ObjectiveTo investigate the potential machanism of Xiaozhong Zhitong Mixture （消肿止痛合剂， XZM） in the treatment of diabetes foot ulcer （DFU）. MethodsFifty SD rats were randomly divided into blank group， model group， XZM group， inhibitor group， XZM plus inhibitor group （combination group）， with 10 rats in each group. Except for the blank group， rats were fed with high-sugar， high-fat， high-cholesterol diet， intraperitoneally injected with streptozotocin， and subjected to skin defect to establish DFU model. After successful modeling， the XZM group and the combination group were given 1 ml/（100 g·d）of XZM by gavage， while the blank group， model group， and inhibitor group were all given an equal volume of 0.9% sodium chloride injection by gavage. Thirty minutes later， the inhibitor group and the combination group were intraperitoneally injected with 5 mg/（kg·d） of Notch1 inhibitor DAPT. All groups were treated once a day. After 14 days of administration， the skin tissue from the dorsal foot of the blank group rats and wound tissue from the other groups were collected. The pathological changes of granulation tissue in the wound were detected using hematoxylin eosin （HE） staining. The microvascular density （MVD） in wounds was detected through immunohistochemical staining. Real time fluorescence quantitative polymerase chain reaction （RT-PCR） and western blotting were used to detect the mRNA and protein levels of Notch1 homolog （Notch1）， Delta-like ligand 4 （Dll4）， Delta-like ligand 4 （VEGF）， and angiopoietin 2 （Ang-2）， respectively. ResultsHistological results showed that the epidermal structure in the dorsal foot skin tissue of the rats in the blank group was intact. In the wound tissue of the model group， the epidermis exhibited excessive keratinization， vacuolar cytoplasm， and a large number of inflammatory cells infiltrating the tissue， while in the XZM group， a large amount of scab formation was observed in the epidermis， with no significant inflammatory cell infiltration and a noticeable increase in fibroblasts. In the combination group and the inhibitor group， partial epidermal scab formation was observed in the wound tissue with a small amount of inflammatory cell infiltration. Compared to those in the blank group， the MVD in the wound tissue increased in the model group， as well as the mRNA expression and protein levels of Notch1 and Dll4， while VEGFA and Ang-2 mRNA expression and protein levels significantly decreased （P＜0.05 or P＜0.01）. Compared to those in the model group， the MVD in the wound tissue of all medication groups significantly increased， and the mRNA and protein levels of Notch1 and Dll4 decreased， while VEGFA and Ang-2 mRNA expression and protein levels increased （P＜0.05 or P＜0.01）. Compared to the XZM group， the inhibitor group and the combination group showed decreased MVD in wound tissue， increased Notch1 and Dll4 mRNA and protein levels， and decreased expression of VEGFA and Ang-2 mRNA and proteins （P＜0.05 or P＜0.01）. ConclusionXZM can effectively promote wound healing in DFU rats， and its mechanism of action may be related to the inhibition of Dll4/Notch1 signaling pathway in the wound tissue， therey promoting angiogenesis.

Objective To investigate the characteristics of changes in hepatitis B surface antigen(HBsAg),hepatitis B virus(HBV)deoxyribonucleic acid(DNA),and alanine aminotransferase(ALT)levels following the cessation of nucleos(t)ide analogues(NAs)therapy in hepatitis B e antigen(HBeAg)-negative chronic hepatitis B(CHB)patients with baseline HBsAg levels<1000 IU/ml.Methods This retrospective cohort study analyzed 73 HBeAg-negative CHB patients treated at the Fifth Medical Centre of Chinese PLA General Hospital from January 2020 to June 2023.Patients were divided into 3 groups according to baseline HBsAg level and discontinuation strategy:HBsAg-negative discontinuation group(n=14),HBsAg-positive discontinuation group(n=25),and HBsAg-positive continuation group(n=34).All patients were followed for 48 weeks.Baseline clinical characteristics and changes in virological and hepatic biochemical indicators during follow-up were compared among the 3 groups.Univariate logistic regression analysis was performed to assess the correlation between clinical indicators and HBV DNA reappearance in HBsAg-positive discontinuation group,and between clinical indicators and HBsAg decline>0.5 log IU/ml in this group.Results There were no significant differences in the baseline levels of gender,age,albumin,and total bilirubin among the 3 groups(P>0.05).The baseline direct bilirubin level was significantly higher in HBsAg-positive discontinuation group than that in other groups(P<0.05),while the lymphocyte counts were significantly higher in HBsAg-negative discontinuation group(P<0.05).During the 48-week follow-up period,the HBV DNA reappearance rate in HBsAg-positive discontinuation group(72.0%)was significantly higher than that in other groups(P<0.001).There was no significant difference in the incidence of ALT elevation among the three groups(P=0.260).The proportion of patients with HBsAg decline>0.5 log IU/ml in HBsAg-positive discontinuation group(24.0%)was significantly higher than that in HBsAg-positive continuation group(5.9%,P<0.05).The proportion of patients with HBsAg increase>0.5 log IU/ml in HBsAg-positive discontinuation group(12.0%)was also significantly higher than that in HBsAg-positive continuation group(0%,P<0.05).Univariate logistic regression analysis revealed no significant association between the analyzed clinical indicators and HBsAg decline(P>0.05).Conclusions Discontinuation of NAs therapy in HBsAg-negative patients demonstrates high safety,with sustained HBsAg negativity post-cessation and low risks of viral relapse and liver function abnormalities.For HBsAg-positive patients,discontinuation may promote HBsAg decline in some individuals but is associated with risks of HBV DNA reappearance and HBsAg elevation.The decision to discontinue therapy should be comprehensively evaluated based on patients'baseline HBsAg levels and clinical characteristics.

Objective:To compare the efficacy of posteromedial combined with lateral Frosch approach versus anterior medial and lateral dual incision approach in open reduction and internal fixation for Schatzker type VI tibial plateau fractures.Methods:A retrospective cohort study was conducted to analyze the clinical data of 41 patients with Schatzker type VI tibial plateau fractures, who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2018 to May 2024, including 23 males and 18 females, aged 34-79 years [(50.7±7.7)years]. Twenty-three patients underwent open reduction and internal fixation via the posteromedial combined with lateral Frosch approach (posterior approach group), while 18 patients underwent the same procedure via the anterior medial and lateral dual incision approach (anterior approach group). The following parameters were compared between the two groups: operation duration, intraoperative blood loss, postoperative drainage volume, depth of articular surface depression and tibial plateau width measured preoperatively, at 7 days, 3 months postoperatively, and at the last follow-up, medial proximal tibial angle (MPTA) and posterior proximal tibial angle (PPTA) measured at 7 days, 3 months postoperatively, and at the last follow-up, visual analogue scale (VAS) scores assessed preoperatively, at 7 days postoperatively, and at the last follow-up, American Knee Society (KSS) score and knee flexion range of motion assessed at 7 days, 3 months postoperatively, and at the last follow-up, fracture healing status at the last follow-up, and incidence of postoperative complications.Results:All the patients were followed up for 12-16 months [(14.3±2.1)months]. The operation duration was (119.6±11.8)minutes in the posterior approach group, which was significantly shorter than (140.3±10.6)minutes in the anterior approach group ( P<0.05). There were no statistically significant differences in intraoperative blood loss or postoperative drainage volume between the two groups ( P>0.05). No significant differences were found in the preoperative depth of articular surface depression or tibial plateau width between the two groups ( P>0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the depth of articular surface depression was 0.8(0.6, 1.0)mm, 0.6(0.5, 0.8)mm, and 0.6(0.5, 0.7)mm in the posterior approach group, which were significantly shorter than 1.1(0.9, 1.3)mm, 0.8(0.7, 1.0)mm, and 0.8(0.7, 1.0)mm in the anterior approach group ( P<0.05). The tibial plateau width at the same time points was 71.0(69.1, 73.5)mm, 70.5(69.2, 72.9)mm, and 70.5(69.3, 72.5)mm in the posterior approach group, which were significantly shorter than 73.0(72.3, 74.2)mm, 71.5(71.0, 73.0)mm, and 71.5(71.1, 72.6)mm in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the MPTA values were (87.4±0.7)°, (87.7±0.6)°, and (87.9±0.5)° in the posterior approach group, which were significantly larger than (85.2±2.5)°, (86.0±2.2)°, and (86.3±2.0)° in the anterior approach group ( P<0.01). The PPTA values at the same time points were (9.5±0.7)°, (9.0±0.5)°, and (8.6±0.4)° in the posterior approach group, which were significantly smaller than (11.2±1.0)°, (10.3±0.8)°, and (9.8±0.7)° in the anterior approach group ( P<0.01). There was no significant difference in the preoperative VAS score between the two groups ( P>0.05). At 7 days postoperatively and at the last follow-up, the VAS scores were 4.0(3.0, 5.0)points and 0.5(0.0, 2.0)points in the posterior approach group, which were significantly lower than 5.0(4.0, 5.0)points and 1.0(1.0, 3.0)points in the anterior approach group ( P<0.05). At 7 days, 3 months postoperatively, and at the last follow-up, the KSS scores were 62.5(57.0, 67.5)points, 75.5(72.0, 82.5)points, and 87.0(82.5, 93.5)points in the posterior approach group, which were significantly higher than 61.5(54.5, 63.0)points, 74.0(68.0, 79.0)points, and 85.5(78.0, 88.5)points in the anterior approach group ( P<0.05). The knee flexion range of motion was 90.0(85.0, 95.0)°, 115.0(109.0, 122.0)°, and 126.0(120.0, 130.0)° in the posterior approach group, which were significantly greater than 80.5(75.2, 85.8)°, 110.0(104.0, 115.0)°, and 119.0(113.0, 122.0)° in the anterior approach group ( P<0.05). At the last follow-up, all the fractures were healed in both groups. No statistically significant difference was found in the incidence of postoperative complications between the two groups ( P>0.05). Conclusion:Compared to the anterior medial and lateral dual incision approach, the posteromedial combined with lateral Frosch approach demonstrates superior advantages in operation duration, reduction quality, pain relief, functional recovery in the treatment of Schatzker type VI tibial plateau fractures, while the incidence of complications is comparable.

Objective:To investigate the efficacy of cementless long-stem total hip arthroplasty (THA) in the treatment of end-stage osteonecrosis of the femoral head (ONFH) combined with ipsilateral subtrochanteric femoral fractures.Methods:A retrospective case series study was conducted on 18 patients with end-stage ONFH combined with ipsilateral subtrochanteric fractures who were admitted to the 940th Hospital of the Joint Logistics Support Force of the PLA from January 2016 to June 2023, including 8 males (8 hips) and 10 females (10 hips), aged 56-79 years [(69.4±7.0)years]. All the patients had Association Research Circulation Osseous (ARCO) stage IV ONFH combined with ipsilateral subtrochanteric fracture (Seinsheimer types II-IV). Parameters recorded included operation duration, intraoperative blood loss, length of hospital stay, time to partial weight-bearing, and time to full weight-bearing. Vertical offset and leg length discrepancy (LLD) were compared preoperatively and at 1 week postoperatively. Visual analogue scale (VAS) score, hip range of motion (flexion, abduction), and Harris hip score (HHS) were compared preoperatively, at 1 week, 3 months postoperatively, and at the last follow-up. Perioperative complications were observed.Results:All the patients were followed up for 12-70 months [(36.4±16.2)months]. Operation duration was (116.4±18.1)minutes. Intraoperative blood loss was (334.4±121.3)ml. The length of hospital stay was 13.0(10.0, 16.3)days. The time to partial weight-bearing was 5.0(3.0, 7.0)days, with time to full weight-bearing for 5.0(4.0, 5.3)weeks. At 1 week postoperatively, the vertical offset [(58.9±4.1)mm] was significantly increased compared to that preoperatively [(49.3±3.3)mm] ( P<0.01), while the LLD [(4.2±3.1)mm] was significantly reduced compared to that preoperatively [(16.2±5.8)mm] ( P<0.01). At 1 week, 3 months postoperatively and at the last follow-up, the VAS scores [3.0(2.0, 3.3)points, 2.0(1.0, 2.0)points, and 1.0(0.0, 2.0)points] were significantly lower than that preoperatively [6.0(5.0, 6.3)points], and decreased with the passage of follow-up time ( P<0.01); the hip flexion angles [(50.4±6.5)°, (94.3±6.4)°, and (104.7±7.4)°] and hip abduction angles [(21.5±4.4)°, (34.9±4.5)°, and (42.9±4.9)°] were lower than those preoperatively [(32.9±6.4)° and (13.4±4.9)°], and decreased with the passage of follow-up time ( P<0.01); the HHS [(58.1±4.9)points, (83.1±2.9)points, and (90.7±2.6)points] were higher than that preoperatively [(33.4±4.4)points], and increased with the passage of follow-up time ( P<0.01). At the last follow-up, 5 patients were rated as excellent, 11 as good, and 2 as fair according to the HHS criteria, with an overall excellent and good rate of 89%. No perioperative complications were observed, including neurovascular injury, secondary fracture, or infection. One patient developed partial deep vein thrombosis of the lower extremity (the popliteal vein) at 2 weeks after surgery, which recovered completely following treatment with a standard oral administration of rivaroxaban, etc. At the last follow-up, no evidence of malunion, prosthesis loosening, subsidence, or dislocation was observed. Conclusion:The use of cementless long-stem THA in the treatment of end-stage ONFH combined with ipsilateral subtrochanteric fractures has advantages of small trauma, early weight-bearing, early pain relief, improved joint motion and function, and few complications.

This study aims to explore the specific mechanism by which puerarin inhibits ferroptosis and improves the myocardial contractile function in myocardial hypertrophy through the nuclear factor erythroid 2-related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) signaling pathway. The hypertrophic cardiomyocyte model was established using phenylephrine, and H9c2 cells were divided into control group, model group, puerarin group, and puerarin+ML385 group. Cell viability and surface area were detected by cell counting kit-8(CCK-8) and immunofluorescence experiments. The mitochondrial membrane potential and Ca~(2+) concentration were measured. The ferroptosis-related indicators were detected by biochemical and fluorescence staining methods. The expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway was detected by Western blot. A myocardial hypertrophy model was established, and 40 rats were randomly divided into sham group, model group, puerarin group, and puerarin+Nrf2 inhibitor(ML385) group, with 10 rats in each group. Echocardiogram, hemodynamic parameters, and myocardial hypertrophy parameters were measured. Histopathological changes of myocardial tissues were observed by hematoxylin and eosin(HE) staining and Masson staining. Biochemical methods, enzyme-linked immunosorbent assay(ELISA), and fluorescence staining were used to detect inflammatory factors and ferroptosis-related indicators. Immunohistochemistry was used to detect the expression of proteins related to ferroptosis and the Nrf2/ARE/HO-1 signaling pathway. Cell experiments showed that puerarin intervention significantly enhanced the viability of hypertrophic cardiomyocytes, reduced their surface area, and restored mitochondrial membrane potential and Ca~(2+) homeostasis. Mechanism studies revealed that puerarin promoted Nrf2 nuclear translocation, upregulated the expression of HO-1, solute carrier family 7 member 11(SLC7A11), and glutathione peroxidase 4(GPX4), and decreased malondialdehyde(MDA), reactive oxygen species(ROS), and iron levels. These protective effects were reversed by ML385. In animal experiments, puerarin improved cardiac function in rats with myocardial hypertrophy, alleviated myocardial hypertrophy and fibrosis, inhibited inflammatory responses and ferroptosis, and promoted nuclear Nrf2 translocation and HO-1 expression. However, combined intervention with ML385 led to deterioration of hemodynamics and a rebound in ferroptosis marker levels. In conclusion, puerarin may inhibit cardiomyocyte ferroptosis through the Nrf2/ARE/HO-1 signaling pathway, thereby improving myocardial contractile function in myocardial hypertrophy.
Animals ; NF-E2-Related Factor 2/genetics* ; Rats ; Ferroptosis/drug effects* ; Signal Transduction/drug effects* ; Isoflavones/pharmacology* ; Male ; Rats, Sprague-Dawley ; Cardiomegaly/genetics* ; Myocytes, Cardiac/metabolism* ; Antioxidant Response Elements/drug effects* ; Myocardial Contraction/drug effects* ; Heme Oxygenase-1/genetics* ; Cell Line

OBJECTIVE: To compare the effectiveness of different puncture methods of the flexible bone cement delivery device in unilateral percutaneous curved vertebroplasty for osteoporotic vertebral upper 1/3 compression fractures. METHODS: A retrospective analysis was conducted on the clinical data of 67 patients with osteoporotic vertebral upper 1/3 compression fractures who were admitted and met the selection criteria between January 2023 and April 2024. The patients were divided into two groups based on the puncture method of the flexible bone cement delivery device: the oblique puncture group ( n=37) and the parallel puncture group ( n=30). There was no significant difference ( P>0.05) between the two groups in terms of gender, age, bone mineral density (T value), distribution of fractured vertebrae, time from injury to operation, and preoperative visual analogue scale (VAS) score for pain, Oswestry disability index (ODI), anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra. The following parameters were compared between the two groups: operation time, incidence of secondary puncture, incidence of bone cement leakage, volume of injected bone cement, bone cement distribution score, as well as VAS score, ODI, anterior vertebral height of the fractured vertebra, and Cobb angle of the fractured vertebra at 1 day after operation and at last follow-up. RESULTS: Two cases in the oblique puncture group and 7 cases in the parallel puncture group underwent secondary puncture during operation, and the difference in the incidence of secondary puncture was significant ( P<0.05). No complications such as bone cement hypersensitivity, bone cement embolism, nerve injury, or epidural hematoma occurred in both groups. There was no significant difference in operation time, volume of injected bone cement, incidence of bone cement leakage, distribution score and rating of bone cement between the two groups ( P>0.05). All patients were followed up 6-18 months (mean, 12.0 months), and there was no significant difference in the follow-up time between the two groups ( P>0.05). No further fracture collapse or compression occurred in the fractured vertebra during follow-up. Both groups exhibited significant improvements in VAS score, ODI, anterior vertebral height, and Cobb angle of the fractured vertebra after operation compared to baseline ( P<0.05). There were also significant differences between the two time points after operation ( P<0.05). However, there was no significant difference in the above indicators between the two groups ( P>0.05). CONCLUSION For osteoporotic vertebral upper 1/3 compression fractures treated with unilateral percutaneous curved vertebroplasty, both oblique and parallel puncture methods of the flexible bone cement delivery device can effectively relieve pain, but the former is more conducive to reducing the incidence of secondary puncture.
Humans ; Bone Cements/therapeutic use* ; Fractures, Compression/surgery* ; Retrospective Studies ; Vertebroplasty/instrumentation* ; Osteoporotic Fractures/surgery* ; Spinal Fractures/surgery* ; Female ; Male ; Aged ; Middle Aged ; Treatment Outcome ; Punctures/methods* ; Aged, 80 and over

Objective To explore the effect of PCSK9 inhibitor combined with atorvastatin on carotid atherosclerosis and its anti-inflammatory effect in patients with hypertension complicated with type 2 diabetes mellitus.Methods A total of 100 patients with hypertension complicated with type 2 diabetes mellitus who were treated in Nanchang Third Hospital from October 2022 to August 2023 were selected as the research subjects.They were divided into the control group and the study group by the random number table method,with 50 cases in each group.Both groups of patients received conventional antihypertensive,hypoglycemic,and antiplatelet therapy.The control group took 20 mg of atorvastatin calcium tablets orally,once a night.On the basis of the control group,the study group was additionally given 150 mg of evolocumab injection(a PCSK9 inhibitor)by subcutaneous injection,once every two weeks.Both groups of patients were followed up for 24 weeks.The levels of blood lipids,blood glucose,inflammatory cytokines,carotid intima-media thickness(IMT),atherosclerotic plaque score and adverse reactions of the patients in the two groups before and after treatment were detected and compared.Results The levels of TC,TG and LDL-C in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜0.05).The levels of IL-1,IL-6,TNF-α,hs-CRP,as well as the ca-rotid IMT and atherosclerotic plaque score in the study group after treatment were lower than those before treatment and those in the control group at the same period,and the differences were statistically significant(P＜O.05).During the treatment period,there was no significant difference in the occurrence of adverse reac-tions between the two groups(P＞0.05).Conclusion The combination of PCSK9 inhibitor and atorvastatin can effectively regulate the blood lipid levels of patients with hypertension complicated and type 2 diabetes mellitus,alleviate the inflammatory response,and improve the degree of carotid atherosclerosis in these pa-tients.

The traditional detection methods for monitoring the biomass,protein,chlorophyll content and other key indicators in the growth of chlorella have some problems,including complicated operation,slow detection speed and difficult large-scale application.In this study,a fast and efficient monitoring method for the key indicators in the growth of chlorella was established using near infrared spectroscopy and chemometrics.Near-infrared spectroscopy was used to collect near-infrared spectra of chlorella algal fluid at different growth stages,and standard methods were used to detect the biomass,protein and chlorophyll contents of corresponding samples.A quantitative analysis model was established based on partial least squares regression(PLSR).To improve the prediction ability of the model,multiplicative scatter correction(MSC)was used to reduce the interference of scattering on the raw spectrum(RS),standard normal variate(SNV)was used to normalize the original spectral data to eliminate differences between samples,continuous wavelet transform(CWT)was used to obtain the key features of spectral data,the first derivative(1st)was used to enhance the differentiation of the original spectral features,and monte carlo-uninformative variable elimination(MC-UVE)and randomization test(RT)were used to screen the valid variables in the wavelength.By evaluating the prediction ability of different models,the quantitative analysis models of chlorella biomass,protein and chlorophyll content were finally determined.The results showed that the model based on 1st combined with RT spectra had better predictive ability for chlorella nutrient content detection,and the root mean square errors of prediction(RMSEP)and coefficients of determination(R2)were 0.041 and 0.933 for biomass,0.012 and 0.973 for protein,and 0.517 and 0.962 for chlorophyll,respectively.This model showed practical application value,and could realize the rapid and accurate detection of chlorella biomass,protein and chlorophyll content at the same time.

[This corrects the article DOI: 10.1016/j.apsb.2022.05.019.].

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.