirmed that Shouhui Tongbian capsules can treat constipation through multiple targets and pathways. The capsules can effectively intervene in loperamide-induced constipation in mice by regulating the constipation indicators and reducing cell apoptosis in the colon tissue via activating the PI3K/Akt signaling pathway.

The Golgi apparatus (GA) is a key membranous organelle in eukaryotic cells, acting as a central component of the endomembrane system. It plays an irreplaceable role in the processing, sorting, trafficking, and modification of proteins and lipids. Under normal conditions, the GA cooperates with other organelles, including the endoplasmic reticulum (ER), lysosomes, mitochondria, and others, to achieve the precise processing and targeted transport of nearly one-third of intracellular proteins, thereby ensuring normal cellular physiological functions and adaptability to environmental changes. This function relies on Golgi protein quality control (PQC) mechanisms, which recognize and handle misfolded or aberrantly modified proteins by retrograde transport to the ER, proteasomal degradation, or lysosomal clearance, thus preventing the accumulation of toxic proteins. In addition, Golgi-specific autophagy (Golgiphagy), as a selective autophagy mechanism, is also crucial for removing damaged or excess Golgi components and maintaining its structural and functional homeostasis. Under pathological conditions such as oxidative stress and infection, the Golgi apparatus suffers damage and stress, and its homeostatic regulatory network may be disrupted, leading to the accumulation of misfolded proteins, membrane disorganization, and trafficking dysfunction. When the capacity and function of the Golgi fail to meet cellular demands, cells activate a series of adaptive signaling pathways to alleviate Golgi stress and enhance Golgi function. This process reflects the dynamic regulation of Golgi capacity to meet physiological needs. To date, 7 signaling pathways related to the Golgi stress response have been identified in mammalian cells. Although these pathways have different mechanisms, they all help restore Golgi homeostasis and function and are vital for maintaining overall cellular homeostasis. It is noteworthy that the regulation of Golgi homeostasis is closely related to multiple programmed cell death pathways, including apoptosis, ferroptosis, and pyroptosis. Once Golgi function is disrupted, these signaling pathways may induce cell death, ultimately participating in the occurrence and progression of diseases. Studies have shown that Golgi homeostatic imbalance plays an important pathological role in various major diseases. For example, in Alzheimer’s disease (AD) and Parkinson’s disease (PD), Golgi fragmentation and dysfunction aggravate the abnormal processing of amyloid β-protein (Aβ) and Tau protein, promoting neuronal loss and advancing neurodegenerative processes. In cancer, Golgi homeostatic imbalance is closely associated with increased genomic instability, enhanced tumor cell proliferation, migration, invasion, and increased resistance to cell death, which are important factors in tumor initiation and progression. In infectious diseases, pathogens such as viruses and bacteria hijack the Golgi trafficking system to promote their replication while inducing host defensive cell death responses. This process is also a key mechanism in host-pathogen interactions. This review focuses on the role of the Golgi apparatus in cell death and major diseases, systematically summarizing the Golgi stress response, regulatory mechanisms, and the role of Golgi-specific autophagy in maintaining homeostasis. It emphasizes the signaling regulatory role of the Golgi apparatus in apoptosis, ferroptosis, and pyroptosis. By integrating the latest research progress, it further clarifies the pathological significance of Golgi homeostatic disruption in neurodegenerative diseases, cancer, and infectious diseases, and reveals its potential mechanisms in cellular signal regulation.

Objective To investigate whether Liuwei Dihuang Pills enhances the antigen cross-presenting ability of dendritic cell(DC)by increasing gap junctional intercellular communication(GJIC),and to explore the mechanisms involved.Methods Western Blot and immunofluorescence were used to observe the effects of Liuwei Dihuang Pills-containing serum on the expression and membrane localisation of gap junction protein connexin43(Cx43)in mouse melanoma cells(B16);Calcein-AM/DiI fluorescence tracer assay was used to observe the effects of Liuwei Dihuang Pills-containing serum on the function of GJIC in B16 cells;flow cytometry was used to observe the role of GJIC in the enhancement of DC antigen presenting ability by Liuwei Dihuang Pills-containing serum;and propidium iodide(PI)/Hoechst staining assay was used to observe the immunocidal effect of CD8+ T-lymphocytes.Results Western Blot and immunofluorescence experiments showed that Liuwei Dihuang Pills-containing serum led to the up-regulation of Cx43 expression;fluorescence tracer experiments proved that the GJIC function of B16 cells was significantly enhanced by Liuwei Dihuang Pills-containing serum;flow cytometry analyses showed that the DC antigen-presenting ability was enhanced by Liuwei Dihuang Pills-containing serum;and the results of PI/Hoechst staining showed that the immuno-killing effect of CD8+T-cells was more significant after the intervention of Liuwei Dihuang Pills-containing serum in B16-OVA.Conclusion Liuwei Dihuang Pills improve the GJIC function by up-regulating the Cx43 expression of melanoma cells,and then enhance the cross-presenting ability of DCs thus activating stronger CD8+ T-cell immunocidal responses.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

[Objective] To determine the feasibility of preparing plasminogen (Pg) with Fraction Ⅲ precipitation (hereinafter referred to as FⅢ-P) from low-temperature ethanol process by full chromatography (hereinafter referred to as FⅢ-P process). [Methods] The FⅢ-P was diluted with dissolution buffer at different dilution times and stirring time. The potency and antigen concentration of Pg in dissolution sample were detected and the dissolution and clarification conditions were determined. Pre-treatment of loading sample and pre-experiment of affinity chromatography were carried out on the FⅢ-P dissolution sample to judge whether the loading sample had an impact on the chromatography by observing the performance of the affinity chromatography column and to evaluate whether the affinity chromatography could achieve the purpose of purifying Pg by detecting the plasma protein antigen concentration and Pg potency of the samples in the process. Two batches of FⅢ-P process were studied step by step, and the specific activity, steps and total recovery, and the output of Pg per ton of plasma were calculated. The feasibility of preparing Pg by FⅢ-P process was evaluated by comparing with the data of full chromatography process using plasma as raw material (hereinafter referred to as plasma process). [Results] The FⅢ-P was dissolved with 10 times of dissolution buffer, stirred for 1 hour, centrifuged at room temperature of 10 000×g for 15 minutes. The supernatant was first filtered with a screen, then clarified with an 8/0.8 μm filter, and finally filtered with a 0.45/0.2 μm filter and loaded. Pre-test showed that from clarification and filtration to Pg affinity chromatography, the step recovery of activity and antigen was 39.51% and 108.64%, respectively, the antigen concentration of Pg increased by 31.16 times and the activity increased by 11.39 times after affinity chromatography, which reaching the effect of affinity chromatography purification of Pg. The results of 2 batches of step-by-step scale-up FⅢ-P process showed that the total recoveries of antigen and activity from plasma to SP chromatography of FⅢ-P process were (45.76±1.10)% and (24.15±0.59)%, respectively, which had a total loss of about 1/3 of antigen and about 2/3 of activity compared to the plasma process. The Pg specific activity of SP chromatography eluent was (4.68±0.25) U/mg, which was about half of that of plasma process, but meeted the internal standard of > 4 U/mg. The output of Pg antigen per ton of plasma in the FⅢ-P process was 68.73% of that in the plasma process, and the output of Pg activity per ton of plasma in the plasma process was 29.82% of that in the plasma process, which basically achieved the purpose of waste utilization of FⅢ-P. [Conclusion] The technical route of preparing Pg from FⅢ-P by full chromatography is feasible.

Objective To evaluate the pharmacokinetics characteristics of single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects.Methods This was a single-center,randomized,double-blind,placebo-controlled study.Twelve healthy adult Chinese subjects were randomized to receive single-dose of Etripamil nasal spray 70 mg(n=10)or placebo nasal spray(n=2).Blood and urine samples were collected prior and post dose.Etripamil in plasma and urine were analyzed by liquid chromatography-tandem mass spectrometry.The pharmacokinetic parameters were calculated by WinNonlin non-compartmental model.Results Following the single-dose of Etripamil nasal spray 70 mg in healthy adult Chinese subjects,the peak concentration of Etripamil in plasma was quickly attained,with a Cmax of(66.76±56.61)ng·mL-1 and a median(range)tmax of 4.00(3.00-5.00)min.The plasma concentrations of Etripamil had fallen approximately 65％from peak value at 25 min after dosing,and close to 80％within 50 min.The AUC0-last and AUC0-∞ were(3 104.16±2 654.46)and(4 048.77±2 682.38)ng·min·mL-1,respectively.The urine excretion percentage of Etripamil during 24 h was(0.01±0.01)％.Among the 12 subjects who were treated with Etripamil or placebo,10 subjects reported a total of 29 treatment-emergent adverse events(TEAEs).All of the TEAEs were mild in severity.The most common TEAEs were rhinorrhoea and lacrimation increased.Conclusion Etripamil was quickly absorbed after intranasal administration,followed by rapid distribution and elimination(not primarily excreted by renal);Etripamil 70 mg was safe and well tolerated by the healthy Chinese adult subjects.

Objective To establish a normal three-dimensional model of the hip bone in adolescents aged 10-19 years old,analyze the morphology and positional parameters of the posterior superior iliac spine of the hip bone among different genders,sides,and ages,which can supplement the study of the anatomical morphology of the hip bone and to provide a reference for the diagnosis of the clinically relevant diseases and for the therapeutic manipulation and localization of the hip bone.Methods Forty adolescent patients aged 10-19 years without previous spinal pelvic diseases were selected,and the pelvic CT image data were collected and imported into Mimics 21.0 software to establish the model.The relative position parameters of the posterior superior iliac spine and the surrounding anatomical landmarks included the length from the posterior superior iliac spine to the anterior superior iliac spine(ab),the length from the tip of the posterior superior iliac spine to the sciatica(ac),the length from the tip of the posterior superior iliac spine to the pubic tubercle(ae),the length from the tip of the posterior superior iliac spine to the midpoint of the posterior margin of the auricular joint surfaces(af),the length from the tip of the posterior superior iliac spine to the iliac spine turn(ag),and the length from the sciatica tubercle to the highest point of the iliac spine(cd).The local parameters of the posterior superior iliac spine included the width(W0)and the thickness(H0)at point A.The maximum width of the posterior iliac spine(WMAX),its distance from point a(D0),and the width of the iliac spine were measured at 0.5,1,and 1.5 cm from point a,and were recorded sequentially as W1,W2,and W3.The width of the iliac spine at the turn of the iliac spine(point g)was measured(W4).The relative positions and parameters of the posterior superior iliac spine to the surrounding anatomical landmarks and the localized parameters of the posterior superior iliac spine were compared sequentially for different genders,sides,and age groups.Results In the measurement result of the parameters of the posterior superior iliac spine and the surrounding anatomical landmarks,the differences in the comparisons between different genders of the ac,ae,and af indexes were statistically significant(P＜0.05),and the differences in the comparisons between different genders of the ab,ag,and cd indexes were not statistically significant(P＞0.05).The differences in the comparisons between the right and left sides of the ab,ac,ae,af,ag,and cd indexes were not statistically significant(P＞0.05).The difference in comparison between different age groups of ab,ac,ae,af,ag,and cd indicators was statistically significant(P＜0.05).In the measurement result of the local parameters of the posterior superior iliac spine,the difference in the comparison between the sexes of the W0,W1,W2,WMAX,and H0 indexes was statistically significant(P＜0.05),and the difference in the comparison between the sexes of the W3,W4,and D0 indexes was not statistically significant(P＞0.05);And the difference in the comparison between the left and right sides of the W0,W1,W2,and the right and left sides of the W3,W4,WMAX,D0,and H0 indexes was not statistically significant(P＞0.05);The difference between W0,W1,W2,W3,W4,WMAX,D0,H0 indicators compared between different age groups was not statistically significant(P＞0.05).Conclusion Adolescent females have overall greater pelvic parameters than males,with wider and thicker tips of the posterior superior iliac spine in females and narrower and thinner tips of the posterior superior iliac spine in males;Pelvic parameters show a tendency to increase with age,while the width and thickness of the posterior superior iliac spine,as well as the width of the cephalic end to the iliac spine remain essentially unchanged.

Objective To explore the solvent effect on the chromatographic retention performance by RP-HPLC in traditional Chinese medicine analysis.Methods Five traditional Chinese medicines were selected to determin by HPLC according to the requirements of each medicinal content determination item in Chinese pharmacopoeia(Vol.Ⅰ,2020),they were gentiopicroside-Radix gentianae,syringin-Acanthopanax enticosus,rosin diglucoside-Eucommia ulmoides,aesculin-Fraxinus Cortex,and adenosine-Cordyceps sinensis respectively.The effect of sample solvent in RP-HPLC was explored preliminarily on the chromatographic peak abnormalities and some solutions were proposed.Results The abnormal chromatographic retention behavior of the five traditional Chinese medicine components were characterized by retention time drift,peak broadening,extending and splitting,the fundamental reason for the above abnormal phenomenons was that there was a certain mismatch between the sample solvent and the mobile phase,leading to different existing forms of the sample between the sample solvent and the mobile phase(Solvent Effect).The results showed that the mobile phase or similar to mobile phase solution was a preferred method to reduce and eliminate solvent effect.In addition,reducing the injection volume or using the solvent effect eliminator can also be used as auxiliary means.Conclusion Solvent effect can cause abnormal peak shape,and had an influence on the accuracy of qualitative and quantitative results,it should be taken seriously in daily Chinese medicine analysis work.

Objective To design a novel oxygenator to solve the existing problems of extracorporeal membrane oxygenation(ECMO)machine in high transmembrane pressure difference,low efficiency of blood oxygen exchange and susceptibility to thrombosis.Methods The main body of the oxygenator vascular access flow field was gifted with a flat cylindrical shape.The topology of the vascular access was modeled in three dimensions,and the whole flow field was cut into a blood inlet section,an inlet buffer,a heat exchange zone,a blood oxygen exchange zone,an outlet buffer and a blood outlet section.The oxygenator was compared with Quadrox oxygenator by means of ANSYS FLUENT-based simulation and prototype experiments.Results Simulation calculations showed the oxygenator designed was comparable to the clinically used ones in general,and gained advantages in transmembrane pressure difference,blood oxygen exchange and flow uniformity.Experimental results indicated that the oxygenator behaved better than Quadrox oxygenator in transmembrane pressure difference and blood oxygen exchange.Conclusion The oxygenator has advantages in transmem-brane pressure difference,temperature change,blood oxygen ex-change and low probability of thrombosis.[Chinese Medical Equipment Journal,2024,45(3):23-28]