Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Background::Limited information exists regarding the impact of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection on psoriasis patients. The objective of this study was to identify clinical factors associated with the prognosis of psoriasis following SARS-CoV-2 infection.Methods::A retrospective, multicenter study was conducted between March and May 2023. Univariable and multivariable logistic regression analyses were employed to identify factors associated with coronavirus disease 2019 (COVID-19)-related psoriasis outcomes. The study included 2371 psoriasis patients from 12 clinical centers, with 2049 of them having been infected with SARS-CoV-2.Results::Among the infected groups, lower exacerbation rates were observed in individuals treated with biologics compared to those receiving traditional systemic or nonsystemic treatments (22.3% [236/1058] vs. 39.8% [92/231] vs. 37.5% [140/373], P <0.001). Psoriasis progression with lesions (adjusted odds ratio [OR] = 8.197, 95% confidence interval [95% CI] = 5.685–11.820, compared to no lesions), hypertension (adjusted OR = 1.582, 95% CI = 1.068–2.343), traditional systemic (adjusted OR = 1.887, 95% CI= 1.263–2.818), and nonsystemic treatment (adjusted OR= 1.602, 95% CI= 1.117–2.297) were found to be associated with exacerbation of psoriasis after SARS-CoV-2 infection, but not biologics (adjusted OR = 0.931, 95% CI = 0.680–1.274, compared to no treatment), according to multivariable logistic regression analysis. Conclusions::A reduced risk of psoriasis exacerbation after SARS-CoV-2 infection was observed with biologics compared to traditional systemic and nonsystemic treatments. Significant risk factors for exacerbation after infection were identified as existing psoriatic lesions and hypertension.

Objective To compare the clinical efficacies of unilateral biportal endoscopy(UBE)technique and percutaneous endoscopic lumbar discectomy(PELD)technique in the treatment of lumbar disc herniation.Methods The clinical data of 149 patients with lumbar disc herniation in our hospital were retrospectively analyzed and divided into the UBE group(n=80)and the PELD group(n=69)according to different surgical methods.The operation time,intraoperative fluoroscopy frequency,intraoperative blood loss,hospital stay,postoperative complications,visual analogue scale(VAS)score,Oswestry disability index(ODI)score,intervertebral disc height and vertebral canal area of the two groups were compared.Results The operation time in the UBE group was longer than that in the PELD group,and the intraoperative fluoroscopy frequency was fewer than that in the PELD group,the differences were statistically significant(P<0.001).There was no significant difference in the intraoperative blood loss or hospital stay between the two groups(P>0.05).There was no significant difference in the VAS or ODI scores at each time point between the two groups(P>0.05).There was no significant difference in the intervertebral disc height or vertebral canal area at each time point between the two groups(P>0.05).The postoperative vertebral canal areas of patients in the two groups were greater than those before surgery,and the differences were statistically significant(P<0.05).The incidence of postoperative complications in the UBE group was lower than that in the PELD group,the difference was statistically significant(P<0.05).Conclusion In terms of short-term efficacy,both PELD technique and UBE technique can effectively relieve the symptoms of low back and leg pain caused by lumbar disc herniation,and the UBE technique has longer operation time,but with fewer intraoperative fluoroscopy frequency,and lower incidence of postoperative complications.

Objective:To investigate the clinical significance of bone metabolic indexes for disease assessment and curative effect monitoring in multiple myeloma(MM)bone disease(MBD)patients with different blood separation results.Methods:A total of 134 newly diagnosed MM patients treated in Cangzhou Hospital of Integrated TCM-WM-Hebei were enrolled and divided into control group[119 cases,serum,colloid and red blood cell(RBC)from top to bottom of sample]and abnormal group(15 cases,serum,mixed layer of RBC and serum,colloid and RBC from top to bottom of sample)according to the results of blood separation.According to the imaging findings,MBD was classified into grade 0-4,grade 0-2 was mild,and grade 3-4 was severe.The MBD grade of patients in the two groups was analyzed.The curative effect of MBD patients after chemotherapy and the changes of blood separation results and bone metabolic indexes before and after treatment were evaluated.The correlation between β 2-microglobulin(MG)and bone metabolic indexes was analyzed by Pearson correlation analysis.Results:In the control group,there were 69 cases of grade 0-2 and 50 cases of grade 3-4,while in the abnormal group,there were 5 cases of grade 0-2 and 10 cases of grade 3-4,the difference was statistically significant(P＜0.05).The serum β 2-MG,β-CTX levels in abnormal group were both significantly higher than those in control group,while the levels of P1NP and osteocalcin(OC)were significantly lower(all P＜0.001).In the control group,there were 95 patients with ≥ partial response(PR)and the blood separation results were not changed,while 24 patients with＜PR and 5 of them had abnormal blood separation results.In the abnormal group,9 patients with efficacy≥PR showed normal blood separation results,while 6 patients with efficacy＜PR and 5 of them still remained abnormal blood separation results.Compared with before treatment,β-CTX and β 2-MG of patients with efficacy ≥ PR were significantly decreased but P1NP and OC increased in the control group(all P＜0.00 1),which was the same as abnoraml group(both P＜0.001,P＜0.01).There were no significant changes in the levels of all indexes in the two groups of patients with efficacy＜PR(P＞0.05).Compared with before treatment,the levels of β-CTX and β 2-MG in the control group with unchanged blood separation results were significantly decreased(both P＜0.00l),while the levels of P1NP and OC were significantly increased(P＜0.01,P＜0.001),and the level of each index in the patients transformed to abnormal blood separation result after treatment did not significantly change(P＞0.05);the levels of β-CTX and β 2-MG in the abnormal group transformed to normal blood separation result were significantly decreased(both P＜0.01),while the levels of P1NP and OC were significantly increased(P＜0.001,P＜0.01),and the level of each index in patients with unchanged blood separation results did not significantly change(P＞0.05).Pearson correlation analysis showed that serumβ 2-MG was positively correlated with β-CTX(r=0.709,P＜0.001),and negatively correlated with P1NP and OC(r=-0.410,r=-0.412,both P＜0.001).Conclusion:MBD patients with abnormal blood separation results have higher bone disease grade and poor prognosis,which is closely related to the significant increase of bone resorption index β-CTX level and decrease of bone formation index P1NP and OC levels,leading to more serious bone metabolic homeostasis disorder.The results of blood separation combined with the changes of bone metabolic indexes can be used as one of the comprehensive predictors of disease condition,efficacy monitoring and prognosis evaluation of MBD patients.

Objective:To explore the protective effect and mechanism of acetate on sepsis-induced acute kidney injury (AKI) in rats.Methods:Male Sprague-Dawley (SD) rats were divided into sham operation group (Sham group), sepsis group caused by cecal ligation and puncture (CLP group), and acetate pretreatment group [NaA group, gavage sodium acetate (NaA) 300 mg/kg twice a day for 7 consecutive days before CLP] using a random number table method, with 7 rats in each group. The blood was taken from the main abdominal artery 24 hours after modeling, and renal tissue was collected from the rats. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α), and kidney injury molecule-1 (KIM-1). The concentration of serum acetate was determined by high performance liquid chromatography. The level of malondialdehyde (MDA) in renal tissue was detected by thiobarbituric acid method. Myeloperoxidase (MPO) in renal tissue was detected by colorimetric method. Hematoxylin-eosin (HE) staining was used to observe histopathological changes and assess renal tubule injury score. Western blotting was used to detect the protein expressions of G-protein coupled receptor 43 (GPR43) and adenosine monophosphate-activated protein kinase/silence infor-mation regulator 1/peroxlsome proliferator-activated receptor-γ coactlvator-1α (AMPK/SIRT1/PGC-1α) pathway. The positive expressions of GPR43, phosphorylation-AMPK (p-AMPK), SIRT1, PGC-1α were detected by immunohistochemistry.Results:Compared with Sham group, the serum levels of IL-6, TNF-α and KIM-1 were significantly increased in CLP group, the contents of MDA and MPO in renal tissue were increased, and the content of acetate was significantly decreased. HE staining results showed that most of the tubular epithelial cells were denaturated with local necrosis, a large number of brush border injuries and shedding, tubular structure destruction and fragmentation, and more inflammatory cells infiltrated the renal interstitium, the renal tubular injury score significantly increased. The expressions of GPR43, p-AMPK/AMPK, SIRT1, and PGC-1α in renal tissue were significantly reduced, indicating renal injury and increased levels of oxidative stress and inflammation in septic rats. Compared with the CLP group, the serum levels of IL-6, TNF-α and KIM-1 in the NaA group were decreased [IL-6 (ng/L): 126.20±6.23 vs. 161.00±17.37, TNF-α (ng/L): 85.59±7.70 vs. 123.50±17.78, KIM-1 (μg/L): 2.92±0.38 vs. 4.73±0.36, all P < 0.05]. The contents of MDA and MPO in renal tissue were significantly decreased [MDA (μmol/g): 6.56±0.18 vs. 8.53±0.34, MPO (U/g): 2.99±0.20 vs. 3.72±0.29, both P < 0.05]. HE staining showed that kidney injury had been alleviated, with a decrease in renal tubular injury score [1 (1, 2) vs. 3 (2, 3), P < 0.05]. Western blotting showed that the expressions of GPR43 and AMPK/SIRT1/PGC-1α pathway related proteins were significantly increased in renal tissue (GPR43/β-actin: 0.62±0.09 vs. 0.41±0.09, p-AMPK/AMPK: 0.58±0.07 vs. 0.44±0.06, SIRT1/β-actin: 0.85±0.06 vs. 0.73±0.03, PGC-1α/β-actin: 0.79±0.07 vs. 0.62±0.05, all P < 0.05). Immunohistochemistry showed that the positive expressions of GPR43, p-AMPK, SIRT1 and PGC-1α were significantly increased in renal tissue [GPR43 positive area: (33.66±2.62)% vs. (16.21±1.66)%, p-AMPK positive area: (16.64±2.11)% vs. (5.04±1.28)%, SIRT1 positive area: (14.61±2.86)% vs. (7.34±1.00)%, PGC-1α positive area: (15.30±2.39)% vs. (4.84±1.67)%, all P < 0.05], the serum acetate concentration significantly increased (μg/L: 32?479±14?683 vs. 12?935±3?197, P < 0.05). Conclusion:Acetate can ameliorate sepsis-induced AKI, the mechanism may be related to the activation of AMPK/SIRT1/PGC-1α pathway by GPR43.

Objective:To investigate the effects of PD-1 monoclonal antibody therapy on the peripheral and local immune microenvironment of patients with microsatellite instability-high(MSI-H)rectal cancer.Methods:Samples of peripheral blood and tumor biopsy were collected from a patient with MSI-H rectal cancer before and after PD-1 monoclonal antibody treatment.The samples were dissociated into single-cell suspensions using a combination of enzymatic and mechanical methods.Immune-related marker expression on peripheral and tumor-infiltrating im-mune cells was analyzed using single-cell mass cytometry(CyTOF).Results:According to the results of CyTOF analysis,CD45+immune cells in the peripheral blood and tumor tissues were categorized into 39 and 34 cell subsets,respectively,before and after PD-1 monoclonal antibody treatment(the correlation is unclear and ambiguous).After PD-1 monoclonal antibody treatment,differences were observed in the relative abundance of immune cell subsets:B cells significantly decreased in the peripheral blood,while B cells and γδT cells significantly increased in the tumor tissue;neutrophils significantly decreased,and the proportion of CD4+TEM cells in T cell subsets significantly increased,whereas CD4+Treg cells significantly decreased.Additionally,there were differences in the expression of immune-related markers in multiple immune cell subsets in both peripheral blood and tumor tissues,with CCR6 showing a significant increase in expression across all subsets,while ICOS and PD-1 expressions in T cell subsets were significantly reduced(the specific tissues for these cells or factors are unclear).Conclusion:After PD-1 monoclonal antibody treatment in MSI-H rectal cancer,changes occurred in the composition of immune cells and the expression of immune-related markers in both peripheral blood and tumor tissues.This study reveals the dynamic adjustment of the immune microenvironment and provides important evidence for understanding the therapeutic mechanism of PD-1 monoclonal antibodies.

Objective:To investigate the effects of Xiongcan Yishen Formula(XYF)on ferroptosis in mouse TM3 Leydig cells after oxidative stress injury(OSI)induced by H2O2.Methods:An oxidative stress injury model was established in mouse TM3 Leydig cells using H2O2 induction.The modeled TM3 cells were randomly divided into OSI group,XYF group,the ferroptosis inhibitor Ferrostatin-1(F-1)group,and F-1+XYF group,which were respectively intervened with blank serum,20%drug-containing serum,2μmol/L F-1,and2μmol/L F-1+20%drug-containing serum.A control group(normal TM3 cells+blank serum)was also set up.The morphology of cells in each group was observed,and the levels of testosterone,superoxide dismutase(SOD),reactive oxygen spe-cies(ROS),malondialdehyde(MDA),ferritin heavy chain 1(FTH1),solute carrier family 7 member 11(SLC7A11),glutathione(GSH),glutathione peroxidase 4(GPX4),fatty acid CoA ligase 4(FACL4),total iron ions,and ferrous ions were detected.Re-sults:Compared with the model group,the control group showed significantly decreased expression of ROS,MDA,FACL4,total iron,and ferrous ions(P<0.05),and significantly increased levels of testosterone,SOD,GSH,FTH1,SLC7A11,and GPX4(P<0.05).The male silkworm kidney-tonifying formula group significantly promoted testosterone secretion by TM3 cells and upregulated the expression of FTH1,SLC7A11,GPX4,GSH,and SOD in TM3 cells(P<0.05),while significantly downregulating ROS,MDA,FACL4,total iron ions,and ferrous ions(P<0.05).Conclusion:Following H2O2 exposure,oxidative stress can induce ferroptosis in mouse TM3 Leydig cells.XYF can antagonize OSI and ferroptosis in TM3 cells by activating the SLC7A11/GSH/GPX4 axis,which may underlie the mechanism of XYF in the treatment of male late-onset hypogonadism.

AIM To analyze the constituents absorbed into blood and brain from Zhishe Tongluo Capsules.METHODS Sixteen rats were randomly assigned into four groups and given intragastric administration(3.1 g/kg),after which the cerebral ischemia-reperfusion injury(MACO)model was established,the blood and brain tissues were collected,and UHPLC-Q Exactive Focus MS/MS was adopted in the identification of prototype constituents.RESULTS Total 70 constituents were identified,20 of which were found in the blood,mainly including flavonoids,tanshinones and Ligusticum chuanxiong phthalides,and 7 of them could enter the brain through blood-brain barrier.Compared with the normal administration group,the MACO administration group demonstrated added constituents absorbed into blood containing 3-hydroxybenzoic acid,calycosin-7-glucoside,curcumenol,senkyunolide B,dihydrotanshinone I and cryptotanshinone;removed constituents absorbed into brain containing puerarin,elemicin,sedanolide,and added those containing salvianolic acid A,senkyunolide I,dihydrotanshinone I in the left brain tissues(infarcted side).CONCLUSION The constituents absorbed into blood and brain from Zhishe Tongluo Capsules,along with the enhanced absorptions of phthalides,quinones and phenols in MACO rats in vivo may be the active substances for treating cerebral infarction.

Objective:To explore the clinical effects of free anterolateral thigh perforator flap (ALTPF) with modified cross-leg vessel bridging in reconstruction of infected wounds in the lower leg combined with major vessel defects.Methods:A retrospective observational study was conducted on 7 patients who admitted to the Department of Trauma Orthopaedics, the 521 Hospital of Norinco Group from January 2020 to December 2021 for treatment of large infected wounds in lower leg with soft tissue defect by reconstructive surgery of flap transfer. The patients were 5 males and 2 females, aged 23-50 years old with an average age of 37 years old. The causes of injury were: 5 patients were of car accidents, 1 of machinery compression and 1 of heavy object crush. The wounds were reconstructed after debridement and infection control with sensitive antibiotics, where the soft tissue defects were found at 11.0 cm×15.0 cm to 20.0 cm×32.0 cm in size. All patients underwent vascular angiography or CDU examinations and it was confirmed that the affected calf had only an anterior tibial artery as the vessel left for blood supply in 6 patients and a posterior tibial artery as the blood supply vessel in one patient. Therefore application of vascular end-to-side anastomosis in free flap reconstruction of limb defects was impossible due to the damaged artery could not be salvaged as a blood supply artery for the transferred flap. Therefore, a modified cross-leg vessel bridging to the freed ALTPF in the affected lower leg was applied. The donor site of the pedicle was covered with VSD while the pedicle of the flap was anastomosed. It was remained until the posterior tibial artery and the tubular flap were ready for replantation after disconnection of the pedicle. The sizes of flap were 13.0 cm×17.0 cm to 22.0 cm×32.0 cm (unilateral ALTPFs for 6 patients and bilateral ALTPFs for 1 patient). Two donor sites in low tension were direct closed, and the rest of 5 donor sites that had great tensions and could not be directly sutured were reconstructed by skin grafting. The survival and complications of flaps were observed in the scheduled postoperative follow-ups at outpatient visits, WeChat reviews and home visits, etc.Results:All 7 patients were successfully treated and had 12-24 months postoperative follow-up, with an average of 16 months. All flaps survived, with primary healing in 6 patients and 1 patient had partial flap necrosis with surface infection, which healed after dressing changes. The wound healing time was 14-36 days with an average of 17.9 days. The time for disconnection of the cross-leg vessel bridging pedicle was 3-4 weeks with the flap transfer, with an average of 3.6 weeks. The donor sites of ALTPFs and vessel pedicles all healed well. CDU confirmed the patency of the contralateral posterior tibial artery. Satisfactory functional recovery was achieved in the affected lower limb and there was a good function of the contralateral healthy lower leg.Conclusion:Application of the transfer of a free ALTPF with modified cross-leg vessel bridging in reconstruction of infected wounds with major vessel defects in the lower leg has shown excellent clinical outcomes. It is a practical and effective method in treatment of large infective defect in lower leg.

In order to improve the level of refined management of medical consumables, a hospital used radio frequency identification (RFID) technology to map the unique device identification barcode of medical devices to the supply-processing-distribution (SPD) code, generating a medical consumables RFID tag code with dual code carrier function and a unique serial number. The " three streams in one" mutual integration management mode of hospital information flow, material flow and financial flow was constructed, which realized the whole lifecycle traceability of medical consumables, effectively improved the intelligence and accuracy of inventory control, further optimized the integration function of medical consumables industry and finance, and provided strong data support for the decision-making analysis of hospital operation and management.