OBJECTIVE To investigate the establishment and promotion of a new standardized management model for anti- osteoporosis medication after fragility fracture surgery by resident clinical pharmacists， and provide references for resident pharmacists to carry out clinical pharmaceutical services. METHODS From July 2023 to March 2024，595 post-brittle fracture surgery patients were enrolled. Using the PDCA （plan-do-check-act） cycle，resident clinical pharmacists identified issues and conducted investigations in clinical practice. Through integrating clinical pharmacist intervention services before， during and after treatment， a medication treatment pathway was developed， thereby establishing a standardized management model for anti- osteoporosis treatment following fragility fracture surgery. Leveraging the National Brittle Fracture Big Data Platform （under the National Clinical Research Center for Orthopedics and Sports Rehabilitation）， a dedicated data module was constructed， providing big data support to evaluate the efficacy of this pharmaceutical care model. RESULTS Continuous PDCA cycle driven improvements significantly increased the proportion of osteoporosis diagnosis （from 9% before intervention to 81%） and proportion of drug treatment （from 4% to 75%）.The proportions of bone density and bone metabolism testing also rose markedly，positively impacting long-term patient outcomes. CONCLUSIONS The establishment of a standardized management model for anti- osteoporosis treatment following fragility fracture surgery by resident clinical pharmacists has enhanced clinicians’ diagnostic and therapeutic capabilities for osteoporosis， ensures rational medication use in osteoporosis patients， and demonstrates significant potential for widespread adoption and application.

Parkinson's disease(PD) is a neurodegenerative disorder characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra and the accumulation of Lewy bodies. While conventional drugs like levodopa can improve early symptoms, their efficacy diminishes over time, and they may cause severe side effects. Traditional Chinese medicine(TCM), with its multi-target therapeutic approach, has shown unique advantages in PD treatment, particularly in slowing disease progression and improving clinical symptoms. The nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) signaling pathway plays a critical role in cellular antioxidation, anti-inflammation, and cellular repair mechanisms, which are crucial for neuroprotection against PD. Studies indicate that TCM regulates the Nrf2/HO-1 pathway to enhance neuronal antioxidative capacity, inhibit neuroinflammation, promote dopaminergic neuron repair and survival, and slow pathological progression. This review explores the neuroprotective role of the Nrf2/HO-1 pathway in PD patients, including alleviating oxidative stress, suppressing neuroinflammation, promoting neuronal repair, and regulating iron metabolism and autophagy. It also discusses the mechanisms by which TCM active ingredients(flavonoids, alkaloids, terpenes, saponins, polyphenols, etc.), single herbs(Cistanche deserticola, Uraria crinite, and Melissa officinalis, etc.), and formulas(Bushen Jianpi Decoction, Didang Decoction, and Gancao Yangyin Decoction, etc.) modulate the Nrf2/HO-1 pathway in PD treatment, providing a theoretical basis for the clinical application and new drug development of TCM in PD prevention and treatment.
Humans ; Parkinson Disease/genetics* ; NF-E2-Related Factor 2/genetics* ; Signal Transduction/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Heme Oxygenase-1/genetics* ; Medicine, Chinese Traditional

OBJECTIVE: To explore the clinical efficacy and safety of the "Three-Step Nine-Method Lumbar Correction" combined with physical therapy in the treatment of patients with degenerative lumbar spondylolisthesis(DLS). METHODS: From January 2021 to December 2021, 72 patients diagnosed with DLS were enrolled and divided into the Three-Step Nine-Method Lumbar Correction group and the pelvic traction group, with 36 cases in each group. In the Three-Step Nine-Method Lumbar Correction group, there were 15 males and 21 females;aged 54 to 66 years old, with an average of (59.07±5.69) years old;the course of disease was 14 to 26 years old, with an average of (20.35±5.66) years old. They were treated with the Three-Step Nine-Method Lumbar Correction combined with low-frequency physical therapy, 3 times a week, for a 4-week course. In the pelvic traction group, there were 12 males and 24 females;aged 54 to 66 years old, with an average of (59.69±5.59) years old;the course of disease was 13 to 26 years old, with an average of (19.74±5.80) years old. They were treated with pelvic traction combined with low-frequency physical therapy. Efficacy evaluation was conducted using the visual analogue scale(VAS), Oswestry disability index(ODI), Japanese Orthopaedic Association (JOA) score, and Short Form 36 Health Survey (SF-36) before treatment, after 2 and 4 weeks of treatment, and at the 8-week follow-up after the end of treatment. In addition, imaging parameters of paravertebral muscles were evaluated before treatment and at the completion of treatment. RESULTS: All 72 patients completed the follow-up for 8 weeks. At the 8-week follow-up after the end of treatment, in the Three-Step Nine-Method Lumbar Correction group, the VAS score for low back pain decreased from (6.25±1.23) points before treatment to (1.25±0.65) points, with a statistically significant difference (P<0.05);the ODI decreased from (57.17±7.13)% before treatment to (19.89±5.66)%, with a statistically significant difference (P<0.05);the JOA score and SF-36 score increased from (15.46±3.20) points and (35.25±9.28) points before treatment to (23.75±2.10) points and (62.31±13.03) points, respectively, with statistically significant differences (P<0.05). The improvement of each index in the Three-Step Nine-Method Lumbar Correction group was better than that in the pelvic traction group (P<0.05), but the change in imaging parameters was not significant (P>0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05), and no serious adverse events occurred. CONCLUSION The Three-Step Nine-Method Lumbar Correction combined with physical therapy has a definite efficacy in the treatment of DLS. It can significantly relieve pain symptoms, improve physical function and patients' quality of life. Its effect is better than that of pelvic traction combined with physical therapy, and it has high safety. However, its improvement on paravertebral muscles is not obvious.
Humans ; Male ; Female ; Middle Aged ; Spondylolisthesis/physiopathology* ; Aged ; Prospective Studies ; Lumbar Vertebrae/physiopathology* ; Physical Therapy Modalities ; Adult

As polar cells, neurons are composed of a cell body, dendritic networks, and long, branched axons. To maintain normal physiological functions throughout the lifespan of vertebrates, differentiated neurons require substantial energy to sustain resting potential and synaptic transmission. Neurons predominantly rely on ATP generated through mitochondrial oxidative phosphorylation for energy. They transport and accumulate healthy mitochondria to energy-demanding areas, such as the presynaptic terminals of axon branches, through long-distance transport and anchoring, while reversing the transport of aged or damaged mitochondria in the axon terminals back to the soma for degradation. This article, integrating authors’ research, discusses from a mechanical perspective how mitochondria overcome resistance to achieve long-distance transport along axons under the influence of driving forces. The review covers topics such as microtubule polarity, microtubule motor proteins, mitochondrial docking protein complexes, interactions between mitochondria and anchoring proteins, intracellular resistance, interactions between mitochondria and the endoplasmic reticulum, and aspects of mitochondrial biogenesis, fission, fusion, division, and quality control. These novel perspectives will provide important insights for understanding neurological diseases caused by mitochondrial transport dysfunctions.

From the perspective of the physiological basis of liver and kidney sharing the common source in traditional Chinese medicine(TCM),and by integrating the theory of kidney dominating bone,liver dominating tendon,and meridian sinew of TCM as well as the bone resorption and collapse theory,and non-uniform settlement theory and lower-limb musculoskeletal bowstring structure theory of modern orthopedics,the pathogenesis of osteonecrosis of the femoral head(ONFH)under the system of non-uniform settlement during bone resorption and multidimensional composite bowstring working in coordination with the theory of liver-kidney and muscle-bone was explored.The key to the TCM pathogenesis of ONFH lies in the deficiency of the liver and kidney,and then the imbalance of kidney yin-yang leads to the disruption of the dynamic balance of bone formation and bone resorption mediated by osteoblasts-osteoclasts,which manifests as the elevated level of bone metabolism and the enhancement of focal bone resorption in the femoral head,and then leads to the necrosis and collapse of the femoral head.It is considered that the kidney dominates bone,liver dominates tendon,and the tendon and bone together constitute the muscle-bone-joint dynamic and static system of the hip joint.The appearance of collapse destroys the originally balanced muscle-bone-joint system.Moreover,the failure of liver blood in the nourishment of muscles and tendons further exacerbates the imbalance of the soft tissues around the hip joint,accelerates the collapse of the muscle-bone-joint dynamic and static system,speeds up the process of femoral head collapse,and ultimately results in irreversible outcomes.Based on the above pathogenesis,the systematic integrative treatment of ONFH should be based on the TCM holistic concept,focuses on the focal improvement of internal and external blood circulation of the femoral head by various approaches,so as to rebuild the coordination of joint function.Moreover,attention should be paid to the physical constitution of the patients,and therapy of tonifying the kidney and regulating the liver can be used to restore the balance between osteogenesis and osteoblastogenesis,and to reconstruct the muscle-bone-joint system,so as to effectively delay or even prevent the occurrence of ONFH.

Objective To explore the efficacy of early hyperbaric oxygen therapy(HBOT)combined with median nerve electrical stimulation(MNES)in the treatment of severe traumatic brain injury(sTBI)and its impact on hemodynamics,coma degree,and neurological function of patients.Methods A total of 78 patients with sTBI admitted to the General Hospital of Western Theater Command from March 2020 to October 2021 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 39 patients in each group.The patients in both groups underwent basic treatments such as water,electrolyte and acid-base balance,nutritional support,anti-infection,and decompressive craniectomy.On this basis,patients in the control group received early HBOT,while patients in the observation group received both HBOT and MNES.Their clinical efficacy was compared between the two groups.Before and after treatment,dual-channel transcranial Doppler ultrasound was performed to detect hemodynamic indicators such as peak systolic blood flow velocity(Vs),mean blood flow velocity(Vm),and pulsatility index(PI)in the middle cerebral artery of patients in the two groups.The Glasgow Coma Scale(GCS)score was used to evaluate the degree of coma of patients in the two groups,the National Institutes of Health Stroke Scale(NIHSS)score was used to assess the neurological deficits of patients in the two groups,and the enzyme-linked immunosorbent assay was used to measure the levels of central nervous system specific protein(S100-β),glial fibrillary acidic protein(GFAP),and myelin basic protein(MBP).Complications during treatment of patients in the two groups were recorded,and their incidence was compared.Results The total effective rate of patients in the control and observation groups was 79.49％(31/39)and 92.31％(36/39),respectively.The total effective rate in the observation group was significantly higher than that in the control group(x2=8.971,P＜0.05).There was no significant difference in Vm,Vs,and PI between the two groups before treatment(P＞0.05).After treatment,the Vm and Vs in both groups were significantly higher than those before treatment,while the PI was significantly lower than that before treatment(P＜0.05);and the Vm and Vs in the observation group were signifi-cantly higher than that those in the control group,while the PI was significantly lower than that in the control group(P＜0.05).There was no significant difference in GCS and NIHSS scores between the two groups before treatment(P＞0.05).After treatment,the GCS score in both groups was significantly higher than that before treatment,while the NIHSS score was significantly lower than that before treatment(P＜0.05);and the GCS score in the observation group was significantly higher than that in the control group,while the NIHSS score was significantly lower than that in the control group(P＜0.05).There was no significant difference in S100-β,GFAP,and MBP levels between the two groups before treatment(P＞0.05).After treatment,the S100-β,GFAP,and MBP levels in both groups were significantly lower than those before treatment(P＜0.05),and the S100-β,GFAP,and MBP levels in the observation group were significantly lower than those in the control group(P＜0.05).During treatment,the incidence of complications in the control and observation groups was 23.08％(9/39)and 20.51％(8/39),respectively,showing no significant difference(x2=2.328,P＞0.05).Conclusion Early HBOT combined with MNES shows good efficacy in treating sTBI,which can effectively improve the patients'hemodynamic level,alleviate the severity of coma,enhance neurological function,and promote early recovery of consciousness,without increased risk of complications.

Berberine (BBR) is the main pharmacological active ingredient of Coptidis, which has hypoglycemic effect, but its clinical application is limited due to its poor oral bioavailability. Polyphenols, derived from cinnamon, are beneficial for type 2 diabetes mellitus (T2DM). The combination of both may have an additive effect. The aim of this study was to investigate the hypoglycemic effect and mechanism of combined medication in diabetic rats. The modeling rats were randomly divided into 5 groups (berberine group, cinnamon group, combined group, metformin group, diabetic control group) and normal control group. The animal experiments were approved by the Animal Ethics Committee (approval number: HMUIRB2022003). The subjects were given orally, and the control group was given equal volume solvent and body weight was measured weekly. Thirty days after administration, oral glucose tolerance test and insulin sensitivity test were performed, and fasting blood glucose (FBG), glycated serum protein (GSP), and serum insulin (INS) levels were detected; high-throughput sequencing technology was used to detect intestinal microbiota structure; real-time quantitative PCR (RT-qPCR) and Western blot were used to detect G protein-coupled receptor 5 (TGR5) and glucagon-like peptide-1 (GLP-1) expression levels. The results showed that, compared with the diabetic control group, the levels of FBG (P < 0.01) and GSP (P < 0.01) in the combined group were lower, and the insulin resistance was improved, which was better than that in the berberine group. Combined treatment increased the relative abundance of Bacteroides, Prevotella and Lactobacillus, reversed the decrease in Lactobacillus in the berberine alone induction group, and the combination of the two could promote the expression of TGR5 and GLP-1. In summary, the combined application of cinnamon and berberine can regulate glucose metabolism better than the application of berberine alone. Berberine combined with cinnamon can improve the function of pancreatic islet β cells in diabetes mellitus type 2 rats by changing the intestinal microbiota, increasing the expression of TGR5 and GLP-1 proteins, and thereby better regulating glucose metabolism.

In addition to providing energy for cells, mitochondria also participate in calcium homeostasis, cell information transfer, cell apoptosis, cell growth and differentiation. Therefore, maintaining mitochondrial homeostasis is very crucial for the body to carry out normal life activities. Ubiquitination, a post-translational modification of proteins, is involved in various physiological and pathological processes of cells by regulating mitochondrial homeostasis. However, the mechanism by which ubiquitination regulates mitochondrial homeostasis has not been summarized, especially the effect of Parkin protein on cardiovascular diseases. In this paper, the specific mechanism of mitochondrial homeostasis regulated by ubiquitination of Parkin protein is discussed, and the influence of mitochondrial homeostasis imbalance on cardiovascular diseases is reviewed, with a view to providing potential therapeutic strategies for the clinical treatment of cardiovascular diseases.

Objective To develop effective measures to reduce antibiotic use duration in very low birth weight(VLBW)preterm infants in the neonatal intensive care unit through quality improvement methods.Methods The study population consisted of hospitalized VLBW preterm infants,with the percentage of hospitalization time during which antibiotics were used from November 2020 to June 2021 serving as the baseline.The specific quality improvement goal was to reduce the duration of antibiotic use.Factors affecting antibiotic use duration in preterm infants were analyzed using Pareto charts.Key drivers were identified,and specific interventions were formulated based on the stages of antibiotic use.Changes in the percentage of antibiotic use duration were monitored with run charts until the quality improvement target was achieved.Results From November 2020 to June 2021,the baseline antibiotic use duration percentage was 49%,with a quality improvement target to reduce this by 10%within 12 months.The Pareto analysis indicated that major factors influencing antibiotic duration included non-standard antibiotic use;delayed cessation of antibiotics when no infection evidence was present;prolonged central venous catheter placement;insufficient application of kangaroo care;and delayed progress in enteral nutrition.The interventions implemented included:(1)establishing sepsis evaluation and management standards;(2)educating medical staff on the rational use of antibiotics for preterm infants;(3)supervising the enforcement of antibiotic use standards during ward rounds;(4)for those without clear signs of infection and with negative blood cultures,discontinued the use of antibiotics 36 hours after initiation;(5)reducing the duration of central venous catheterization and parenteral nutrition to lower the risk of infection in preterm infants.The control chart showed that with continuous implementation of interventions,the percentage of antibiotic use duration was reduced from 49%to 32%,a statistically significant decrease.Conclusions The application of quality improvement tools based on statistical principles and process control may significantly reduce the antibiotic use duration in VLBW preterm infants.

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer (CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR, respectively. Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p. The protein expressions of p53 and unc-51 like kinase 2 (ULK2) in CRC cells were detected by western blot. Flow cytometry was used to detect cell cycle and apoptosis. Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage. CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner, and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine. Moreover, ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues. Interestingly, ULK2 inhibited CRC cell proliferation in a p53-dependent manner. Furthermore, exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC, which may offer promising targets for CRC prevention and therapy.