Objective To investigate the role and mechanism of suramin(Sur)in acetaminophen(APAP)-induced acute liver injury in mice.Methods 8-10 weeks old C57BL/6J mice were randomly divided into the APAP group and APAP+Sur group(20 mg/kg suramin was injected 1 h before).After 18 hrs of fasting,400 mg/kg APAP was injected intraperitoneally to establish a mouse model of acute liver failure and the survival rate was recorded.An acute liver injury model of mice was established via intraperitoneal injection of 300 mg/kg APAP(other conditions remained unchanged).A control group was also established,with liver tissues and serum collected at 0,2,and 12 hours post-APAP treatment.ELISA and CBA techniques were adopted to detect the release of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)in serum and the secretion of inflammatory factors.H&E staining and immunohistochemistry were used to detect liver tissue necrosis and inflammatory cell infiltration.DCFA-DH and ELISA techniques were used to detect the levels of reactive oxygen species(ROS),malondialdehyde(MDA)and glutathione(GSH)in liver tissues.Western blotting was employed to assess the activation of the JNK signaling pathway in liver tissues.Results Suramin treatment improved the survival rate of APAP-induced mice,reduced the release of transaminases and inflammatory factors in serum,and alleviated APAP-induced liver cell necrosis and inflammatory cell infiltration in the liver.Suramin treatment delayed APAP-induced GSH depletion in the liver,reduced MDA and ROS levels,and inhibited JNK pathway activation.Conclusion This study has confirmed the protective effect of suramin against acetaminophen-induced acute liver injury in mice.The mechanism is potentially related to oxidative stress and inflammation.

Objective:To evaluate the efficacy and safety of Xiao′er Huangjin Zhike Granules in the treatment of cough caused by acute bronchitis in children, which is defined in TCM terms as a syndrome of phlegm-heat obstructing the lung.Methods:This was a block-randomized, double-blind, placebo-controlled, multicenter clinical trial.From January 2022 to September 2023, 359 children aged 3 to 7 years old diagnosed as acute bronchitis (lung-obstructing phlegm-heat syndrome) were enrolled from 21 participating hospitals and randomly assigned to the experimental group and placebo group in a 3︰1 ratio, and respectively treated with Xiao′er Huangjin Zhike Granules and its matching placebo.Cough resolution/general resolution rate after 7 days of treatment was used as the primary efficacy outcome for both groups.Results:(1)On the seventh day of treatment, the rate of cough disappearance/basically disappearance in the experimental group and placebo group were 73.95% and 57.61% retrospectively, which had statistically significance ( P=0.001).(2)After 7 days of treatment, the median duration of cough disappearance/basic disappearance were 5 days and 6 days in the two groups , with a statistically significant difference ( P=0.006).The area under the curve of cough symptom severity time was 7.20 ± 3.79 in the experimental group and 8.20±4.42 in the placebo group.The difference between the two groups was statistically significant ( P=0.039).(3) After 7 days of treatment, the difference between TCM syndrome score and baseline was -16.0 (-20.0, -15.0) points in the experimental group and -15.0 (-18.0, -12.0) points in the placebo group, with significant difference between the two groups ( P=0.004).In the experimental group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 49.04%, 28.35%, 16.48% and 6.13% severally; and in the placebo group, the clinical control rate, the markedly effective rate, the effective rate and the ineffective rate were 38.04%, 26.09%, 29.35%, and 6.52% separately, which had statistically significant ( P=0.014).(4) There was no significant difference in the incidence of adverse events or adverse reactions during the trial between both groups.Moreover, while adverse reactions in the form of vomiting and diarrhea were occasionally reported, no serious drug-related adverse event or adverse reaction was reported.(5)The tested drug provided good treatment compliance, showing no statistically significant difference from the placebo in terms of compliance rate. Conclusions:Based on the above findings, it can be concluded that Xiao′er Huangjin Zhike Granules provides good safety, efficacy, and treatment compliance in the treatment of cough caused by acute bronchitis, and lung-obstructing phlegm-heat syndrome, in children.

Objective By knocking down the expression of fibroblast growth factors 21(FGF21)in adipose liver cells,to observe lipid metabolism and to explore the molecular mechanism of FGF21 regulating lipid metabolism in liver cells.Methods By interfering with lentivirus transfection through FGF21,the expression of FGF21 was reduced in HepG2 cells.HepG2 cells were transfected with an empty vector as a control,and were respectively referred to as interference group and control group.Both groups were stimulated with palmitic acid oleic acid to construct non-alcoholic fatty liver disease(NAFLD)cell model.The expression of FGF21 was interfered by lentivirus vector,oil red O staining and spectrophotometric value were measured to observe the lipid deposition in cells.Use Western blot method to detect the changes of suppressor of cytokine signaling 3(SOCS3),JAK2,and STAT3 proteins in fatty liver cells.Results Oil red O staining and absorbance values showed that compared with control group,interference group significantly reduced the lipid droplet content in liver cells;Western blot results showed that the expression levels of suppressor of cytokine signaling 3(SOCS3),Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),and STAT3 protein were significantly increased in interference group of liver cells.Conclusion In the fatty liver cell model,knocking down FGF21 can improve lipid deposition through liver cells.The mechanism may be through increasing the SOCS3/JAK/STAT pathway,but the specific mechanism of action needs further in-depth research in the future.

This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Grooming,as an evolutionarily conserved repetitive behavior,is common in various animals,including humans,and serves essential functions including,but not limited to,hygiene maintenance,thermoregulation,de-arousal,stress reduction,and social behaviors.In rodents,grooming involves a patterned and sequenced structure,known as the syntactic chain with four phases that comprise repeated stereotyped movements happening in a cephalocaudal progression style,beginning from the nose to the face,to the head,and finally ending with body licking.The context-dependent occurrence of grooming behavior indicates its adaptive significance.This review briefly summarizes the neural substrates responsible for rodent grooming behavior and explores its relevance in rodent models of neuropsychiatric disorders and neurodegenerative diseases with aberrant grooming phenotypes.We further emphasize the utility of rodent grooming as a reliable measure of repetitive behavior in neuropsychiatric models,holding promise for translational psychiatry.Herein,we mainly focus on rodent self-grooming.Allogrooming(grooming being applied on one animal by its conspecifics via licking or carefully nibbling)and heterogrooming(a form of grooming behavior directing towards another animal,which occurs in other contexts,such as maternal,sexual,aggressive,or social behaviors)are not covered due to space constraints.

Objective:To investigate the expression of anaplastic lymphoma kinase (ALK), tropomyosin receptor kinase (TRK), and recombinant C-Ros oncogene 1, receptor tyrosine kinase (ROS1) in Spitz tumors, and to analyze their associations with clinical and histopathological features of Spitz tumors.Methods:Clinical and histopathological characteristics, as well as follow-up data, were collected from patients with Spitz tumors at Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences from January 2017 to August 2023, and retrospectively analyzed. Immunohistochemical staining for ALK, pan-TRK, and ROS1 was performed on skin tissues, and associations between the expression of these kinase proteins and clinicopathological features were analyzed.Results:A total of 57 patients with Spitz tumors were collected, including 36 females and 21 males. Immunohistochemical staining showed that 30 (52.6%) patients were positive for ALK, 4 (7.0%) were positive for ROS1, only 2 (3.5%) were positive for TRK, and 21 (36.8%) were negative for the three kinase proteins. Among the 30 ALK-positive patients, the median age was 9.5 years, 21 (70.0%) were females, and 15 (50.0%) presented with lesions on the face, which mainly manifested as papules or nodules; histologically, 29 (96.7%) patients had hypopigmented tumors with an exophytic growth pattern, and the tumor cells were mainly large and long spindle cells arranged in long cord-like, plexiform or fascicular patterns. Among the 4 ROS1-positive patients, there were 3 females and 1 male, presenting with exophytic papules or polyps; histologically, tumor cells were mostly arranged in small nests, without obvious clefts around cell nests. Two TRK-positive patients were both males aged 20 and 50 years respectively, and presented with brown and skin-colored flat papules, respectively; histologically, the tumors were located superficially with a flat base, and tumor cells spread in a pagetoid pattern in the epidermis, with some epithelioid cells and small cell nests. Among the 21 patients negative for the 3 kinase proteins, 9 were males and 12 were females, and they clinically presented with macules, papules and polypoid lesions; histologically, most tumors were located superficially, consisting of a mixture of epithelioid cells and spindle cells, with rare cytological atypia and mitotic figures, and 2 cases showed mild tissue structural and cellular atypia. Fifty-seven patients were followed up for 2 - 83.3 months, with a median follow-up of 19.2 months. Only 1 ALK-positive child experienced a recurrence, and no recurrence or lymph node metastasis was observed in the other cases.Conclusions:Among the three kinase proteins, ALK showed the highest positive rate in Spitz tumors in this study, while TRK- and ROS1-positive cases were sporadic. Histopathologically, ALK-positive Spitz tumor cells were mainly long spindle cells arranged in long cord-like or plexiform patterns, while TRK- and ROS1-positive Spitz tumors tended to have small cell nests. Both the kinase protein-positive and -negative Spitz tumors mostly had a good prognosis.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

The comparison between traditional Chinese medicine Jinzhen oral liquid (JZOL) and Western medicine in treating children with acute bronchitis (AB) showed encouraging outcomes. This trial evaluated the efficacy and safety of the JZOL for improving cough and expectoration in children with AB. 480 children were randomly assigned to take JZOL or ambroxol hydrochloride and clenbuterol hydrochloride oral solution for 7 days. The primary outcome was time-to-cough resolution. The median time-to-cough resolution in both groups was 5.0 days and the antitussive onset median time was only 1 day. This randomized controlled trial showed that JZOL was not inferior to cough suppressant and phlegm resolving western medicine in treating cough and sputum and could comprehensively treat respiratory and systemic discomfort symptoms. Combined with clinical trials, the mechanism of JZOL against AB was uncovered by network target analysis, it was found that the pathways in TRP channels like IL-1β/IL1R/TRPV1/TRPA1, NGF/TrkA/TRPV1/TRPA1, and PGE2/EP/PKA/TRPV1/TRPA1 might play important roles. Animal experiments further confirmed that inflammation and the immune regulatory effect of JZOL in the treatment of AB were of vital importance and TRP channels were the key mechanism of action.

Objective:To study the morphology of hemophagocytosis (HPC) in bone marrow smears of patients with infection-associated hemophagocytic lymphohistiocytosis (IAHLH), and further analyse if there were differences in the clinical and laboratory features, the cytokines level and prognosisMethods:24 patients newly diagnosed with IAHLH from 2016-Dec-1 to 2021-Dec-31 in Beijing Friendship Hospital were included as study group, and 20 patients with infectious disease as non-HLH control group. In IAHLH group, mean age was 34±13 years, including 17(71%) males and7(29%) females. In Non-HLH group, mean agewas 43±16 years, including 14 (70%) males and6 (30%) females. Depending on re-checking phagocytic cell type on the initial bone marrow smear, the HPCs were divided into HPC-1, phagocytizing non-nucleated cells (mature erythrocyte or platelets), and HPC-2, phagocytizing nucleated cells. The differences in clinical presentations covered in HLH-2004 criteria, cytokines value(IL-6, IL-10, IL-18, IFN-γ) recommended in HLH-2022-China guideline, and the mortality within 1 year of diagnosis, were compared between IAHLH and non-HLH groups, between patients with or without HPC, and between patients with HPC-2 or only with HPC-1. For categorical variables, two groups were compared with the use of either the chi-square test or Fisher′s exact test. For non-normal distribution continuous variables, the difference between two groups variation was performed by using Mann-Whitney U test, and for normal distribution continuous variables, the difference was by the Independent Samples t-test.Results:The positive rates of fever, hepatomegaly and splenomegalyand the motrtality in IAHLH were 100% (24/24), 63% (15/24), 92% (22/24) and 46% (11/24), respectivelyin non-HLH were 55%(11/20),0(0/20),25% (5/20),0(0/20),and the differences between two groups were all statistically significant( P<0.01), but thedifferences between groups with and without HPC and between IAHLH patients with HPC-2 or only with HPC-1 were no statistically significanlly, ( P>0.05).In IAHLH group, IFN-γ in patients with HPC-2 was 400(246, 532)ng/L, significantly higher than 146(38, 180)ng/L in patients only with HPC-1 [ P=0.02, 95% CI was 233(75.8 to 397)], andthe other test parameters and cytokines level showed no obvious differences ( P>0.05).

Objective: To explore the pathogenic genes in a Chinese family affected by nonsyndromic tooth agenesis so as to study the pathogenesis of oligodontia. Methods : Hospital ethical approval and informed consent of the patients and family members were obtained. Clinical data of the proband and close family members were collected, peripheral venous blood was collected, and DNA was extracted. Gene sequencing was performed through whole-exome sequencing, and then the screened pathogenic genes were verified by Sanger sequencing. The three-dimensional structure of the mutant proteins was analyzed and compared with the wild-type using bioinformatics tools. Results: The two patients with congenital majority tooth loss in this family were cousins, and there were no other patients with congenital majority tooth loss in the family. Besides congenital multiple tooth loss, the two patients had no obvious hair abnormalities, finger/toe abnormalities, sweating abnormalities or other abnormal manifestations of ectodermal tissue. We found a mutant gene that in this family by carrying out gene sequencing of the patients and their close family members. A novel EDA (ectodysplasin A) missense mutation c.983C>T (p. Pro328Leu) was identified, which changed the encoded amino acid from proline (Pro) to leucine (Leu). Analysis of the mutation site showed that the site was highly conserved, and three-dimensional structure modeling also found that it changed the structure of EDA. Conclusion A novel EDA missense variant (c.983C>T, p.Pro328Leu) was first identified in a Chinese family with nonsyndromic tooth agenesis, extending the mutation spectrum of the EDA gene.