Objective:To investigate the effects of musculoskeletal ultrasound(MSUS)-guided shoulder joint capsule hydraulic expansion method combined with rotator interval(RI)injection method on ultrasound imaging indicators,shoulder function,and serum inflammatory factors in treating patients with early primary frozen shoulder(PFS).Methods:A total of 168 patients with early PFS admitted to Jiangbei District of The Frist Affiliated Hospital to Army Medical University between June 2021 and June 2023 were selected.They were randomly divided into a control group and an observation group by using a random number table,with 84 patients in each group.The control group received the therapy with MSUS-guided shoulder joint capsule hydraulic expansion.The observation group received the therapy with RI injection on the basis of the control group.After 5 weeks of treatment,the changes of the following parameters were compared and analyzed between the two groups:Visual Analog Scale(VAS)score for shoulder pain,Simple Shoulder Test(SST)score,Constant-Murley Score(CMS),thickness of the glenohumeral joint capsule at the axilla of ultrasound imaging,thickness of coracohumeral ligament(CHL),RI thickness,positivity rate of RI blood flow,passive range of motion(ROM)of the shoulder joint,and serum inflammatory factor levels including tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)and interleukin-6(IL-6).Results:At 5th week after treatment,both groups showed VAS scores decreased,and SST and CMS scores increased.The VAS score(1.34±0.30)of observation group was significantly lower than(1.97±0.46)of control group,and the SST score and CMS score were significantly higher than those of control group(t=10.514,9.597,7.910,P<0.05),respectively.Both groups showed decreases in thickness of the glenohumeral joint capsule at the axilla,CHL thickness,RI thickness,and positivity rate of RI blood flow,and these indicators of observation group were significantly lower than them of control group,with statistically significant differences(t=5.518,16.106,9.050,25.211,P<0.05).The ranges of backward extension and outward rotation of observation group were larger than those of control group,and the differences were statistically significant(t=9.209,12.447,P<0.05).The serum levels of TNF-α,IL-6 and CRP of observation group were significantly lower than those of control group,and the differences were statistically significant(t=10.523,17.750,19.995,P<0.05),respectively.Conclusion:The treatment of MSUS-guided shoulder joint capsule hydraulic expansion combined with RI injection can effectively alleviate the degrees of shoulder pain and dysfunction in patients with early PFS,and improve indicators of ultrasound imaging,the ROM values of outward rotation and backward extension,and reduce serum levels of inflammatory factors,which have favorable therapeutic effects.

Age-related macular degeneration(AMD)is a disease that affects the vision of elderly individuals worldwide.Although current therapeutics have shown effectiveness against AMD,some patients may remain unresponsive and continue to experience disease progression.Therefore,in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment.Recently,studies have suggested that dysfunction of mitochondria can lead to the ag-gregation of reactive oxygen species(ROS)and activation of the cyclic GMP-AMP synthase(cGAS)/stimulator of interferon genes(STING)innate immunity pathways,ultimately resulting in sterile inflammation and cell death in various cells,such as cardiomyocytes and macrophages.Therefore,combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management.Notably,emerging evidence indicates that natural products targeting mitochondrial quality control(MQC)and the cGAS/STING innate immunity pathways exhibit promise in treating AMD.Here,we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways,as well as their interconnected mediators,which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses,thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Age-related macular degeneration (AMD) is a disease that affects the vision of elderly individuals worldwide. Although current therapeutics have shown effectiveness against AMD, some patients may remain unresponsive and continue to experience disease progression. Therefore, in-depth knowledge of the mechanism underlying AMD pathogenesis is urgently required to identify potential drug targets for AMD treatment. Recently, studies have suggested that dysfunction of mitochondria can lead to the aggregation of reactive oxygen species (ROS) and activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) innate immunity pathways, ultimately resulting in sterile inflammation and cell death in various cells, such as cardiomyocytes and macrophages. Therefore, combining strategies targeting mitochondrial dysfunction and inflammatory mediators may hold great potential in facilitating AMD management. Notably, emerging evidence indicates that natural products targeting mitochondrial quality control (MQC) and the cGAS/STING innate immunity pathways exhibit promise in treating AMD. Here, we summarize phytochemicals that could directly or indirectly influence the MQC and the cGAS/STING innate immunity pathways, as well as their interconnected mediators, which have the potential to mitigate oxidative stress and suppress excessive inflammatory responses, thereby hoping to offer new insights into therapeutic interventions for AMD treatment.

Background and Aims:Pancreatic cancer is a highly malignant digestive system tumor characterized by poor prognosis and limited therapeutic response.The tumor microenvironment plays a crucial role in its progression,where oxidative stress and lactate metabolism are two tightly interconnected processes influencing tumor growth,immune escape,and therapeutic resistance.However,their combined prognostic impact remains poorly understood.This study aimed to integrate oxidative stress-and lactate metabolism-related genes to establish and validate a robust prognostic model for pancreatic cancer,and to explore its association with immune microenvironment characteristics.Methods:Transcriptomic and clinical data of 177 pancreatic cancer patients were obtained from TCGA database and an external validation was performed using the GEO dataset(GSE57495).Differentially expressed genes associated with oxidative stress and lactate metabolism were identified using the"limma"package.Univariate Cox regression was used to screen prognostic genes,followed by LASSO regression to construct a multi-gene risk model.Model performance was evaluated by Kaplan-Meier survival analysis,receiver operating characteristic(ROC)curves,concordance index(C-index),nomogram calibration,and decision curve analysis(DCA).The CIBERSORT and ssGSEA algorithms were used to analyze immune cell infiltration and immune functional differences between risk groups.Results:A six-gene signature(MUC1,KRT18,SDC1,AREG,DDC,and ATPAF2)was identified to construct the prognostic model.Based on the calculated risk score,patients were stratified into high-and low-risk groups.Kaplan-Meier analysis revealed significantly worse overall survival in the high-risk group(P<0.01).The model showed good predictive accuracy with 1-,2-,and 3-year AUCs of 0.710,0.674,and 0.649,respectively.The C-index and calibration curves confirmed its reliability,and multivariate Cox regression indicated that the risk score was an independent prognostic factor.External validation using GEO data demonstrated consistent predictive performance.Immune infiltration analysis revealed that M0 macrophages were markedly enriched in the high-risk group,while cytotoxic and effector T-cell populations were reduced,suggesting that an immunosuppressive microenvironment may contribute to poor outcomes.Conclusion:This study developed and validated a novel prognostic model for pancreatic cancer based on oxidative stress and lactate metabolism-related genes.The model accurately predicts patient survival,reflects immune microenvironment heterogeneity,and provides new molecular insights for risk stratification and individualized therapeutic strategies in pancreatic cancer management.

Background and Aims:Pancreatic cancer is a highly malignant digestive system tumor characterized by poor prognosis and limited therapeutic response.The tumor microenvironment plays a crucial role in its progression,where oxidative stress and lactate metabolism are two tightly interconnected processes influencing tumor growth,immune escape,and therapeutic resistance.However,their combined prognostic impact remains poorly understood.This study aimed to integrate oxidative stress-and lactate metabolism-related genes to establish and validate a robust prognostic model for pancreatic cancer,and to explore its association with immune microenvironment characteristics.Methods:Transcriptomic and clinical data of 177 pancreatic cancer patients were obtained from TCGA database and an external validation was performed using the GEO dataset(GSE57495).Differentially expressed genes associated with oxidative stress and lactate metabolism were identified using the"limma"package.Univariate Cox regression was used to screen prognostic genes,followed by LASSO regression to construct a multi-gene risk model.Model performance was evaluated by Kaplan-Meier survival analysis,receiver operating characteristic(ROC)curves,concordance index(C-index),nomogram calibration,and decision curve analysis(DCA).The CIBERSORT and ssGSEA algorithms were used to analyze immune cell infiltration and immune functional differences between risk groups.Results:A six-gene signature(MUC1,KRT18,SDC1,AREG,DDC,and ATPAF2)was identified to construct the prognostic model.Based on the calculated risk score,patients were stratified into high-and low-risk groups.Kaplan-Meier analysis revealed significantly worse overall survival in the high-risk group(P<0.01).The model showed good predictive accuracy with 1-,2-,and 3-year AUCs of 0.710,0.674,and 0.649,respectively.The C-index and calibration curves confirmed its reliability,and multivariate Cox regression indicated that the risk score was an independent prognostic factor.External validation using GEO data demonstrated consistent predictive performance.Immune infiltration analysis revealed that M0 macrophages were markedly enriched in the high-risk group,while cytotoxic and effector T-cell populations were reduced,suggesting that an immunosuppressive microenvironment may contribute to poor outcomes.Conclusion:This study developed and validated a novel prognostic model for pancreatic cancer based on oxidative stress and lactate metabolism-related genes.The model accurately predicts patient survival,reflects immune microenvironment heterogeneity,and provides new molecular insights for risk stratification and individualized therapeutic strategies in pancreatic cancer management.

Objective:To investigate the effects of musculoskeletal ultrasound(MSUS)-guided shoulder joint capsule hydraulic expansion method combined with rotator interval(RI)injection method on ultrasound imaging indicators,shoulder function,and serum inflammatory factors in treating patients with early primary frozen shoulder(PFS).Methods:A total of 168 patients with early PFS admitted to Jiangbei District of The Frist Affiliated Hospital to Army Medical University between June 2021 and June 2023 were selected.They were randomly divided into a control group and an observation group by using a random number table,with 84 patients in each group.The control group received the therapy with MSUS-guided shoulder joint capsule hydraulic expansion.The observation group received the therapy with RI injection on the basis of the control group.After 5 weeks of treatment,the changes of the following parameters were compared and analyzed between the two groups:Visual Analog Scale(VAS)score for shoulder pain,Simple Shoulder Test(SST)score,Constant-Murley Score(CMS),thickness of the glenohumeral joint capsule at the axilla of ultrasound imaging,thickness of coracohumeral ligament(CHL),RI thickness,positivity rate of RI blood flow,passive range of motion(ROM)of the shoulder joint,and serum inflammatory factor levels including tumor necrosis factor-α(TNF-α),C-reactive protein(CRP)and interleukin-6(IL-6).Results:At 5th week after treatment,both groups showed VAS scores decreased,and SST and CMS scores increased.The VAS score(1.34±0.30)of observation group was significantly lower than(1.97±0.46)of control group,and the SST score and CMS score were significantly higher than those of control group(t=10.514,9.597,7.910,P<0.05),respectively.Both groups showed decreases in thickness of the glenohumeral joint capsule at the axilla,CHL thickness,RI thickness,and positivity rate of RI blood flow,and these indicators of observation group were significantly lower than them of control group,with statistically significant differences(t=5.518,16.106,9.050,25.211,P<0.05).The ranges of backward extension and outward rotation of observation group were larger than those of control group,and the differences were statistically significant(t=9.209,12.447,P<0.05).The serum levels of TNF-α,IL-6 and CRP of observation group were significantly lower than those of control group,and the differences were statistically significant(t=10.523,17.750,19.995,P<0.05),respectively.Conclusion:The treatment of MSUS-guided shoulder joint capsule hydraulic expansion combined with RI injection can effectively alleviate the degrees of shoulder pain and dysfunction in patients with early PFS,and improve indicators of ultrasound imaging,the ROM values of outward rotation and backward extension,and reduce serum levels of inflammatory factors,which have favorable therapeutic effects.

OBJECTIVE To investigate the in vitro inhibitory mechanism of berberine on the proliferation of tumor stem cells and evaluate its in vivo safety. METHODS Flow cytometry was used to select tumor stem cells from mouse skin melanoma B16F10 cells； CD44， CD133， Nanog homologous box protein （NANOG） and octamer-binding transcription factor 4 （OCT4） were used as indicators to characterize tumor stem cells. Tumor stem cells were divided into control group， all-trans retinoic acid （ATRA） group， and berberine group， and the CCK-8 method was used to detect the effects of berberine on the viability of tumor stem cells； flow cytometry was adopted to detect cell apoptotic rate， the proportion of CD44+/CD133+ and the positive cell rate of sex determining region Y box protein 2 （SOX2）； the morphological changes of tumor balls were recorded after treatment with berberine； the morphology of cell pyroptosis in each group was recorded， and the release rate of lactate dehydrogenase （LDH） was detected； Western blot assay was adopted to detect the expressions of pyroptosis-related protein gasdermin E （GSDME）， GSDME- N， caspase-3 and cleaved caspase-3. Preliminary evaluation of in vivo safety of berberine was conducted by using zebrafish embryo toxicity experiments. RESULTS Compared with B16F10 cells， the proportion of CD44+/CD133+ cells in tumor stem cells and the fluorescence intensity of NANOG and OCT4 were significantly increased （P＜0.000 1）. The half-inhibitory concentration of berberine to tumor stem cells was 50.98 μmol/L. Compared with the control group， the apoptotic rate of cells in the berberine group was significantly increased， while the proportion of CD44+/CD133+ cells and the rate of SOX2 positive cells were reduced significantly （P＜0.000 1）； tumor stem cell spheroids were atrophied， with partial cell death. After treatment with berberine， tumor stem cells exhibited swelling in their outermost layer， the release rate of LDH of cells was significantly increased and the release rate of LDH increased with increasing dose； the protein expressions of GSDME-N and cleaved-caspase-3 of cells in berberine 20， 40 μmol/L groups were significantly increased， and the protein expressions of GSDME and caspase-3 were significantly reduced （except for berberine 20 μmol/L group， P＜0.05）. The embryonic development of zebrafish treated with berberine was almost unaffected， and the survival rate of embryo reached 100%， with no obvious abnormalities observed. CONCLUSIONS Berberine has good activity against the proliferation of tumor stem cells， and its mechanism of action may be related to activating GSDME and promoting cell pyroptosis； berberine has good in vivo safety.

Background Heavy metal emissions from mining and smelting areas are a global problem, and health risks associated with heavy metal contamination of soils are of great concern. The long-term mining of the largest realgar mine in Asia has caused severe arsenic and other metal pollution to the surrounding rivers and soils. Objective To understand the levels of metal contamination and health risks in agricultural soils of villages surrounding the largest realgar mine in Asia, and to lay a good foundation for further necessary pollution control actions and decisions. Methods A field survey was conducted to collect soil samples according to the Technical rules for monitoring of environmental quality of farmland soil (NY/T 395-2012), and then inductively coupled plasma mass spectrometry was used to determine the contents of 28 heavy metals [cadmium (Cd), arsenic (As), lead (Pb), mercury (Hg), chromium (Cr), nickel (Ni), copper (Cu), zinc (Zn), beryllium (Be), selenium (Se), cobalt (Co), antimony (Sb), molybdenum (Mo), vanadium (V), barium (Ba), thallium (Tl), boron (B) , bismuth (Bi), lithium (Li), manganese (Mn), strontium (Sr), calcium (Ca), rubidium (Rb), iron (Fe), magnesium (Mg), aluminum (Al), kalium (K), and titanium (Ti)]. Geoaccumulation index, single factor pollution index, and Nemerow comprehensive index were used to evaluate the degree and characteristics of single metal pollution and combined pollution in soil, respectively. A health risk assessment model was used to evaluate the risks of metals in soil to human health. Results The results of geoaccumulation index calculation revealed that 22 heavy metals were enriched in the soil, and the indexes of target heavy metals from high to low were Cd > Se > Pb >Hg > As > Co> Ni > Cu > Zn > Bi > Sb > Mo > Be> Cr > Ba >V > Li > Sr> Mn> Rb > Ca> Tl . The single factor pollution indexes of 17 heavy metals from high to low were Be > Cd > B > Mo > V > As > Ni > Cu > Pb > Zn > Co > Se > Tl > Ba > Cr > Hg > Sb. The Nemerow comprehensive index indicated all sampling points were graded as severe pollution. The mean of total non-carcinogenic health risk values and the mean of carcinogenic health risk values for the target heavy metals in the area were higher than the threshold (1) and the maximum acceptable risk (1.0×10^–4), respectively. The total carcinogenic health risks for adults and children reached 1.1×10^–3 and 1.67×10^–3, respectively. The mean non-carcinogenic health risk values of As, Co, Cr, and Pb pollution were greater than 1, and the maximum non-cancer risk value of Sb for children was greater than 1. The mean carcinogenic risk values of Ni, As, and Cu exceeded 1.0×10^–4 for both adults and children, and the maximum carcinogenic risk values of Be and Cr for children were more than 1.0×10^–4. Conclusion The farmland soil around the hugest realgar mine in Asia is contaminated by multiple metals. The study soil is seriously polluted by Cd, Se, Pb, As, Hg, Be, B, Mo, V, Ni, Cu, Pb, Zn, Co, and Ba. The pollution of Ni, As, Cu, Cr, and Be is considered as carcinogenic hazards to health, while the pollution of As, Co, Cr, Pb, and Sb poses non-carcinogenic health risks. Our study findings show that the soil is polluted by Co and Group 1 carcinogen Be, which could cause health risks; although Cr and Sb have not reached severe pollution levels, there are certain health risks and also need attention.

Objective To investigate the effect of transplantation of bone marrow mesenchymal stem cells (MSCs) in subarachnoid space on chronic neuropathic pain in rats. Methods One hundred and forty female SD rats weighing 180-200 g were used in this study. Chronic neuropathic pain (NP) was induced by ligation and separation of tibial and common fibular nerves (SNI). Two weeks after the surgery the animals were randomly divided into4 groups (n=35 each):group Ⅰ NP; group Ⅱ NP+ MSC (MSCs); group Ⅲ NP+ phosphate buffer saline (PBS) and group Ⅳ NP+ bone marrow monocyte (BNMCs). MSCs 10 μl, PBS 10 μl and BNMCs 10 μl were injected into subaraclmoid space at 2 weeks after surgery in group Ⅱ , Ⅲ and Ⅳ respectively. Paw withdrawal threshold to yon Frey filament stimulation (PWT) was measured before surgery (T0, baseline), at 2 weeks after surgery (T1) and 1, 2, 3, 4 and 5 weeks after subarachnoid injection (T2-6). Five animals were killed at T1-6 in each group and their lumbar enlargements were removed for determination of BDNF mRNA expression. Results PWT was significantly decreased by SNI at T1 in all 4 groups, and at T2-6 in group Ⅰ , Ⅲ and Ⅳ as compared with the baseline at T0 (P ＜ 0.05). Subarachnoid MSC transplantation significantly reduced mechanical hyperalgesia at T2-6 and up-regulated BDNF mRNA expression at T2-4 as compared with that at T1 (P ＜0.05). There was no significant change in PWT and BDNF mRNA expression after subarachnoid PBS and BNMCs injection in group Ⅲ and Ⅳ (P ＞ 0.05). Compared with group Ⅰ , PWT was significantly increased and BDNF mRNA expression was up-regulated in group Ⅱ (P ＜ 0.05), but no significant change in PBS and BNMCs was found in group Ⅲ (P ＞ 0.05) .Conclusion Up-regulation of BDNF mRNA expression in the spinal cord may be involved in the amelioration of chronic neuropathic pain by subarachnoid bone marrow mesenchymal stem cell transplantation.

OBJECTIVETo develop an HPLC method to determine Puerarin, Daidzin and Daidzein in Pueraria lobata.

METHODThe separation was performed in a SYMMETRY C18 column with a mobile phase of methanol-1% HAC solution (gradient elution), the The detection wavelength being 250 nm.

RESULTThe average recovery was respectively 101.7%, 100.7% and 101.7% (n = 3), RSD 0.43%, 0.82% and 1.50% (n = 3) for Puerarin, Daidzin and Daidzein.

CONCLUSIONThis method is suitable for the determination of Puerarin, Daidzin and Daidzein in Pueraria lobata and its preparation.

China ; Chromatography, High Pressure Liquid ; methods ; Ecosystem ; Isoflavones ; analysis ; Plant Roots ; chemistry ; Plants, Medicinal ; chemistry ; Pueraria ; chemistry ; Quality Control