OBJECTIVE: To investigate the effects of using different filters in continuous renal replacement therapy (CRRT) on the mortality, inflammatory mediator level and hemodynamics in patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective study was conducted. The patients with SA-AKI undergoing first CRRT admitted to the critical care medicine department of General Hospital of Ningxia Medical University from August 2022 to October 2023 were enrolled as the study objects, and they were divided into observation group and control group by random number table method. All patients received routine treatment including anti-infection, optimized volume management and organ function support. On this basis, the observation group was treated with oXiris filter for CRRT, while the control group was treated with ordinary filter for CRRT, and the first treatment time was ≥ 36 hours. General data of the two groups were collected and compared. At the same time, the inflammatory indicators [high-sensitivity C-reactive protein (hs-CRP), procalcitonin (PCT), interleukin-6 (IL-6)], sequential organ failure assessment (SOFA) score, mean arterial pressure (MAP), blood lactic acid (Lac), noradrenaline dosage and other related indicators were collected before CRRT treatment and 24 hours and 48 hours after treatment, and the 7-day and 28-day mortality of patients were recorded. RESULTS: Finally, 65 patients were enrolled, including 30 in the observation group and 35 in the control group. There were no significant differences in baseline data including age, gender, acute kidney injury (AKI) stage and infection source between the two groups. The 7-day mortality of observation group was significantly lower than that of control group [16.7% (5/30) vs. 42.9% (15/35), P < 0.05]. There was no significant difference in 28-day mortality between the observation group and the control group [36.7% (11/30) vs. 54.3% (19/35), P > 0.05]. There were no significant differences in inflammation indicators, SOFA score, MAP, Lac and norepinephrine dosage before treatment between the two groups. After 24-hour and 48-hour treatment, the hemodynamics of the two groups were stable compared with before treatment, the inflammatory indicators, SOFA score, Lac and norepinephrine dosage were reduced to varying degrees, and MAP was significantly increased. In the observation group, hs-CRP, PCT, IL-6, SOFA score, MAP, and norepinephrine dosage showed statistical significance at 24 hours after treatment as compared with before treatment [hs-CRP (mg/L): 125.0 (105.0, 171.2) vs. 280.5 (213.2, 313.8), PCT (μg/L): 51.0 (20.0, 62.8) vs. 71.0 (10.8, 100.0), IL-6 (ng/L): 1 762.2 (300.8, 4 327.5) vs. 4 447.5 (630.4, 5 000.0), SOFA score: 13.0 (12.0, 14.0) vs. 16.0 (15.0, 17.0), MAP (mmHg, 1 mmHg ≈ 0.133 kPa): 79.00±12.87 vs. 65.20±11.70, norepinephrine dosage (μg×kg^-1×min^-1): 0.82±0.33 vs. 1.63±0.51, all P < 0.05]. In the control group, PCT and MAP showed statistical significance after 48 hours of treatment as compared with before treatment. Compared with the control group, hs-CRP, SOFA score and norepinephrine dosage after 48 hours of treatment in the observation group were significantly decreased [hs-CRP (mg/L): 87.2 (74.2, 126.0) vs. 157.0 (88.0, 200.0), SOFA score: 11.0 (10.0, 12.0) vs. 12.0 (10.0, 14.0), norepinephrine dosage (μg×kg^-1×min^-1): 0.51±0.37 vs. 0.81±0.58, all P < 0.05], MAP was significantly increased (mmHg: 82.00±8.71 vs. 77.77±7.80, P < 0.05). CONCLUSION In the treatment of CRRT, oXiris filter can reduce the short-term mortality of SA-AKI patients, lower inflammatory mediators levels and improve hemodynamics, showing therapeutic advantages over conventional filters.
Humans ; Acute Kidney Injury/etiology* ; Sepsis/therapy* ; Prospective Studies ; Interleukin-6 ; Continuous Renal Replacement Therapy/methods* ; C-Reactive Protein ; Male ; Female ; Middle Aged ; Hemodynamics ; Procalcitonin ; Aged

OBJECTIVE: To investigate the predictive value of inflammatory indicator and serum cystatin C (Cys C) for the prognosis of patients with sepsis-associated acute kidney injury (SA-AKI). METHODS: A prospective observational study was conducted. Patients with SA-AKI admitted to the intensive care unit (ICU) of the General Hospital of Ningxia Medical University from January 2022 to December 2023 were selected as the study subjects. General patient data, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II), inflammatory indicator, and serum Cys C levels were collected. The 28-day survival status of the patients was observed. A multivariate Logistic regression model was used to analyze the risk factors affecting the poor prognosis of SA-AKI patients. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive efficacy of each risk factor for the prognosis of SA-AKI patients. RESULTS: A total of 111 SA-AKI patients were included, with 65 patients (58.6%) in the survival group and 46 patients (41.4%) in the death group. The SOFA score, APACHE II score, interleukin-6 (IL-6), procalcitonin (PCT), hypersensitive C-reactive protein (hs-CRP), and serum Cys C levels in the death group were significantly higher than those in the survival group [SOFA score: 15.00 (14.00, 17.25) vs. 14.00 (11.00, 16.00), APACHE II score: 26.00 (23.75, 28.00) vs. 23.00 (18.50, 28.00), IL-6 (ng/L): 3 731.00±1 573.61 vs. 2 087.93±1 702.88, PCT (μg/L): 78.19±30.35 vs. 43.56±35.37, hs-CRP (mg/L): 266.50 (183.75, 326.75) vs. 210.00 (188.00, 273.00), serum Cys C (mg/L): 2.01±0.61 vs. 1.62±0.50, all P < 0.05]. Multivariate Logistic regression analysis showed that SOFA score [odds ratio (OR) = 1.273, 95% confidence interval (95%CI) was 1.012-1.600, P = 0.039], IL-6 (OR = 1.000, 95%CI was 1.000-1.001, P = 0.043), PCT (OR = 1.018, 95%CI was 1.002-1.035, P = 0.030), and Cys C (OR = 4.139, 95%CI was 1.727-9.919, P = 0.001) were independent risk factors affecting the 28-day prognosis of SA-AKI patients. ROC curve analysis showed that the area under the curve (AUC) of SOFA score, IL-6, PCT, and Cys C in predicting the 28-day prognosis of SA-AKI patients were 0.682 (95%CI was 0.582-0.782, P = 0.001), 0.753 (95%CI was 0.662-0.843, P < 0.001), 0.765 (95%CI was 0.677-0.854, P < 0.001), and 0.690 (95%CI was 0.583-0.798, P = 0.001), respectively. The combined predictive value of these four indicators for the prognosis of SA-AKI patients were superior to that of any single indicator, with an AUC of 0.847 (95%CI was 0.778-0.916, P < 0.001), a sensitivity of 95.7%, and a specificity of 56.9%. CONCLUSION The combination of SOFA score, IL-6, PCT, and Cys C provides a reliable predictive value for the prognosis of SA-AKI patients.
Humans ; Acute Kidney Injury/mortality* ; APACHE ; C-Reactive Protein ; Cystatin C/blood* ; Interleukin-6/blood* ; Logistic Models ; Predictive Value of Tests ; Procalcitonin/blood* ; Prognosis ; Prospective Studies ; Risk Factors ; ROC Curve ; Sepsis/mortality*

Human alphaherpesvirus 2 (HSV-2) is the main pathogen resulting human genital herpes, which poses a major threat to the socio-economic development, while there is no effective vaccine. In this study, we developed a novel lipopolyplex (LPP)-delivered mRNA vaccine expressing the HSV-2 envelope glycoprotein gD and evaluated its immunogenicity in mice. The mRNA vaccine was prepared from the genetically modified gD mRNA synthesized in vitro combined with the LPP delivery platform and it was named gD-ORI mRNA. The expression of gD antigen in the mRNA vaccine was validated in vitro by Western blotting and indirect immunofluorescence assay, then the immune responses induced by this mRNA vaccine in mice were evaluated. The immunization with gD mRNA alone induced strong humoral and cellular immune responses in mice. Robust and long-lasting gD-specific IgG antibodies were detected in the mouse serum after booster immunization with gD-ORI mRNA. The immunized mice exhibited a Th1/Th2 balanced IgG response and robust neutralizing antibodies against HSV-2, and a clear dose-response relationship was observed. The gD-specific IgG antibodies were maintained in mice for a long time, up to 18 weeks post-booster immunization. At the same time, multifunctional gD-specific CD4⁺ and CD8⁺ T cells in vaccinated mice were detected by intracellular cytokine staining (ICS). This novel gD-expressing mRNA vaccine delivered by LPP induces strong and long-lasting immune responses in mice post booster immunization and has a promising prospect for development and application. This study provides scientific evidence and reference for the development of a new mRNA vaccine for HSV-2.
Animals ; Herpesvirus 2, Human/genetics* ; Viral Envelope Proteins/genetics* ; Mice ; Herpes Genitalis/immunology* ; RNA, Messenger/immunology* ; Female ; Mice, Inbred BALB C ; Antibodies, Viral/blood* ; mRNA Vaccines/immunology* ; Antibodies, Neutralizing/blood* ; Humans

Over the years of exploration and development, the surgical techniques and prognosis of liver transplantation in China have been significantly improved, resulting in a notable decrease in the prevalence of postoperative complications. However, ischemic-type biliary lesion remain a non-negligible issue. The Third Affiliated Hospital of Sun Yat-sen University formulated and published the "Expert Consensus on the Diagnosis and Treatment of Ischemic-Type Biliary Lesions after Liver Transplantation in Mainland China" in 2015, which has now been updated into a guideline based on current conditions and literature reports. This guideline elaborates in detail on the definition, incidence, pathogenesis, diagnosis, prevention of high-risk factors, and treatment of ischemic-type biliary lesion, aiming to provide standardized and normative guidance for the diagnosis and treatment of ischemic-type biliary lesion after liver transplantation, thereby reducing the rate of re-transplantation and fatality, and to improve the overall quality of life of liver transplant recipients.

Objective: To investigate the effects of 3-phosphoinositide-dependent protein kinase-1(PDK1) on the purkinje cells(PCs) in aging mice. Methods: The footprint test, elevated beam-walk test and rotarod test were used to measure the gait traits, motor balance and motor coordination of mice. Immunoflourescence was used to detect the structure of the cerebellum and the morphology of cells in the cerebellum. The expression level of PDK1, protein kinase C gamma(PKCγ) and protein kinase B(also known as AKT) and the phosphorylation of ribosomal protein S6(rpS6) in the cerebellum were detected by Western blot. Results: The mice showed motor defects in the overlap between forelimb and hindlimb, motor balance and motor coordination ability in an age-dependent manner. Furthermore, the cerebellum and the soma size of the PCs decreased in an age-dependent manner. However, the density of the PCs was not affected by age. Additionally, the expression level of the PDK1, PKCγ, AKT and the phosphorylation of rpS6 in the cerebellum were reduced with age. Conclusion The cerebellar size and the cell soma size of PCs decrease in the old mice. These effects may contribute to the reduction of the expression of PKCγ and AKT and the phosphorylation of rpS6 in the old mice, ultimately affecting the cerebellar motor coordination.

By reviewing the ancient and modern literature， the name， origin， scientific name evolution， place of origin， quality， harvesting， processing， efficacy and toxicity of Asteris Radix et Rhizoma（ARR） were systematically sorted out， so as to provide reference for the development and utilization of the relevant famous classical formulas. According to textual research， ARR was first contained in Shennong Bencaojing， all generations are Ziwan for its proper name， and there are still aliases such as Ziyuan， Ziqian and Xiaobianer. Its mainstream origin in successive generations was Aster tataricus， and there are also Ligularia fischeri and others in local area of use. The medicinal parts of ARR are root and rhizome， but in modern times， the rhizome is mostly used for propagation and cultivation， so some of ARR medicinal materials only have the root without the rhizome. The earliest recorded ancient origin of ARR was now Fangxian（Hubei）， Zhengding and Handan（Heibei）， then the range of production areas gradually expanded， the mainstream production areas from the Song dynasty to the Ming and Qing dynasties included Hebei， Jiangsu， Anhui， Henan and other places， since modern times， two major producing areas have been formed in Anguo， Hebei province and Bozhou， Anhui province. From the quality evaluation， it is clear that from ancient times， flexible roots and purple color are the best. The ancient harvesting was mainly in lunar February or March， and then dried in the shade， and the modern harvesting is mostly in spring and autumn， and the roots are braided into pigtails and then dried in the sun or dried in the sun after 1-2 d. The ancient and modern processing method of ARR are basically the same， mainly honey processing， there are still methods of frying， steaming， vinegar sizzling， etc. Based on the results， it is recommended that the dried roots and rhizomes of A. tataricus should be used in clinical and the development of related famous classical formulas， and those whose original formulas specify the processing requirements can be processed according to the relevant requirements， while whose processing requirements are not specified should be used in the form of raw products.

Sepsis is caused by infection, which can ultimately lead to multiple organ dysfunction and even life-threatening. Early recognition and early treatment can significantly improve the prognosis of sepsis patients. However, the effect of using a single biomarker for early diagnosis of sepsis is still not ideal. In recent years, researchers have turned their attention to artificial intelligence technology for early diagnosis of sepsis. This paper briefly introduces the advantages and disadvantages of sepsis related inflammatory indicators, biomarkers, and scoring systems of disease severity for early identification of sepsis, and focuses on the research progress and limitations of artificial intelligence technology for early diagnosis of sepsis, aiming to seek new methods and ideas for early diagnosis of sepsis.

Objective To explore the underlying mechanism of β2 adrenergic receptor(ADRB2)in fibrogenesis during wound healing.Methods Non-specific ADRB2 gene knockdown adeno-associated virus(AAV-ADRB2 group,6 mice)and control virus(AAV-NC group,6 mice)was injected randomly into the back skin of 12 mice for 21 days,a full-thickness skin defected wound healing murine model was established.Wound healing rates were recorded at the 1st,3rd,5th,and 7th day after operation.Histological examinations by H-E staining,Masson staining,and immunohistochemistry were conducted to observe wounded skin tissue structure,fibrosis,and α-SMA protein expression;quantitative PCR was employed to analyze ADRB2 and matrix metalloproteinase(MMP)mRNA levels;Western blotting was utilized to assess the protein expression levels of COL1A1,COL3A1,TGF-β1,and Smad3.Results On postoperative day 5 and 7,the wound healing rate of the AAV-ADRB2 group significantly decreased(P＜0.05),accompanied by a series pathological changes,including thickened epidermis,exaggerated inflammation,reduced fibroblast count,and inhibited collagen deposition;the α-SMA expression showed a significant decrease(P＜0.05),and the ratio of COL1A1 to COL3A1 decreased(P＜0.05);ADRB2 mRNA levels significantly decreased(P＜0.01),while MMP-1 and MMP-8 mRNA levels increased(P＜0.01);the protein levels of TGF-β1 and Smad3 exhibited a significant decrease(P＜0.05).Conclusions ADRB2 knockdown reduced fibrosis during wound healing and degenerated connective tissue content around the wound bed by inhibiting the TGF-β1/Smad3 signaling pathway,which leads to an increase in MMP mRNA levels and a decrease in the ratio of type Ⅰ to type Ⅲ collagen.

Objective The prediction of RR intervals in hypertensive patients can help clinicians to analyze and warn patients'heart condition.Methods Using 8 patients'data as samples,the RR intervals of patients were predicted by long short-term memory network(LSTM)and gradient lift tree(XGBoost),and the prediction results of the two models were combined by the inverse variance method to overcome the disadvantage of single model prediction.Results Compared with the single model,the proposed combined model had a different degree of improvement in the prediction of RR intervals in 8 patients.Conclusion LSTM-XGBoost model provides a method for predicting RR intervals in hypertensive patients,which has potential clinical feasibility.

Humans ; Waldenstrom Macroglobulinemia/genetics* ; East Asian People ; Chromosome Aberrations ; Lymphoma