BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

BACKGROUND:Currently,treatment method for knee osteoarthritis includes oral medicine,joint cavity drug injection,and physiotherapy,but the curative effect is limited.Existing studies have confirmed that silicon-based bioceramics can promote cartilage and subchondral bone repair and vascular regeneration.OBJECTIVE:To explore the effect of different concentrations of silicon-based bioceramics injected into the knee joint cavity in the treatment of knee osteoarthritis in rats.METHODS:Silicon-based bioceramics-calcium silicate was prepared.Twenty-five SD rats were randomly divided into five groups,with five rats in each group.The healthy group did not receive any intervention,and the modeling group,low-dose calcium silicate group,high-dose calcium silicate group,and saline group used anterior cruciate ligament transection to establish bilateral knee osteoarthritis models.Four weeks after modeling,0.05 mL of 50 and 100 mg/mL calcium silicate solution were injected into the knee joint cavity in the low-dose calcium silicate group and high-dose calcium silicate group,respectively,and 0.05 mL of saline was injected into the knee joint cavity in the saline group,once a week for 4 consecutive weeks.In the fifth week of administration,bilateral knee joint Micro-CT detection,knee joint cartilage hematoxylin-eosin staining,and modified Mankin score were performed.RESULTS AND CONCLUSION:(1)Micro-CT quantitative analysis showed that compared with the healthy group,the volume fraction and number of trabeculae of the medial tibial plateau in the modeling group decreased(P＜0.05),and the separation of trabeculae increased(P＜0.05).Compared with the modeling group,the volume fraction and number of trabeculae of the medial tibial plateau in the low-dose calcium silicate group and the saline group increased(P＜0.05),and the separation of trabeculae decreased(P＜0.05).(2)Hematoxylin-eosin staining showed that the cartilage surface of the healthy group and the low-dose calcium silicate group was relatively smooth and flat,the chondrocytes were evenly distributed,without clustered chondrocytes,the tide line was complete,and the staining was uniform;the cartilage surface of the high-dose calcium silicate group was slightly uneven,the middle and deep cells were disordered,with a small number of clustered chondrocytes,the tide line was discontinuous,and the staining was uneven;the cartilage surface of the saline group and the modeling group was obviously rough,the cells were disordered,with a large number of clustered chondrocytes,the tide line disappeared,and the staining was uneven.The modified Mankin score of the healthy group was lower than that of the high-dose calcium silicate group,the saline group,and the modeling group(P＜0.05).The modified Mankin score of the high-dose calcium silicate group and the low-dose calcium silicate group was lower than that of the saline group and the modeling group(P＜0.05).(3)The results show that calcium silicate knee joint injection has a certain effect in the treatment of knee osteoarthritis.Compared with 100 mg/mL calcium silicate solution,50 mg/mL calcium silicate solution can promote the recovery of subchondral bone and cartilage.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

Objective To report the diagnosis of a canine distemper virus outbreak among a colony of cynomolgus monkeys at an experimental monkey farm in 2019. MethodsA total of 46 samples were collected from 21 diseased cynomolgus monkeys (exhibiting symptoms such as facial rash, skin scurf, runny nose, and diarrhea) and from one deceased monkey at an experimental monkey breeding farm in South China in late 2019, including serum, skin rash swabs, and anticoagulated whole blood, liver, lung, and skin tissues were submitted for testing. All submitted samples were tested for canine distemper virus gene fragments using real-time quantitative PCR, while immunohistochemical staining was performed to detect canine distemper virus nucleoprotein in lung tissues. The skin tissue of the deceased monkey was ground and sieved. The filtrate was inoculated into a monolayer MDCK cell line for virus isolation. Then, whole-genome sequencing was performed to identify the isolated virus. The Clustal Omega tool was used to align and analyze the homology of different Asian canine distemper virus isolates. A phylogenetic tree was constructed, followed by genetic evolutionary analysis. ResultsClinical retrospective analysis revealed that the diseased cynomolgus monkeys exhibited symptoms similar to those observed in cynomolgus monkeys infected with measles virus. Necropsy findings showed red lesions in the lungs and significant hemorrhage in the colonic mucosa. Real-time quantitative PCR detected canine distemper virus nucleic acid in the serum, skin rash swabs of the infected monkeys, and various tissue samples of the deceased monkey, all of which tested positive. Calculation based on the standard curve formula indicated the viral load was highest in the skin tissue. Immunohistochemical staining of the deceased monkey's lung tissue demonstrated aggregation of CDV nucleoprotein in alveolar epithelial cells, bronchi, and bronchioles. A CDV strain was isolated from the skin tissue of the deceased monkey. Phylogenetic analysis indicated that this strain shares the closest relationship (98.86%) with the Asian-1 type canine distemper virus strain CDV/dog/HCM/33/140816, previously identified in dogs in Vietnam. ConclusionBased on comprehensive analysis of clinical symptoms, nucleic acid detection, viral protein immunohistochemistry, and whole-genome sequencing results, the diagnosis confirms that the cynomolgus monkeys in this facility are infected with canine distemper virus. It is recommended to include canine distemper virus as a routine surveillance target in captive monkey populations. Additionally, this study provides a foundation for further research on the molecular biological characteristics of canine distemper virus.

OBJECTIVE To investigate the induction of apoptosis in hepatocellular carcinoma cells by polyphyllin 9 （PP9） through the regulation of the Fas/Fas ligand （FasL） signaling pathway， and its inhibitory effect on the growth of transplanted tumor in nude mice. METHODS Based on the screening of cell lines and intervention conditions， HepG2 cells were selected as the experimental subject to investigate the effects of 2 μmol/L and 4 μmol/L PP9 treatment on cell colony formation activity， apoptosis rate， as well as the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3. Additionally， Fas inhibitor KR- 33493 was introduced to investigate the underlying mechanism of PP9’s anti-hepatocellular carcinoma activity. Using HepG2 cell tumor-bearing nude mice model as the object， and 5-fluorouracil （20 mg/kg） as the positive control， the effects of 10 mg/kg PP9 on tumor volume， tumor mass， and the protein expressions of the nuclear proliferation-associated antigen Ki-67 and cleaved caspase-3 in tumor-bearing nude mice were investigated. RESULTS Compared with the control group， 2， 4 μmol/L PP9 significantly decreased the number of clones and the clone formation rate of cells， but significantly increased the apoptosis rate， the protein expressions of Fas， FasL， cleaved caspase-8 and cleaved caspase-3 （P＜0.05 or P＜0.01）. However， the combination of Fas inhibitor KR-33493 could significantly reverse the effect of PP9 on the up-regulation of proteins related to the Fas/FasL signaling pathway （P＜0.01）. Compared with the control group， the tumor volume （on day 27）， mass and protein expression of Ki- 67 in nude mice of the PP9 group were significantly decreased， while the protein expression of cleaved caspase-3 was significantly increased （P＜0.01）. CONCLUSIONS PP9 can induce apoptosis of HepG2 cells by activating the Fas/FasL signaling pathway. Meanwhile， PP9 can also effectively inhibit the growth of transplanted tumors in nude mice.

OBJECTIVE To investigate the effectiveness of resident clinical pharmacist-led medication therapy management （MTM） model in geriatric cardiology departments， and provide reference for optimizing resident pharmaceutical services. METHODS A retrospective cohort study was conducted， incorporating data from inpatients admitted to the Department of Cardiovascular Medicine in the Geriatric Medical Center of our hospital during March to August 2023 （conventional group， n＝ 903） and the same period in 2024 （MTM group， n＝963）. The conventional group received only standard pharmaceutical services （including prospective prescription review and retrospective order evaluation）， while the MTM group received additional resident clinical pharmacist-led interventions-such as medication reconciliation， personalized therapeutic drug monitoring （TDM）， standardized intravenous infusion management， and a four-stage closed-loop monitoring process-based on conventional care. The effectiveness of the MTM model was evaluated by comparing the primary outcome measures （e.g.， intravenous infusion rate， TDM target attainment rate） and secondary outcome measures [e.g.， incidence of drug-drug interactions （DDIs）， incidence of grade 3 or higher acute kidney injury， average length of hospital stay， cholesterol， and medication cost per capita] between the two groups. RESULTS Compared with the conventional group， in terms of primary outcome indexes： both the overall intravenous infusion rate and the use rate of acid-suppressive injection were significantly lowered in the MTM group （P＜0.05）； serum concentration target attainment rates for digoxin and vancomycin were increased significantly （P＜0.05）. For secondary outcome indexes， the MTM group exhibited significant decreases in the work incidence of grade 3 or higher acute kidney injury， the incidence of DDIs， the rate of patients leaving the hospital against medical advice， alanine amino-transferase， aspartate transferase and the per capita total medication cost （P＜0.05）. Additionally， there was a notable increase in the creatinine， estimated glomerular filtration rate and a significant shortening of the per capita length of hospital stay （P＜0.05）. CONCLUSIONS The resident clinical pharmacist-led MTM model can significantly optimize medication therapy processes， enhance medication safety and cost-effectiveness， thus playing a positive role in promoting rational drug use and improving patient outcomes.

This article reviewed the progress in military operational medicine in the U.S.Armed Forces in 2024 in terms of improved capabilities of health care in extreme natural environments,protection from noise damage,sleep interventions,intelligence monitoring of operational efficiency and more academic exchanges in this field.These measures are intended to improve the operational performance of soldiers in every possible way.This article is expected to provide useful references for related research.

Skin wound repair is critically regulated by peripheral nerves. Injury or dysfunction of these nerves represents a key factor impairing the healing of pathological wounds, such as diabetic ulcers and deep burns. The mechanisms by which peripheral nerves participate in cutaneous wound healing primarily involve modulation of immune responses, construction of stem cell niches, and promotion of angiogenesis. Sensory neurons initiate and mediate essential local immune responses, contribute to the epidermal stem cell microenvironment, and support regenerative potential. Sympathetic nerves bidirectionally regulate immune homeostasis via the release of various neuromodulators and precisely control the activation of hair follicle stem cells as well as the homeostasis of melanocyte stem cells. Schwann cells also play pivotal roles in immune modulation, balancing repair processes and mitigating scar formation. During revascularization, sensory and autonomic nerve terminals release neurotransmitters that precisely regulate vasomotor activity and angiogenesis, while Schwann cells facilitate the reconstruction of functional vascular networks via potent paracrine signaling. This review systematically summarizes the crucial roles of peripheral nerves in skin wound repair, with emphasis on their regulatory mechanisms in immune responses, stem cell activation and homeostasis, and vascular dynamics, thereby providing insights into the development of novel therapeutic strategies targeting peripheral nerve regulation.
Humans ; Wound Healing/physiology* ; Peripheral Nerves/physiology* ; Schwann Cells/physiology* ; Skin/injuries* ; Animals

Objective:To investigate the effect and mechanism of lycium barbarum polysaccharide(LBP)on lipopolysaccharide(LPS)-induced inflammatory response of NLRP3 inflammasome in BV2 microglial cells.Methods:BV2 microglial cells were routinely cultured.CCK-8 assay was used to detect the effect of different concentrations(0.5,1,1.5,2 g/L)LBP on cell activity.Cells were di-vided into three groups:control group,LPS group and LBP+LPS group.Effect of LBP on LPS-induced cell activity was detected by CCK-8 method;RT-qPCR and immunofluorescence assay were used to detect NLRP3,ASC,Caspase-1,IL-18 and IL-1β expressions.Western blot was used to detect expressions of NLRP3,ASC,Caspase-1,TLR4,MyD88,NF-κB p65,IL-18,IL-1β and TNF-α pro-teins.Results:CCK-8 assay showed that 1 g/L LBP was the most applicable.Compared with control group,cell viability in LPS group was decreased;RT-qPCR,immunofluorescence and Western blot results showed that fluorescence intensity,mRNA and protein expres-sions of NLRP3,ASC,Caspase-1,IL-18 and IL-1β were increased in LPS group.Western blot results showed that TLR4,MyD88,NF-κB p65 and TNF-α protein expressions were increased in LPS group.After LBP treatment,cell viability was increased;expres-sions of NLRP3,ASC,Caspase-1,NF-κB p65,TLR4,MyD88,IL-18,IL-1β and TNF-α were decreased.Conclusion:LBP may in-hibit LPS-induced NLRP3 inflammatory vesicles in BV2 cells via TLR4/MyD88/NF-κB signaling pathway.

Objective To investigate the intervention effects and mechanism of Danggui Shaoyao power on spontaneous abortion rats.Methods A total of 60 first-day pregnant rats were randomly divided into normal group,model group,dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups,with 10 rats in each group.The low,middle,and high dose groups were given Danggui Shaoyao power 5.175 g·kg-1,10.35 g·kg-1,20.7 g·kg-1,respectively,from 1 to 12 days of gestation,and the dydrogesterone group was given dydrogesterone tablet solution 2 mg·kg-1 once a day.On the 13th day of gestation,rats model of spontaneous abortion was established by intragastric administration of 5 mg·kg-1 of mifepristone tablet solution except for the normal group.Serum levels of GnRH,FSH,LH,E2 were measured,and abortion rates and uterine coefficients were calculated.The pathological changes of pregnant uterus were observed by haematoxylin-eosin(HE)staining.The differential proteins in rats pregnant uterus were detected by Label-Free shotgun proteomic technique,and the PPI,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways analysis of the differential proteins were analyzed.Immunohistochemistry was used to verify the expression levels of differential proteins.Results Compared with normal group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were decreased,and the abortion rates were increased in model group(P<0.05).There were abortion lesions of spontaneous abortion in model group.Compared with model group,the serum levels of GnRH,FSH,LH,E2 and uterine coefficients were increased(P<0.05),and the abortion rates were decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Proteomic results showed that a total of 550 proteins were quantified in this study.PPI analysis showed that a total of 159 proteins interacted with other proteins as hubs;the results of GO and KEGG enrichment analysis showed that the intervention effect of Danggui Shaoyao power on spontaneous abortion is related to the focal adhesion pathway,and involved upregulation of Akt2,Col6a1,Col6a2 and downregulation of Pten.Immunohistochemistry results showed that compared with normal group,the expression level of Akt2,Col6a1 and Col6a2 were decreased(P<0.05),and the expression level of Pten was increased(P<0.05)in model group.Compared with model group,the expression level of Akt2,Col6a1 and Col6a2 were increased(P<0.05),and the expression level of Pten was decreased(P<0.05)in dydrogesterone group and Danggui Shaoyao power low,middle,and high dose groups.Conclusions Danggui Shaoyao power has the intervention effect on spontaneous abortion,and its mechanism may be related to by demoting the protein expressions of Pten,and promoting the protein expressions of Akt2,Col6a1 and Col6a2.