N-acetyl-p-aminophenol （APAP） is an antipyretic analgesic commonly used in clinical practice， and APAP overdose can cause severe liver injury and even death. In recent years， the incidence rate of APAP-induced liver injury （AILI） tends to increase， and it has become the second most common cause of liver transplantation worldwide. Autophagy is a highly conserved catabolic process that removes unwanted cytosolic proteins and organelles through lysosomal degradation to achieve the metabolic needs of cells themselves and the renewal of organelles. A large number of studies have shown that autophagy plays a key role in the pathophysiology of AILI， involving the mechanisms such as APAP protein conjugates， oxidative stress， JNK activation， mitochondrial dysfunction， inflammatory response and apoptosis. This article elaborates on the biological mechanism of autophagy in AILI， in order to provide a theoretical basis for the treatment of AILI and the development of autophagy regulators.

The incidence rate of drug-induced liver injury （DILI） is increasing year by year with unknown mechanisms， and the treatment methods for DILI mainly include drugs， liver support systems， and liver transplantation， all of which have certain limitations. Therefore， the search for safer and more effective treatment methods has become a research hotspot at present. Studies have shown that mesenchymal stem cells and their exosomes can alleviate liver injury by reducing liver inflammation， promoting hepatocyte proliferation and regeneration， inhibiting the apoptosis of hepatocytes， improving oxidative stress， and regulating immunity. This article briefly reviews the role of mesenchymal stem cells and their exosomes in the treatment of DILI， so as to provide a reference for further research.

Autoimmune hepatitis(AIH)is a type of chronic hepatitis caused by the attack of hepatocytes by the autoimmune system,and with the prolongation of disease course,it may gradually progress to liver cirrhosis and even hepatocellular carcinoma.Although great achievements have been made in the understanding and treatment of AIH,its etiology and pathogenesis still remain unclear.T cells play a crucial role in the development and progression of AIH,and by focusing on follicular helper T cells,this article elaborates on the research advances in follicular helper T cells in AIH,in order to provide new ideas and strategies for the clinical treatment of AIH.

Autoimmune hepatitis （AIH） is a type of chronic hepatitis caused by the autoimmune system attacking hepatocytes， and its chronic progression may lead to liver cirrhosis and even hepatocellular carcinoma. Currently， pharmacotherapy and liver transplantation are the main treatment methods for AIH， but both methods have their own limitations， which limits the clinical benefits of patients. Therefore， it is a critical issue to search for new therapeutic agents and methods. Recent studies have shown that mesenchymal stem cells （MSC） and their exosomes can improve the symptoms of patients with AIH by suppressing inflammatory response， enhancing the regeneration of hepatocytes， and regulating the immune system and thus have wide application prospects in the treatment of AIH. By summarizing related articles， this article reviews the possible mechanisms and application of MSC and their exosomes in the treatment of AIH， in order to provide new ideas for the clinical treatment of AIH.

Objective:To explore the clinical characteristics and genetics of a Chinese patient with Gitelman syndrome (GS) and improve the awareness and diagnosis of GS among clinicians.Methods:Retrospectively analyzed the GS patient's clinical feature, laboratory examination, diagnosis, treatment and literature review admitted to Hebei General Hospital in September 2022.Results:A twelve-year-old boy was admitted to our department due to weakness of lower limbs. Laboratory tests after admission showed hypokalemia, hypomagnesemia, hypocalcemia and metabolic alkalosis. Genetic testing showed tow compound heterozygous mutations in the SLC12A3 gene (c.1456G>A and c.634G>A), which ultimately diagnosed as GS. The patient is on the mend and allowed to leave the hospital after treated by potassium supplement.Conclusion:The rate of leak diagnosis is high. Genetic testing should be undergo earlier if the patients suspected GS.

Programmed death-1 and programmed death-ligand 1(PD-1/PD-L1)are regulatory immune checkpoint molecules that inhibit T cell activation and,therefore,play an important role in tumor immunotherapy.In recent years,increasing numbers of targeted therapeutic agents have been developed,but single immune checkpoint blockers cannot completely inhibit tumor occurrence,and tumor escape sporadically occurs.Consequently,combination therapy of targeted drugs is considered a useful method to inhibit tumorigenesis and tumor development.T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif(ITIM)domain(TIGIT)is an inhibitory type 1 poliovirus receptor that has recently been a hotspot of targeted drug therapy research.It has been shown that the combination therapy of TIGIT plus PD-1/PD-L1 can reduce tumor escape and inhibit tumorigenesis more effectively.Therefore,this review summarizes and discusses the progress on the dual blockade of TIGIT and PD-1/PD-L1 pathways in tumor immunotherapy to provide a theoretical basis for tumor im-munotherapy.

Objective:To explore the application of OTSU-based self-attenuation correction PET (sacPET) reconstruction technology in 18F-florbetapir (AV45) imaging. Methods:From November 2018 to December 2019, 7 confirmed Alzheimer′s disease (AD) patients (4 males, 3 females, age (69.6±4.5)years) and 3 healthy controls (HC; 1 male, 2 females, age (68.0±4.6) years) were recruited prospectively for 18F-AV45 PET imaging in the First Affiliated Hospital of Sun Yat-Sen University. Original data collected by PET acquisition was processed with sacPET reconstruction and then compared with standard PET images by visual analysis and semi-quantitative analysis. Fisher exact test, Kappa test and Pearson correlation analysis were used to analyze data. Results:In HC group and AD group, the radioactive distribution showed by sacPET images and that by standard PET images were similar, and the contrast of gray-white matter in sacPET images was weaker than that in standard PET images. Moreover, the positive uptake area of the cortex in the AD group was smaller than that in standard PET images. Visual analysis showed 19 positive regions in sacPET images and 22 in standard PET images, with no statistical difference of positive rates of the sub-regions in the cortex between the two PET images (all P>0.05), and the overall consistency of 88.00% (44/50; Kappa=0.75 (95% CI: 0.57-0.94), P<0.05). Semi-quantitative analysis showed that the standardized uptake value ratio (SUVR) of frontal lobe and cingulate gyrus measured by sacPET was lower than that measured by standard PET (0.93±0.06 vs 0.96±0.06 and 0.99±0.04 vs 1.01±0.04; t values: 5.30 and 5.10, both P<0.01), while SUVR of parietal lobe, temporal lobe and occipital lobe measured by sacPET was higher than that measured by standard PET (0.78±0.08 vs 0.68±0.07, 0.97±0.07 vs 0.91±0.08 and 0.94±0.11 vs 0.71±0.12; t values: 6.27, 7.36 and 16.90, all P<0.01). The overall SUVR of sacPET images was significantly correlated with the standard PET images ( r=0.75, P<0.001). Conclusion:For 18F-AV45 imaging, sacPET reconstruction technology can obtain reliable and effective PET images without CT data, but its accuracy and precision still need to be improved.

Objective:To investigate the effect of self fixing mesh with " Y-shaped" placement in laparoscopic transabdominal preperitoneal repair of female inguinal hernia.Methods:From February 2019 to September 2020, a total of 40 female patients who underwent TAPP (Keyhole method) in Shaanxi Provincial People′s Hospital were researched.Random number table method was used.According to different patch placement methods, the patients were divided into the self fixing mesh with " Y-shaped" placement group (21 cases) and with normal placement group (19 cases). The operative time, placement time, length of stay, Visual Analogue Scale (VAS), postoperative complication were compared between two groups.Results:All 40 patients completed TAPP, and all patients were followed up successfully, with a median follow-up time of 12.5 months.The operation time and patch placement time were (54.9±9.0) min and (10.8±2.5) min in the Y-shaped placement method group and (62.8±11.2) min and (20.3±3.5) min in the conventional placement method group, respectively; the differences between the two groups were statistically significant ( t=2.490, P=0.017; t=.925, P<0.001). There was no statistically significant difference between the two groups in length of stay, VAS score 1 day after surgery and postoperative complications(all P>0.05). Conclusion:In laparoscopic female inguinal hernia repair (keyhole method), the " Y" shape placement method can effectively shorten the time of self fixing patch placement, thus shorten the operation time, and does not increase the risk of complications.

Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter in the adult central nervous system (CNS), however, it causes excitation in the immature CNS neurons. The shift from GABA-induced depolarization to hyperpolarization in postnatal brain is primarily due to progressive decrease in the expression of the Na-K-2Cl symporter 1 (NKCC1) and increased expression of the K-Cl cotransporter 2 (KCC2). Unlike CNS neurons, both immature and mature neurons in the enteric nervous system (ENS) are depolarized by GABA. Molecular mechanisms by which GABA excites ENS neurons are unclear. It is understood, however, that the excitatory action depends on elevated intraneuronal Cl. We aimed to test a hypothesis that high intracellular Cl in ENS neurons is maintained by activity of the NKCCs. We found that NKCC2 immunoreactivity (IR) was expressed in the ENS of the rat colon on postnatal day 1 (P1). The expression level of NKCC2 continuously increased and reached a steady high level on P14 and maintained at that level in adulthood. NKCC1 IR appeared in ENS on P14 and maintained through adulthood. KCC2 IR was not detectable in the ENS in any of the developmental stages. Both NKCC1 IR and NKCC2 IR were co-expressed with GABA receptors in ENS neurons. Exogenous GABA (1 mmol/L) caused membrane depolarization in the ENS neurons. The reversal potential of GABA-induced depolarization was about -16 mV. Blockade of NKCC by bumetanide (50 μmol/L) or furosemide (300 μmol/L) suppressed the depolarizing responses to GABA. Bumetanide (50 μmol/L) shifted the reversal potential of GABA-induced depolarization in the hyperpolarizing direction. Neither the KCC blocker DIOA (20 μmol/L) nor the Cl/HCO exchanger inhibitor DIDS (200 μmol/L) suppressed GABA-evoked depolarization. The results suggest that ENS neurons continuously express NKCC2 since P1 and NKCC1 since P14, which contribute to the accumulation of Cl in ENS neurons and GABA-evoked depolarization in neonate and adult ENS neurons. These results provide the first direct evidence for the contribution of both NKCC2 and NKCC1 to the GABA-mediated depolarization.
Animals ; Bumetanide ; Neurons ; Rats ; Receptors, GABA-A ; Symporters ; gamma-Aminobutyric Acid

Objective:To analyze the disadvantages of " paper-centric" in science and technology evaluation, explore how to establish a new evaluation model of scientific and technological innovation in academic universities in China on the premise of breaking the " paper-centric" orientation.Methods:Analyze problems and disadvantages of the " paper-centric" orientation in the evaluation of science and technology at academic universities in China, take account into the in-depth interpretation of key policies of breaking away from " paper-centric" in recent years, and finally make proposal for the establishment of evaluation system and mode of scientific and technological innovation in the future.Results:There are many pitfalls in the " paper-centric" orientation in the evaluation of science and technology in academic universities in China, thus, it is urgent to establish a new evaluation mode of scientific and technological innovation.Conclusions:Based on the current domestic and international context, academic universities in China should deploy the strategy of scientific and technological innovation in advance, break the " paper-centric" orientation, and establish a new evaluation system and mode of science and technology that proactively match the national strategy and the development requirement.