ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked （DDX3X） in immune-mediated liver injury （ILI）， and to clarify its mechanism by regulating endoplasmic reticulum stress （ERS）-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A （ConA） via the caudal vein to establish a model of ILI， PBS （control group） and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice （DDX3X^ΔHep and DDX3X-flox mice （DDX3X^fl/fl）， respectively.. The log-rank survival analysis， measurement of the serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT）， and HE staining of liver tissue were performed to assess liver injury， and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 （GRP78）， CCAAT/enhancer-binding protein homologous protein （CHOP）， and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid （4-PBA， 100 mg/kg） was performed to inhibit ERS. Serum samples （n=30） and liver tissue samples （n=6） were collected from healthy controls， chronic hepatitis B （CHB） patients， and hepatitis B virus-associated liver failure （HBV-LF） patients； ELISA was used to measure the serum level of DDX3X， and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice， the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury （P<0.05）， and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% （compared with 20% in the DDX3X^fl/fl group）， with significant reductions in the serum levels of ALT and AST （P<0.000 1） and the expression levels of the ERS markers GRP78 and CHOP （P<0.05）. After ERS was inhibited by 4-PBA， there was alleviation of liver injury （with reductions in ALT and AST， P <0.001） and a reduction in DDX3X expression （P<0.01）. The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls （all P<0.01）， and there was a significant increase in the serum level of DDX3X in HBV-LF patients （P<0.000 1）. ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway （GRP78/CHOP）， and its expression is associated with the progression of hepatitis B. Therefore， it can be used as a potential therapeutic target.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure （CHF）. METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery. Modeled rats were divided into model group， Qiangxin decoction low-dose and high-dose groups （12.25， 24.50 g/kg， calculated by crude drug）， and chemical medicine group （Sacubitril valsartan sodium tablets， 10.42 mg/kg）， with 10 rats in each group； control group was set up without treatment. Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days. After the last medication， the contents of N-terminal pro-brain natriuretic peptide （NT-proBNP） and adenosine triphosphate （ATP） in serum and phosphatidic acid （PA） and cardiolipin （CL） in myocardial tissue were all detected； the pathological damage and collagen fibrosis of rat myocardial tissue were observed； the apoptosis of myocardial cells was determined； the ultrastructure of myocardial tissue was observed； the protein expressions of mitofusin 1 （Mfn1）， Mfn2， optic atrophy protein 1 （OPA1） and dynamin-related protein 1 （Drp1） were all detected in myocardial tissue. RESULTS Compared with control group，the serum content of NT-proBNP， apoptotic rate of myocardial cells， and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly； serum content of ATP，contents of PA and CL， and relative expressions of Mfn1， Mfn2 and L-OPA1 proteins were all significantly reduced （P＜0.05）. There were abnormal membrane tissue structure in various layers of myocardial tissue， degeneration and necrosis of myocardial cells， and severe fibrosis； the mitochondria were swollen， with reduced or absent cristae， and uneven matrix density. After intervention with Qiangxin decoction， the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats （excluding CL content in the Qiangxin decoction low- dose group） were significantly reversed （P＜0.05）； the pathological damage of myocardial tissue had significantly improved， fibrosis had significantly reduced， mitochondrial morphology tended to be normal， cristae had increased， and matrix density was uniform. CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats， thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis， the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Abstract In April 2021, type Ⅰ vaccine-derived poliovirus (VDPV) was detected from two fecal samples of a male infant with acute flaccid paralysis (AFP) in Zhejiang Province when he was admitted to the Children's Hospital Affiliated to Fudan University in Shanghai, with 12 and 14 nucleotide mutations in the VP1 region, respectively. The case had a history of immunization with three doses of poliovirus vaccines, and grade Ⅲ proximal muscle strength and grade Ⅱ distal muscle strength of the right lower limb. After symptomatic treatment, the activity of the right lower limb and the muscle strength was significantly restored, thus he was discharged. VDPV was not detected from subsequent (the 8th to 12th) fecal samples of the case and fecal samples of close contacts. No similar cases were found in medical institutions in the county, surrounding areas, neighboring villages or towns. Since the case did not exhibit clinical symptoms of poliomyelitis caused by VDPV, poliomyelitis was excluded, and the case was diagnosed with hemophilia type A based on the epidemiological investigation, laboratory tests, and the history of poliomyelitis vaccination. This event involved cross-provincial (municipal) cooperation and was responsed promptly, preventing further spread of the virus. It suggested that the sensitivity of the AFP case surveillance system should be maintained, environmental monitoring methods should be increased, and the poliomyelitis vaccination should be promoted to prevent the spread of the virus.

As a common ophthalmic disease, floaters have a complex etiology. It involves changes in the structure and function of the vitreous body and is closely associated with factors like age and myopia. Vitreous liquefaction and posterior detachment play a crucial role in this regard. Clinically, patients usually experience the floating of dotted or linear black shadows in front of their eyes, and generally, floaters do not cause visual impairment. In the past, due to the limitations of traditional concepts and treatment methods, a conservative observation strategy was often adopted. However, an increasing number of patients have complained that floaters lead to difficulties in driving and reading, which seriously affects their visual quality and mental health. Consequently, the demand for treatment has been growing day by day. The existing treatment options each have their own advantages and disadvantages. The efficacy of drug treatment is limited and remains controversial. Vitrectomy has a definite curative effect, yet it comes with a high risk of complications. YAG laser vitreolysis is relatively safe, but its curative effect is restricted by factors such as the size and location of the opacities. Nanobubble-mediated vitreolysis is still in the research stage and is expected to offer patients safer and more effective treatment in the future. This article reviews the etiology of floaters and the latest progress in its treatment, aiming to deepen clinicians' understanding of floaters, provide a more comprehensive scientific basis for clinical diagnosis and treatment, and promote personalized and precise treatment.

As a common ophthalmic disease, floaters have a complex etiology. It involves changes in the structure and function of the vitreous body and is closely associated with factors like age and myopia. Vitreous liquefaction and posterior detachment play a crucial role in this regard. Clinically, patients usually experience the floating of dotted or linear black shadows in front of their eyes, and generally, floaters do not cause visual impairment. In the past, due to the limitations of traditional concepts and treatment methods, a conservative observation strategy was often adopted. However, an increasing number of patients have complained that floaters lead to difficulties in driving and reading, which seriously affects their visual quality and mental health. Consequently, the demand for treatment has been growing day by day. The existing treatment options each have their own advantages and disadvantages. The efficacy of drug treatment is limited and remains controversial. Vitrectomy has a definite curative effect, yet it comes with a high risk of complications. YAG laser vitreolysis is relatively safe, but its curative effect is restricted by factors such as the size and location of the opacities. Nanobubble-mediated vitreolysis is still in the research stage and is expected to offer patients safer and more effective treatment in the future. This article reviews the etiology of floaters and the latest progress in its treatment, aiming to deepen clinicians' understanding of floaters, provide a more comprehensive scientific basis for clinical diagnosis and treatment, and promote personalized and precise treatment.

OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

[Objective] To conduct serological identification and molecular mechanism study on a ambiguous ABO blood group. [Methods] Standard serological techniques were used for the forward and reverse typing of ABO blood type. ABO gene coding and regulatory regions were analyzed by PCR after DNA extraction. Monoclonal sequencing was used to detect the haplotypes of the DNA sequence, and bioinformatics analysis was applied to predict the possible translation outcomes of the mutated DNA sequence. [Results] The sample’s red blood cells showed mixed field agglutination with anti-A, and the serum agglutinated with B cells, exhibiting serological characteristics of subtype A. Direct sequencing and monoclonal sequencing analysis of the ABO gene confirmed one allele as O02, the other had a c.27delC mutation compared with A102, which could cause the translation sequence to terminate prematurely at the 19th amino acids. Analysis and prediction suggested that the mutation might affect the function of the transferase through mechanisms such as shifting the initiation codon, altering the reading frame and affecting the splice sites. [Conclusion] This case is a rare A subtype caused by the c.27delC variation, and the impact on the glycosyltransferase may involve multiple mechanisms, which require further research and exploration.

Sepsis is a systemic inflammatory response syndrome caused by the invasion of pathogenic microorganisms such as bacteria. In addition to the manifestations of systemic inflammatory response syndrome and primary infection lesions， critical cases often have manifestations of organ hypoperfusion. The morbidity and mortality of sepsis have remained high in recent years， which seriously affect the quality of life of the patients. The pathogenesis of sepsis is complicated， in which uncontrollable inflammation is a key mechanism. The phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway plays a key role in mediating inflammation in sepsis. The available therapies of sepsis mainly include resuscitation， anti-infection， vasoactive drugs， intensive insulin therapy， and organ support， which show limited effects of reducing the mortality. Therefore， finding new therapeutic drugs is a key problem to be solved in the clinical treatment of sepsis. In recent years， studies have shown that traditional Chinese medicine （TCM） can regulate the PI3K/Akt pathway via multiple pathways， multiple effects， and multiple targets to inhibit inflammation and curb the occurrence and development of sepsis， which has gradually become a hot spot in the prevention and treatment of sepsis. Moreover， studies have suggested that TCM has unique advantages in the treatment of sepsis. TCM can regulate the PI3K/Akt signaling pathway to inhibit inflammation， reduce oxidative stress， and control apoptosis in the prevention and treatment of sepsis. Despite the research progress， a systematic review remains to be performed regarding the TCM treatment of sepsis by regulating the PI3K/Akt signaling pathway. After reviewing relevant papers published in recent years， this study systematically summarizes the relationship between PI3K/Akt pathway and sepsis and the role of TCM in the treatment of sepsis， aiming to provide new ideas for the potential treatment of sepsis and the development of new drugs.

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.