Salvianolic Acid F Regulates Bax/Caspase-3/GSDME Signaling Pathway to Inhibit Pyroptosis of HK-2 Cells / 中国实验方剂学杂志

ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

Encefalitis autoinmune posherpética. Caso clínico pediátrico / Autoimmune post-herpes simplex encephalitis. A pediatric clinical case report

La encefalitis por virus herpes simple (VHS) es una causa frecuente de encefalitis grave y potencialmente fatal. La encefalitis autoinmune posherpética (EAPH) afecta a un porcentaje de los pacientes que han presentado encefalitis herpética (EH) y se caracteriza por la aparición de nuevos síntomas neurológico/psiquiátricos, y/o por el empeoramiento de los déficits adquiridos durante la infección viral dentro de un lapso temporal predecible. Se produce por un mecanismo no relacionado con el VHS, sino por fenómenos autoinmunes, y es susceptible de tratamiento con inmunomoduladores. Se presenta el caso de un varón de 5 años de edad con EAPH que requirió tratamiento inmunomodulador, de primera y segunda línea, con buena evolución y remisión de los síntomas.

Herpes simplex virus (HSV) encephalitis is a common cause of severe and potentially fatal encephalitis. Autoimmune post-herpes simplex encephalitis (AIPHSE) affects a percentage of patients who developed herpes simplex encephalitis (HSE) and is characterized by the onset of new neurological/psychiatric symptoms and/or worsening of deficits acquired during the herpes infection within a predictable time frame. It is caused by a mechanism not related to HSV, but by autoimmune conditions, and is susceptible to treatment with immunomodulators. Here we describe the case of a 5-year-old boy with AIPHSE who required first- and second-line immunomodulatory treatment, with an adequate course and remission of symptoms.

Secuelas cognitivas en encefalitis inmunomediadas: cohorte de pacientes en Argentina / Cognitive sequelae in immunomediated encephalitis: cohort of patients in Argentina

Resumen Introducción: Las encefalitis inmunomediadas son un desorden neurológico de origen autoinmune. Actual mente es escasa la descripción de las secuelas cognitivas crónicas. El objetivo del presente trabajo fue caracterizar la secuela cognitiva de diferentes tipos de encefalitis inmunomediadas en una cohorte de un centro único de Argentina. Métodos: Estudio prospectivo, observacional, trans versal, de pacientes en seguimiento en un hospital de la Ciudad de Buenos Aires, con diagnóstico de encefalitis inmunomediada probable y definitiva. Se evaluaron variables epidemiológicas, clínicas, paraclínicas y tra tamiento. Se determinó la secuela cognitiva a través de una evaluación neurocognitiva realizada a partir del año de la presentación clínica. Resultados: Fueron incluidos 15 pacientes, todos con resultado disminuido en al menos un test. La memoria fue el dominio más afectado. Aquellos que se encon traban bajo tratamiento inmunosupresor al momento de evaluarse presentaron menores resultados en el aprendizaje seriado (media -2.94; desvío estándar 1.54) versus los que se encontraban sin tratamiento (media -1.18; desvío estándar 1.40; p = 0.05) y en la prueba de reconocimiento (media -10.34; desvío estándar 8.02) ver sus sin tratamiento (media -1.39; desvío estándar 2.21; p = 0.003). Los pacientes con estatus epiléptico tuvieron resultados deficitarios en la prueba de reconocimiento (media -7.2; desvío estándar 7.91) en comparación a los que no lo tenían (media -1.47; desvío estándar 2.34; p = 0.05). Conclusión: Nuestros resultados demuestran que, a pesar del curso monofásico de la enfermedad, todos los pacientes presentan daño cognitivo persistente más allá del año del inicio del cuadro. Estudios prospectivos de mayor envergadura serían necesarios para confirmar nuestros hallazgos.

Abstract Introduction: Autoimmune encephalitis represents a group of immune-mediated neurological disorders. At present, the description of the chronic cognitive sequela is scarce. The objective of this study was to characterize the cognitive after effects of different types of autoimmune encephalitis in a cohort from a single center in Argentina. Methods: Prospective, observational, cross-sectional study of patients under follow-up at a hospital in Buenos Aires city, with a diagnosis of probable and definitive immune-mediated encephalitis. Epidemiological, clini cal, paraclinical and treatment related variables were evaluated. Cognitive sequela was determined through a neurocognitive evaluation performed at least a year after the clinical presentation. Results: Fifteen patients were included. All had di minished results in at least one test. Memory was the most affected domain. Patients who were under im munosuppressive treatment at the time of evaluation presented lower results in serial learning (mean -2.94; standard deviation 1.54) versus those who weren't under treatment (mean -1.18; standard deviation 1.40; p = 0.05). The same pattern was observed on the recognition test of treatment group (mean -10.34; standard deviation 8.02) versus treatment-free group (mean -1.39; standard deviation 2.21; p =0.003). Patients with status epilepticus had poorer results in the recognition test (mean -7.2; standard deviation 7.91) compared to those without it (mean -1.47; standard deviation 2.34; p = 0.05). Conclusion: Our results show that, despite the mo nophasic course of this disease, all patients had persis tent cognitive damage beyond the year of onset. Larger prospective studies are required to confirm our findings.

Regulación del calcio por SERC-A antes de la enfermedad de Alzheimer y durante la misma / Calcium regulation by SERC-A before and during Alzheimer disease

Hay muchos factores implicados en la incidencia de la enfermedad de Alzheimer que, en combinación, terminan por impedir o dificultar las funciones neuronales normales. Actualmente, poco se conoce sobre la regulación del calcio, antes de la enfermedad y durante la misma. La inestabilidad interna de los niveles de calcio se asocia a un mayor riesgo vascular, condición prevalente en un gran número de individuos ya comprometidos por la enfermedad de Alzheimer. Esta revisión proporciona una reevaluación de los mecanismos moleculares de la ATPasa dependiente de Ca2+ del retículo sarcoendoplásmico (SERC-A) en la enfermedad y analiza los aspectos más destacados de la función de los canales de calcio dependientes de voltaje; de esta manera, se podrán abrir nuevas alternativas de tratamiento. Estos mecanismos de regulación son clínicamente relevantes, ya que se ha implicado la función irregular de SERC-A en diversas alteraciones de la función cerebral.

There are many factors involved in the incidence of Alzheimer's disease that, in combination, impede or hinder normal neuronal functions. Little is currently known about calcium regulation before and during the disease. Internal instability of calcium levels is associated with increased vascular risk, a prevalent condition in a high number of individuals already compromised by Alzheimer's disease. This review provides a reevaluation of the molecular mechanism of the sarcoendoplasmic reticulum calcium ATPase (SERC-A) in the disease and discusses salient aspects of voltage-gated calcium channel function; in these way new alternatives could be open for its treatment. These regulation mechanisms are clinically relevant since the irregular functions of SERC+A has been implicated in pathologies of brain function.

Predictive value of preoperative liver function for perioperative massive blood transfusion in patients undergoing ascending aorta surgery / 中国输血杂志

【Objective】 To explore the predictive value of preoperative liver function for massive blood transfusion (MBT) in patients undergoing ascending aorta surgery. 【Methods】 Data from 238 patients undergoing ascending aorta surgery in the Department of Cardiovascular Surgery at The Affiliated Lihuili Hospital of Ningbo University were collected. Preoperative liver function tests were performed for all patients. Based on the perioperative transfusion volumes of red blood cell suspension, patients were divided into the MBT group, non-MBT group, and no blood transfusion (NBT) group. Clinical data during the perioperative period were compared among different groups. Receiver operating characteristic curve (ROC curve) analysis was used to assess the predictive value of liver function indicators for MBT and determine cut-off values. 【Results】 Compared with the non-MBT group and NBT group, the MBT group showed statistically significant differences in preoperative levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), direct bilirubin (DBIL), and serum albumin (SA) (P28.50 U/L, ALT >40.00 U/L, SA ≤34.55 g/L, and DBIL >4.25 μmol/L, there was a significant increase in the transfusion volume of various blood components and the incidence of MBT. 【Conclusion】 Preoperative liver function indicators (AST, ALT, SA, DBIL) have a moderate predictive value for MBT in patients undergoing ascending aorta surgery.

Effect of Suanzaoren Decoction on expression of ionotropic glutamate receptors and synaptic plasticity in hippocampus of anxiety rats / 中国中药杂志

This study investigated the effect of Suanzaoren Decoction on the expression of N-methyl-D-aspartate receptors(NMDAR) and α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptors(AMPAR) in the hippocampus and synaptic plasticity in rats with conditioned fear-induced anxiety. The effect of Suanzaoren Decoction on rat behaviors were evaluated through open field experiment, elevated plus maze experiment, and light/dark box experiment. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of glutamate(Glu) and γ-aminobutyric acid(GABA) in the rat hippocampus. Real-time fluorescence quantitative PCR(qRT-PCR) and Western blot were employed to assess the gene and protein expression of ionotropic glutamate receptors in the hippocampal region. Transmission electron microscopy was utilized to observe the changes in the ultrastructure of synaptic neurons in the hippocampal region. Long-term potentiation(LTP) detection technique was employed to record the changes in population spike(PS) amplitude in the hippocampal region of mice in each group. The behavioral results showed that compared with the model group, the Suanzaoren Decoction group effectively increased the number of entries into open arms, time spent in open arms, percentage of time spent in open arms out of total movement time, number of entries into open arms out of total entries into both arms(P<0.01), and significantly increased the time spent in the light box and the number of shuttle crossings(P<0.01). There was an increasing trend in the number of grid crossings, entries into the center grid, and time spent in the center grid, indicating a significant anxiolytic effect. ELISA results showed that compared with the model group, the Suanzaoren Decoction group exhibited significantly reduced levels of Glu, Glu/GABA ratio(P<0.01), and significantly increased levels of GABA(P<0.01) in the rat hippocampus. Furthermore, Suanzaoren Decoction significantly decreased the gene and protein expression of NMDAR(GluN2B and GluN2A) and AMPAR(GluA1 and GluA2) compared with the model group. Transmission electron microscopy results demonstrated improvements in synapses, neuronal cells, and organelles in the hippocampal region of the Suanzaoren Decoction group compared with the model group. LTP detection results showed a significant increase in the PS amplitude changes in the hippocampal region of Suanzaoren Decoction group from 5 to 35 min compared with the model group(P<0.05, P<0.01). In conclusion, Suanzaoren Decoction exhibits significant anxiolytic effects, which may be attributed to the reduction in NMDAR and AMPAR expression levels and the improvement of synaptic plasticity.

Mechanism of Shenqi Yiliu Prescription Combined with Cisplatin on H22 Liver Cancer-bearing Mice Based on NLRP3/Caspase-1/GSDMD Pyroptosis Pathway / 中国实验方剂学杂志

ObjectiveTo explore the anti-tumor effect and mechanism of Shenqi Yiliu prescription in the intervention of pyroptosis. MethodTen male BALB/c mice were randomly selected and assigned to the blank group. The remaining 40 mice underwent the induction of the liver cancer xenograft model. After 5 days of modeling， 40 surviving mice were randomly divided into model group， cisplatin group ［2.5×10-3 g·kg-1·（3 d）-1］， Shenqi Yiliu prescription group （27 g·kg-1·d-1）， and a combination group （Shenqi Yiliu prescription group + cisplatin）. The mice in the blank group and the model group were treated with an equal volume of normal saline for 10 days. The general conditions of mice in each group were observed. After the intervention， the tumor weight of the mice was weighed and the tumor inhibition rate was calculated. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in tumor tissues. The levels of mouse liver function indicators， including alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were detected. The TdT-mediated dUTP-biotin nick end labeling （TUNEL） assay was used to detect DNA damage in mouse tumor tissue cells. Immunohistochemistry （IHC）， immunofluorescence （IF）， and Western blot were used to detect the protein expression levels of NOD-like receptor protein 3 （NLRP3）， cysteinyl aspartate-specific protease-1 （Caspase-1）， and gasdermin D （GSDMD） in tumor tissues. The levels of interleukin-1β （IL-1β） and interleukin-18 （IL-18） in tumor tissues were detected by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with the mice in the blank group， those in the model group were in a poor mental state， sleepy， and lazy， and their fur color was dull， with increased levels of serum ALT and AST in liver function tests （P<0.01）. Compared with the model group， the groups with drug intervention showed improved mental state， inhibited tumor growth to varying degrees， and decreased tumor weight， and the tumor inhibition rate in the combination group was the highest （P<0.01）. HE staining showed that the pathological and morphological lesions of the tumor tissues in the model group were significant， while those in all groups with drug intervention were improved to a certain extent. The karyolysis and nuclear rupture in the Shenqi Yiliu prescription group and the combination group were more significant. In the liver function test， the serum ALT and AST levels of mice in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the inflammatory factors IL-1β and IL-18 in each group with drug intervention decreased （P<0.05， P<0.01）. Among them， the declining trend of IL-1β and IL-18 in the Shenqi Yiliu prescription group was the most significant （P<0.01）. TUNEL staining showed that the positive TUNEL staining in each group with drug intervention decreased after intervention （P<0.05， P<0.01）， especially the cisplatin group and Shenqi Yiliu prescription group （P<0.01）. Western blot， IHC， and IF found that the protein expression levels of NLRP3， Caspase-1， and GSDMD in each group with drug intervention decreased （P<0.05， P<0.01）. Compared with the mice in the cisplatin group， those in the Shenqi Yiliu prescription group and the combination group had better mental state and regular tumor morphology， and the tumor weight of the mice in the combination group decreased （P<0.05）. The levels of ALT and AST in the Shenqi Yiliu prescription group decreased （P<0.05）， and the levels of IL-1β and IL-18 in the Shenqi Yiliu prescription group and the combination group decreased （P<0.05， P<0.01）， especially in the combination group （P<0.01）. The results of IHC showed that the expression of GSDMD protein in the tumor tissues of mice in the combination group was reduced （P<0.01）. IF detection showed that the expression of NLRP3 in the tumor tissues of the Shenqi Yiliu prescription group was reduced （P<0.01）. The results of Western blot showed that the expression level of NLRP3 protein in the Shenqi Yiliu prescription group and the combination group decreased （P<0.01）， and the expression level of Caspase-1 protein in the combination group decreased （P<0.01）. The decrease in GSDMD protein expression was not significant， and the difference was not statistically significant. ConclusionShenqi Yiliu prescription combined with cisplatin has an obvious anti-tumor effect， which may be achieved by down-regulating the NLRP3/Caspase-1/GSDMD inflammatory pyroptosis pathway to inhibit cell pyroptosis， and relieve the inflammatory response in mice with liver cancer.

Exploring the effect of Tuina on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation based on NR2B/PSD-95 pathway / 针灸推拿医学（英文版）

Objective: To investigate the analgesic mechanism of Tuina (Chinese therapeutic massage) by observing the effect of the N-methyl-D-aspartate receptor subunit 2B (NR2B)/postsynaptic density-95 (PSD-95) pathway on the dendritic structure of spinal cord dorsal horn in rats with lumbar disc herniation. Methods: Fifty Sprague-Dawley rats were randomly divided into a blank group, a model group, a Tuina group, a blocker agent group, and a blocker agent + Tuina group. The sciatic nerve chronic constriction injury (CCI) model was prepared by the sciatic nerve ligation method. From the 4th day after modeling, rats in the Tuina group and the blocker agent + Tuina group were subject to daily Tuina intervention, and those in the blocker agent group and the blocker agent + Tuina group were daily intrathecally injected with NR2B blocker agent (MK-801). The spontaneous pain score was used to observe the pain behavior of all rats. The expression levels of NR2B and downstream PSD-95 were measured by immunohistochemistry, and the dendritic structure changes were observed by Golgi staining for rat spinal cord dorsal horn after 14 d of continuous intervention. Results: Compared with the blank group, the degree of rat spontaneous pain after CCI was elevated in both the model and the Tuina groups (P<0.01) and was reduced in the Tuina group after the Tuina intervention compared with the model group (P<0.05). Compared with the model group, the rat spontaneous pain level after blocking NR2B was reduced in both the blocker agent group and the blocker agent + Tuina group (P<0.05). The NR2B and PSD-95 protein levels were significantly higher in the model group compared with the blank group (P<0.01); the total number of dendritic branches was increased (P<0.01), and the total dendritic length became longer (P<0.01) in the spinal cord dorsal horn. The rat NR2B and PSD-95 protein levels were significantly decreased in the Tuina group compared with the model group (P<0.01); the total dendritic branch number was reduced (P<0.01) and the total length was shortened (P<0.01) in the spinal cord dorsal horn. After blocking NR2B, the expression levels of NR2B and downstream PSD-95 protein were significantly lower in both the blocker agent group and the blocker agent + Tuina group compared to the model group (P<0.01). The total branch number was significantly reduced (P<0.01), and the total length was significantly shortened (P<0.01) of the dendrites in the spinal cord dorsal horn. Conclusion: Tuina may exert an analgesic effect by remodeling the dendritic structure in the spinal cord dorsal horn in rats with lumbar disc herniation, and its mechanism may be related to the inhibition of NR2B/PSD-95 signaling pathway.

Advances in relapse risk factors of anti-N-methyl-D-aspartate receptor encephalitis / 中华神经科杂志

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune encephalitis mediated by anti-NMDAR antibody. Current studies have found that most patients with anti-NMDAR encephalitis have a good prognosis after immunotherapy and tumor therapy, but there are still 4.5%-36.4% patients with relapse. It is important to identify the risk factors for the prevention of relapse. This article aims to review the relapse risk factors of NMDAR encephalitis in order to provide help for the prevention of relapse.

Sound touch elastography linear combined with ultrasound score for staging liver fibrosis in patients with chronic hepatitis B / 中华超声影像学杂志

Objective:To study the value of sound touch elastography (STE) linear combined with ultrasound score (US) in the diagnosis of chronic hepatitis B (CHB) liver fibrosis, and to investigate whether their combination can improve the diagnostic efficiency of subdividing the degree of CHB liver fibrosis. Furthermore, a comparison with STE linear combined with the serological model was performed to seek the optimal linear combination model.Methods:A total of 313 subjects were enrolled from September 2018 to December 2021 in Shenzhen Third People′s Hospital Affiliated to Guangdong Medical University, including 259 patients with CHB who had completed liver biopsy and 54 healthy volunteers. CHB patients were divided into liver fibrosis group (F1-F4 group) according to METAVIR classification standard, and healthy volunteers were used as the control group. All subjects underwent liver ultrasound examination, STE and blood biochemical indexes of liver function. The US was performed according to the liver ultrasound examination, and the liver stiffness measurement (LSM) was measured by STE, aspartate aminotransferase and platelet ratio index (APRI) was calculated by blood biochemical index. Fisher discriminant analysis was used to establish the linear combination (LC) diagnostic marker of US and LSM, and the linear combination (LC2) diagnostic marker of LSM and APRI, successively. Spearman rank correlation coefficient was used to analyze the correlations between US, LSM, APRI, LC2, LC and pathological results. The ROC curves of US, LSM, APRI, LC2 and LC for diagnosing CHB liver fibrosis were plotted, and the diagnostic efficiency of above diagnostic markers was evaluated according to the accuracy, sensitivity, specificity and area under the ROC curve (AUC).Results:The formula for the linear combination of US and LSM was LC=0.986 0×US+ 0.166 7×LSM, and LC was highly positively correlated with pathological findings ( rs=0.851, P<0.001), higher than US, LSM, LC2 and APRI ( rs=0.825, 0.775, 0.802, 0.586, all P<0.001). LC showed the best diagnostic efficiency. The AUCs for diagnosing ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis were 0.945, 0.911, 0.954, 0.955, respectively, which superior to the AUCs of US (0.913, 0.879, 0.934 and 0.916, respectively), the AUCs of LSM (0.860, 0.871, 0.934 and 0.952, respectively) and the AUCs of LC2(0.899, 0.883, 0.941, 0.946, respectively). Compared with US, the AUC of LC diagnosis of ≥F1, ≥F2, ≥F3 liver fibrosis and =F4 cirrhosis increased by 3.2%, 3.2%, 2.0% and 3.9%, respectively, with all significant differences ( P<0.05). Compared with LSM, the AUC of LC increased by 8.5%, 4.0%, 2.0% and 0.3%, respectively, with significant difference ( P<0.05) except for stage =F4 cirrhosis.Compared with LC2, the AUC of LC increased by 4.6%, 2.8%, 1.3% and 0.9%, respectively, and there were significant differences in the diagnosis of ≥F1 and ≥F2 liver fibrosis ( P<0.05). Moreover, the overall efficiency of LC2 was not significantly improved than LSM, the difference was not significant ( P>0.05). Conclusions:US, LSM, LC2 and LC can be used to diagnose the degree of CHB liver fibrosis, but LC is better than US or LSM and LC2 alone, especially in the subdivision of mild liver fibrosis, which is a promising new diagnostic marker to subdivide the degree of CHB liver fibrosis.

Value of liver ultrasonic elasticity index combined with APRI, FIB-4 and GP in the diagnosis of autoimmune hepatitis complicated with liver cirrhosis / 中国医师杂志

Objective:To investigate the value of liver ultrasonic elasticity index combined with aspartate aminotransferase to platelet ratio index (APRI), fibrosis index based on the four factors (FIB-4) and globulin platelet model (GP) in the diagnosis of autoimmune hepatitis complicated with liver cirrhosis.Methods:From January 2020 to January 2022, 82 patients with autoimmune hepatitis and cirrhosis treated in West China Hospital of Sichuan University were selected as observation group, and 90 patients with autoimmune hepatitis were selected as controls (control group). All of them underwent liver ultrasound elastic examination, and the APRI, FIB-4, GP of patients were calculated. The differences of shear wave velocity (SWV), liver hardness value (LSM), strain rate ratio (SR), APRI, FIB-4, GP between the two groups were compared. At the same time, the differences of SWV, LSM, SR, APRI, FIB-4 and GP among patients with autoimmune hepatitis with different degrees of liver fibrosis and inflammation were analyzed. The value of liver ultrasound elasticity index, APRI, FIB-4 and GP in predicting autoimmune hepatitis complicated with cirrhosis was evaluated by the receiver operating characteristic (ROC) curve.Results:The SWV, LSM, FIB-4 and GP in the observation group were (1.60±0.21)m/s, (13.98±1.82)kPa, (8.10±1.43) and (4.15±1.05) respectively, which were significantly higher than those in the control group (all P<0.05), while SR and APRI were (5.04±0.98) and (2.41±0.92) respectively, which were significantly lower than those in the control group (all P<0.05). With the aggravation of liver fibrosis, the levels of SWV, LSM, FIB-4 and GP in patients with autoimmune hepatitis were higher (all P<0.05), while the SR and APRI were lower (all P<0.05). There was no statistically significant difference in SWV, LSM, SR, APRI, FIB-4 and GP between patients with G1-G2 and G3-G4 inflammatory degree of autoimmune hepatitis (all P>0.05). SWV, LSM, SR, APRI, FIB-4 and GP were included in the binary logistic regression analysis, and SWV, FIB-4 and GP were finally selected as independent predictors for diagnosis of autoimmune hepatitis with cirrhosis (all P<0.05). The area under the ROC curve of combined prediction of SWV, FIB-4 and GP for autoimmune hepatitis with cirrhosis was 0.931, which was significantly higher than other indicators (all P<0.05), and the sensitivity and specificity were 95.00% and 84.00% respectively. Conclusions:Liver ultrasonic elasticity index, APRI, FIB-4 and GP are related to the degree of liver fibrosis in patients with autoimmune hepatitis. SWV, FIB-4 combined with GP have high application value in predicting autoimmune hepatitis complicated with liver cirrhosis.

Abnormal topology of cortical thickness covariance network and altered functional connectivity in patients with anti-N-methyl-D-aspartate receptor encephalitis / 中华行为医学与脑科学杂志

Objective:To explore the changes in topological attributes of structural covariance network based on cortical thickness and the brain functional activities in patients with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis by graph theory and functional connectivity (FC) analyses, and to investigate whether these changes were correlated to cognitive impairment.Methods:A total of 33 patients with anti-NMDAR encephalitis from Department of Neurology of the First Affiliated Hospital of Guangxi Medical University(patient group) and 35 healthy controls(control group) with matched gender, age, and education were included from July 2018 to November 2021.All subjects received cognitive function assessments, structural and functional magnetic resonance imaging scans.Structural covariance networks were constructed in the two groups based on cortical thickness values and topological characteristics of networks were computed.A non-parametric permutation test which repeated 1 000 times was used to compare the characteristics of the networks between the two groups.Brain regions with abnormal topology were defined as region of interest(ROI), and FC values in global brain level were calculated.SPM 12 and RESTplus were used to identify the brain regions with significant differences in FC values between the two groups.Finally, Spearman correlation analysis between FC values of significant brain regions and cognitive scores were performed by SPSS 24.0.Results:The cognitive score of patients with anti-NMDAR encephalitis (27.0(23.5, 28.0)) was lower than that in control group(29.0(27.0, 30.0)) ( Z=-3.029, P=0.002). Graph theory analysis found that the patients showed significantly increased clustering coefficients ( P=0.004) and decreased global efficiency ( P=0.004) compared with healthy controls.Moreover, the nodal efficiency of left ventral posterior cingulate cortex (vPCC) and right dorsal posterior cingulate cortex (dPCC), as well as the nodal degree centrality of left vPCC and left polar planum of superior temporal gyrus (ppSTG) in patient group were significantly decreased ( P<0.05, FDR corrected) compared with control group.FC analysis showed the increased FC values between left vPCC and posterior cerebellum (MNI: x=6, y=-66, z=-21), as well as between left ppSTG and anterior cerebellum (MNI: x=6, y=-54, z=-12) (GRF corrected, voxel level P<0.001, cluster level P<0.05) in patient grooup.The FC values between left vPCC and posterior cerebellum were negatively correlated with the cognitive scores ( r=-0.403, P=0.020). Conclusion:Patients with anti-NMDAR encephalitis show abnormal topology of structural covariance network based on cortical thickness and altered FC values, some of which are correlated to cognition and may be the underlying neural mechanism of cognitive impairment in patients with anti-NMDAR encephalitis.

Caudate nucleus and thalamus in untreated patients with obsessive-compulsive disorder: a magnetic resonance spectroscopy study / 中华行为医学与脑科学杂志

Objective:To investigate the neurobiochemical metabolites of caudate nucleus and thalamus in patients with obsessive-compulsive disorder and their relationship with obsessive-compulsive symptoms.Methods:From April 2019 to January 2022 in Beijing Anding Hospital, totally 25 untreated patients with obsessive-compulsive disorder were recruited, and 20 healthy controls matched with gender, age and educational background were recruited for the study.The maps of neurobiochemical metabolites of patients and normal controls were collected by hydrogen proton magnetic resonance spectroscopy.With bilateral caudate nucleus and thalamus as brain regions of interest.The relative concentrations of N-acetylaspartic acid (NAA), glutamic acid (Glu) and γ-aminobutyric acid (GABA) were fitted by LCModel software.At the same time, the clinical symptoms of patients were evaluated with Yale-Brown obsessive-compulsive scale (Y-BOCS) and Hamilton anxiety scale (HAMA). SPSS 20.0 software was used for statistical analysis.Independent double sample t-test was used to compare the differences of different nerve biochemical metabolite concentrations between patients with obsessive-compulsive disorders and healthy controls.Pearson correlation analysis was used to explore the correlation between biochemical metabolite concentrations and clinical symptoms. Results:The Glu concentration in the left thalamus of patients with obsessive-compulsive disorder (3.97±0.41) was higher than that of the control group (3.66±0.55)( t=-2.11, P<0.05), while the NAA concentration was (4.87±0.47)lower than that of the control group (5.15±0.44)( t=2.05, P<0.05). The GABA concentrations in the right caudate nucleus (0.50±0.18) and thalamus (0.80±0.19) were lower than those in the control group ((0.63±0.23), (0.96±0.24))( t=2.08, 2.36, both P<0.05). Pearson correlation analysis showed that the Glu concentration in the left caudate nucleus of patients with obsessive-compulsive disorder was positively correlated with the total score of Y-BOCS( r=0.46, P<0.05). Spearman correlation analysis showed that Glu concentration in the right caudate nucleus was positively correlated with the total score of HAMA in patients with obsessive-compulsive disorder ( r=0.46, P<0.05). Conclusion:NAA, Glu and GABA metabolism in caudate nucleus and thalamus are abnormal in patients with obsessive-compulsive disorder, and Glu concentration is positively correlated with the severity of obsessive-compulsive and anxiety symptoms.

Efficacy of peginterferon alfa-2a combined with entecavir in sequential treatment of chronic hepatitis B / 中国基层医药

Objective:To investigate the efficacy of peginterferon alfa-2a (Peg-IFNα-2a) combined with entecavir in sequential treatment of chronic hepatitis B.Methods:A total of 106 patients with chronic hepatitis B who received treatment in Affiliated Hangzhou Xixi Hospital of Zhejiang University School of Medicine from January 2020 to February 2022 were included in this study. They were divided into a control group (entecavir treatment, n = 53) and a study group (sequential therapy with Peg-IFNα-2a followed by entecavir, n = 53). Liver function indicators, liver fibrosis indicators, clinical treatment efficacy, and incidence of adverse reactions were compared between the two groups before and after treatment. Results:After treatment, total bilirubin, alanine aminotransferase and aspartate transaminase in the control and study groups were (94.79 ± 8.71) μmol/L and (67.67 ± 9.19) μmol/L, (256.93 ± 44.07) U/L and (186.56 ± 48.37) U/L, (256.47 ± 43.73) U/L and (200.69 ± 41.34) U/L, and they were (140.05 ± 26.15) μmol/L and (141.32 ± 25.35) μmol/L, (433.66 ± 77.16) U/L and (429.77 ± 73.73) U/L, (352.34 ± 65.19) U/L and (354.05 ± 66.13) U/L before the treatment. After treatment, these indexes in each group were decreased compared with before treatment ( t = 19.19, -12.13, -28.85, -20.96, -19.27, -12.03, all P < 0.05). After treatment, these indexes in the study group were significantly lower than those in the control group ( t = -6.49, -7.30, -6.74, all P < 0.001). After treatment, the levels of hyaluronic acid, laminin, type III procollagen peptide, and type IV collagen in the control and study groups were (124.91 ± 22.99) μg/L and (101.29 ± 22.67) μg/L, (132.71 ± 25.37) μg/L and (110.56 ± 25.49) μg/L, (116.93 ± 20.29) μg/L and (93.14 ± 20.39) μg/L, (63.14 ± 12.19) μg/L and (50.81 ± 11.63) μg/L, and they were (175.73 ± 48.56) μg/L and (177.61 ± 48.51) μg/L, (163.43 ± 41.52) μg/L and (165.57 ± 41.59) μg/L, (139.71 ± 31.75) μg/L and (141.72 ± 31.78) μg/L, (106.97 ± 32.24) μg/L and (104.02 ± 34.12) μg/L before treatment. After treatment, the levels of these indexes in each group were significantly decreased compared with before treatment ( t = -13.04, -8.68, -10.43, -5.82, -13.35, -6.26, -13.02, -10.72, all P < 0.05). After treatment, the levels of these indexes in the study group were significantly lower than those in the control group ( t = -5.32, -4.48, -6.02, -5.32, all P < 0.001). The total response rate in the study group was 88.68% (47/53), which was significantly higher than 62.26% (33/53) in the control group ( χ2 = 9.98, P < 0.05). The HBsAg conversion rate in the study group was 33.96% (18/53), which was significantly higher than 1.32% (6/53) in the control group ( χ2 = 7.75, P < 0.05). There was no statistically significant difference in the incidence of adverse reactions between the study and control groups [26.42% (14/53) vs. 30.19% (16/53), χ2 = 0.81, P > 0.05]. Conclusion:Sequential therapy with Peg-IFNα-2a followed by entecavir can effectively improve liver function,reduce liver fibrosis , improve clinical treatment efficacy, and will not increase adverse reactions.

Clinical analysis of 202 patients with drug-induced liver injury / 中国基层医药

Objective:To investigate the clinical characteristics of drug-induced liver injury and provide a theoretical basis for the prevention and treatment of drug-induced liver injury.Methods:The clinical data of 202 patients with complete information on drug-induced liver injury who received treatment in First Hospital of Shanxi Medical University from November 2018 to November 2021 were collected. The information including gender, age, type and name of drugs taken or exposed, clinical characteristics, autoantibodies, and liver function was statistically analyzed.Results:Among the 202 patients with drug-induced liver injury, 77 patients (38.1%) were male and 125 patients (61.9%) were female. Age distribution was mainly at > 40-60 years. There were 141 cases (69.8%) of hepatocellular type, 27 cases (13.4%) of cholestatic type, and 34 cases (16.8%) of mixed type. There were statistically significant differences in alanine aminotransferase, aspartate aminotransferase, γ-glutamine transferase, alkaline phosphatase, prothrombin time, international standardized ratio, and prothrombin activity between different clinical types ( H = 91.43, 58.65, 9.25, 32.69, 9.56, 8.19, 9.40, all P < 0.05). Among the 202 patients with drug-induced liver injury, severe liver injury occurred in the largest proportion of cases (40.6%). There was no significant difference in the disease severity between different clinical types ( P = 0.789). The top three types of drugs causing liver injury were traditional Chinese medicine [52.0% (105/202)], antineoplastic drugs [6.4% (13/202)], and antipsychotics [5.9% (12/202)]. The detection rate of autoantibodies in 202 patients with drug-induced liver injury was 29.7% (60/202). Conclusion:Drug-induced liver injury lacks specificity in clinical manifestations. A wide variety of drugs can cause liver injury. Clinicians should strengthen liver function monitoring in key populations. The proportion of patients with mixed-type liver failure is high, which should be taken seriously. When patients with drug-induced liver injury are positive for liver disease-related antibodies, clinicians should be vigilant about the possibility of drug-induced liver injury.

Correlation between peak viral load and liver function damage in children with infectious mononucleosis induced by Epstein-Barr virus / 中国基层医药

Objective:To investigate the relationship between the peak load of Epstein-Barr virus (EPV) and live function damage in children with infectious mononucleosis caused by EPV.Methods:Eighty children with infectious mononucleosis caused by EPV who received treatment in Pingxiang People's Hospital from January 2018 to December 2021 were included in this study. Five mL of venous blood was taken from each child for detecting the peak load of EBV-DNA and liver function indicators. These children were divided into a low-load group ( n = 25, EBV-DNA load < 10 4 copies/mL), a medium-load group ( n = 34, EBV-DNA load of 10 4-10 5 copies/mL), and a high-load group ( n = 21, EBV-DNA load > 10 5 copies/mL) according to the peak EBV-DNA load. The relationships between different peak loads of EBV-DNA and live function, age, and sex were analyzed. Results:The rate of liver dysfunction in the high-load group [85.71% (18/21)] was significantly higher than [38.24% (13/34)] in the medium-load group and [20.00% (5/25)] in the low-load group ( χ2 = 11.90, 19.71, P = 0.001, P < 0.001). Alanine aminotransferase and aspartate aminotransferase levels in the high-load group were (156.24 ± 13.21) U/L and (171.69 ± 13.49) U/L, respectively, which were significantly higher than (125.89 ± 10.54) U/L and (143.26 ± 10.29) U/L in the medium-load group and (89.64 ± 6.75) U/L and (64.89 ± 5.74) U/L] in the low-load group (all P < 0.001). There was no significant difference in the peak load of EBV-DNA between children of different ages and between children of different sexes (both P > 0.05). Conclusion:Children with infectious mononucleosis caused by EPV have a high EBV-DNA peak load. A higher peak load of EVB-DNA indicates a higher risk of liver function damage. More attention should be paid in clinical practice. Effective diagnosis and treatment should be performed in time to control the patient's condition as early as possible.

Diagnostic and prognostic values of the ratio of red blood cell distribution width to platelet count for hepatitis B and liver cirrhosis / 中国基层医药

Objective:To analyze the diagnostic and prognostic values of the red blood cell distribution width-to-platelet count ratio (RPR) for hepatitis B and liver cirrhosis.Methods:The clinical data of 80 patients with hepatitis B and liver cirrhosis who were diagnosed and treated in Yiwu Central Hospital from June 2020 to August 2021 were retrospectively analyzed. These patients were included in the hepatitis B and liver cirrhosis group. They were subdivided into survival ( n = 69) and death ( n = 11) groups according to their prognosis outcomes. Eighty patients with chronic hepatitis B were included in the chronic hepatitis B group. Eighty healthy controls who concurrently underwent physical examination were included in the control group. The diagnostic and prognostic values of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on four factors (FIB-4) for hepatitis B and liver cirrhosis were analyzed. Results:Red blood cell distribution width, alanine transaminase, and aspartate transaminase in the hepatitis B and liver cirrhosis group and chronic hepatitis B group were significantly higher compared with the control group (all P < 0.05). Platelet count in the hepatitis B and liver cirrhosis group and chronic hepatitis B group was significantly lower than that in the control group (both P < 0.05). Red blood cell distribution width in the hepatitis B and liver cirrhosis group was significantly higher than that in the chronic hepatitis B group [(18.25 ± 3.28)% vs. (14.67 ± 2.15)%, t = 8.16, P < 0.05]. Platelet count, alanine transaminase, and aspartate transaminase levels in the hepatitis B and liver cirrhosis group were (78.47 ± 11.43) × 10 9/L, (49.48 ± 6.85) U/L, (45.86 ± 6.28) U/L, respectively, which were significantly lower than (133.36 ± 18.42) × 10 9/L, (128.36 ± 15.40) U/L, (98.67 ± 14.41) U/L in the chronic hepatitis B group ( t = -22.65, -41.86, -30.05, all P < 0.05). PRP, APRI, and FIB-4 in the hepatitis B and liver cirrhosis group were (0.23 ± 0.05), (1.85 ± 0.44), (4.25 ± 0.81) respectively, which were significantly higher than (0.11 ± 0.02), (1.46 ± 0.33), (3.38 ± 0.63) in the chronic hepatitis B group ( t = 19.93, 6.34, 7.58, all P < 0.001). The RPR, APRI, and FIB-4 in the death group were (0.25 ± 0.08), (1.97 ± 0.48), (4.52 ± 1.31), respectively, which were significantly higher than (0.18 ± 0.05), (1.68 ± 0.40), (3.69 ± 1.21) in the survival group ( t = 3.94, 2.17, 2.09, all P < 0.05). The receiver operating characteristic curve revealed that PRP has an extremely high value in diagnosing hepatitis B and liver cirrhosis and predicting the death of patients with hepatitis B and liver cirrhosis. Conclusion:RPR has an extremely high value in diagnosing hepatitis B and liver cirrhosis and predicting the prognosis of this disease.

Relationship between interleukin-1β and silicosis development / 中国基层医药

Silicosis is a diffuse pulmonary fibrosis disease caused by occupational exposure to silica, which is one of the occupational diseases with high incidence in developing countries. Up to now, there is no definite drug to relieve or reverse the lung injury caused by silicosis, so it is very important to prevent, diagnose and treat pulmonary fibrosis as soon as possible. Studies have shown that a chronic inflammatory environment contributes to pulmonary fibrosis to a certain extent. Interleukin-1β is a cytokine that increases the number of inflammatory factors in the microenvironment in the immune response and plays a key role in inflammatory reaction. Therefore, the release of interleukin-1β is of great significance in the pathogenesis of silicosis. This paper aims to systematically expound the development course of silicosis, the signal pathway of interleukin-1β production, and the relationship between them.

Prognostic value of AST/ALT ratio combined with APTT regimen in NVAF patients receiving rivaroxaban anticoagulant therapy / 国际生物医学工程杂志

Objective:To investigate the prognostic value of the ratio of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) combined with activated partial thromboplastin time (APTT) in elderly patients with non-valvular atrial fibrillation (NVAF) treated with rivaroxaban.Methods:One hundred and twenty-two elderly patients with NVAF who were anticoagulated with rivaroxaban from June 2020 to June 2021 in the Third Central Hospital of Tianjin were enrolled and divided into four groups based on the median method. The patients in the Q1 group ( n = 32) have low AST/ALT/low APTT. The patients in the Q2 group ( n = 27) have low AST/ALT/high APTT. The patients in the Q3 group ( n = 29) have high AST/ALT/low APTT. The patients in the Q4 group ( n = 34) have high AST/ALT/high APTT. The efficacy endpoint events, and safety endpoint events were analyzed in the four groups, and univariate and multivariate Cox regression analyses were performed for the composite endpoint events. Results:The effectiveness endpoint events were mainly cardiovascular deaths, the number of which in the Q1 to Q4 groups was 0 (0), 1 (3.70%), 4 (13.79%), and 5 (14.71%), respectively. The safety endpoint events were mainly non-major bleeding events, the number of which in the Q1 to Q4 groups was 5 (15.62%), 2 (7.41%), 6 (20.69%), and 5 (14.71%), respectively. Compared to the Q1 group, the Q4 group had an increased risk of composite endpoint events after incorporating traditional risk factor correction ( HR: 3.851, 95% CI: 1.167 to 12.704). Conclusions:AST/ALT ratio combined with APTT can provide risk stratification for distant bleeding and cardiovascular adverse events in elderly NVAF patients treated with rivaroxaban anticoagulation and has some predictive value for their prognosis.

Value of the combined use of aminotransferase-to-platelet ratio index and total bile acid for predicting parenteral nutrition-associated cholestasis in preterm infants with gestational age <34 weeks / 中国当代儿科杂志

OBJECTIVES@#To explore the value of the combined use of aspartate aminotransferase-to-platelet ratio index (APRI) and total bile acid (TBA) for predicting parenteral nutrition-associated cholestasis (PNAC) in preterm infants with gestational age <34 weeks.@*METHODS@#A retrospective analysis was performed on medical data of 270 preterm infants born at <34 weeks of gestation who received parenteral nutrition (PN) during hospitalization in the First Affiliated Hospital of Wannan Medical College from January 2019 to September 2022, including 128 infants with PNAC and 142 infants without PNAC. The medical data between the two groups were compared, and predictive factors for the development of PNAC were explored through multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to evaluate the value of APRI alone, TBA alone, and the combination of both for predicting PNAC.@*RESULTS@#TBA levels in the PNAC group after 1, 2, and 3 weeks of PN were higher than those in the non-PNAC group (P<0.05). APRI in the PNAC group after 2 and 3 weeks of PN was higher than that in the non-PNAC group (P<0.05). Multivariate logistic regression analysis showed that elevated APRI and TBA after 2 weeks of PN were predictive factors for PNAC in preterm infants (P<0.05). ROC curve analysis showed that the sensitivity, specificity, and area under the curve (AUC) for predicting PNAC by combining APRI and TBA after 2 weeks of PN were 0.703, 0.803, and 0.806, respectively. The AUC for predicting PNAC by combining APRI and TBA was higher than that of APRI or TBA alone (P<0.05).@*CONCLUSIONS@#After 2 weeks of PN, the value of combining APRI and TBA for predicting PNAC is high in preterm infants with gestational age <34 weeks.