ObjectiveTo investigate the inhibitory effects and mechanisms of Xiayuxue Tang （XYXT） on hepatocellular carcinoma cells through the regulation of succinate metabolism and succinylation modification. MethodsXYXT-medicated serum was prepared. The effects of different concentrations of succinate on the proliferation of HepG2 and MHCC97H cells were observed using the cell counting kit-8 （CCK-8） assay， and the experimental concentrations for subsequent tests were determined. Further CCK-8 assays were performed to evaluate the effects of XYXT-medicated serum of different concentrations （5%， 10%， and 15%） on cell proliferation. Flow cytometry， scratch test， and Transwell assay were employed to analyze the effect of 10% XYXT-medicated serum on the cell cycle， migration， invasion， and apoptosis. The changes in succinate metabolism and succinylation modification were examined based on succinate content assays， succinate dehydrogenase （SDH） activity detection， and western blot. The expressions of Yes-associated protein 1 （YAP1） and sirtuin 5 （SIRT5） were detected via Real-time PCR and western blot. Molecular docking was applied to validate the binding between XYXT’s main components and target proteins. ResultsCompared with the control group， 1-2 mmol·L^-¹ succinate significantly promoted HepG2 and MHCC97H cell proliferation （P<0.01）. XYXT-medicated serum （5%， 10%， and 15%） markedly inhibited the proliferation of both cell lines compared with the blank group （P<0.05， P<0.01）. Treatment with 10% XYXT-medicated serum arrested the cell cycle at the stage prior to DNA synthesis （G₀/G₁） （P<0.01）， suppressed migration （P<0.01） and invasion （P<0.05， P<0.01）， and promoted apoptosis of HepG2 and MHCC97H cells （P<0.01）. Co-treatment with XYXT and succinate reversed the inhibitory effects of XYXT on proliferation， migration， and invasion of HepG2 and MHCC97H cells （P<0.05， P<0.01）. The proportion of cells at G₀/G₁ phase decreased （P<0.01）， and the apoptosis rate decreased （P<0.01）. In terms of succinate metabolism， compared with the blank serum group， the 10% XYXT-medicated serum reduced succinate levels of HepG2 and MHCC97H cells （P<0.05， P<0.01）， enhanced SDH activity （P<0.01）， and downregulated succinylation modification. In terms of YAP1/SIRT5 pathway， compared with the blank serum group， the 10% XYXT-medicated serum significantly downregulated the mRNA and protein expressions of YAP1 in HepG2 and MHCC97H cells （P<0.05， P<0.01） while significantly upregulated the mRNA and protein expressions of SIRT5 （P<0.05， P<0.01）. Molecular docking confirmed that there was a good binding ability between YAP1 and SIRT5， as well as between XYXT's main active components and YAP1 and SIRT5. ConclusionXYXT suppresses hepatocellular carcinoma cells by modulating the YAP1/SIRT5 signaling axis to intervene in succinate metabolism and succinylation modification.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

ObjectiveTo evaluate the efficacy and safety of Xiaoji Hufei Formula in protecting children with close contact exposure to influenza， and to provide reference and evidence-based support for better clinical prevention and treatment of influenza in children. MethodsA multicenter， prospective， non-randomized， parallel， controlled trial was conducted from October 2021 to May 2022 in five hospitals， including Dongfang Hospital of Beijing University of Chinese Medicine. Confirmed influenza cases and influenza-like illness （ILI） cases were collected， and eligible children with close contact exposure to these cases were recruited in the outpatient clinics. According to whether the enrolled close contacts were willing to take Xiaoji Hufei formula for influenza prevention， they were assigned to the observation group （108 cases） or the control group （108 cases）. Follow-up visits were conducted on days 7 and 14 after enrollment. The primary outcomes were the incidence of ILI and the rate of laboratory-confirmed influenza. Secondary outcomes included traditional Chinese medicine （TCM） symptom score scale for influenza， influenza-related emergency （outpatient） visit rate， influenza hospitalization rate， and time to onset after exposure to influenza cases. ResultsA total of 216 participants were enrolled， with 108 in the observation group and 108 in the control group. Primary outcomes： （1） Incidence of ILI： The incidence was 12.0% （13/108） in the observation group and 23.1% （25/108） in the control group， with the observation group showing a significantly lower incidence （χ²=4.6， P<0.05）. （2） Influenza confirmation rate： 3.7% （4/108） in the observation group and 4.6% （5/108） in the control group， with no statistically significant difference. Secondary outcomes： （1） TCM symptom score scale： after onset， nasal congestion and runny nose scores differed significantly between the two groups （P<0.05）， while other symptoms such as fever， sore throat， and cough showed no significant differences. （2） Influenza-related emergency （outpatient） visit rate： 84.6% （11 cases） in the observation group and 96.0% （24 cases） in the control group， with no significant difference. （3） Time to onset after exposure： The median onset time after exposure to index patients was 7 days in the observation group and 4 days in the control group， with a statistically significant difference （P<0.05）. ConclusionIn previously healthy children exposed to infectious influenza cases under unprotected conditions， Xiaoji Hufei formula prophylaxis significantly reduced the incidence of ILI. Xiaoji Hufei Formula can be recommended as a specific preventive prescription for influenza in children.

Objective To evaluates the impact of early application of neuromuscular electrical stimulation(NMES)on muscle strength,clinical outcomes,and long-term quality of life improvements in patients with severe acute pancreatitis(SAP)complicated with acute respiratory distress syndrome(ARDS).Methods A total of 75 patients diagnosed with SAP and ARDS admitted in Department of Critical Care Medicine of our hospital from September 2022 to August 2023 were recruited and then randomly divided into NMES group(n=37)and control group(n=38).After 16 patients were excluded,including 8 died during treatment,3 discharged and 5 received palliative care,there were finally 29 patients in the NMES group and 30 in the control group.Within 48 h after ICU admission,the NMES group received NMES 1 h per day,for 7 d in addition to standard rehabilitation intervention.While,the control group were given conventional interventions for rehabilitation.Assessments at baseline and post-treatment included the incidence of ICU-acquired weakness(ICU-AW),Medical Research Council(MRC)score,duration of mechanical ventilation,lengths of ICU and total hospital stays,and activity,thickness and thickening fraction of the diaphragm.Mortality rates and Barthel index(BI)for self-care ability in 1,3 and 6 months after discharge were recorded for follow-up assessments.Results The NMES group had significantly lower incidence of ICU-AW(P＜0.05),higher upper and lower limb MRC scores and overall MRC score at ICU discharge(P＜0.05),shorter durations of mechanical ventilation,ICU stay,and total hospital stay when compared with the control group(P＜0.05).There was no statistical difference in the BI at 1 month post-discharge between the 2 groups,but the indexes at 3 and 6 months were notably higher in the NMES group than the control group(P＜0.05).No obvious differences were observed between the 2 groups in terms of diaphragm activity,thickness,or thickening scores at enrollment,ICU discharge,or hospital discharge,nor in mortality rates at 1,3,and 6 months after discharge.Conclusion Combined NMES and early rehabilitation therapy can improve muscle strength and reduce length of hospital stay in SAP patients complicated with ARDS,and may enhance long-term quality of life.However,it does not significantly affect diaphragm function or mortality rates.

Objective:To investigate the application effect of the thinking pattern of "Six Thinking Hats" combined with case-based learning-reference induced self-education (CBL-RISE) teaching in clinical practice teaching of thoracic surgery.Methods:A total of 122 interns who received clinical practice teaching in Department of Thoracic Surgery in the Second Xiangya Hospital of Central South University were selected as subjects, and according to the admission order, they were divided into control group (61 interns receiving routine teaching) and observation group (61 interns receiving the thinking pattern of "Six Thinking Hats" combined with CBL-RISE teaching). After teaching, the two groups were compared in terms of assessment scores, self-learning ability, clinical thinking ability, self-expression ability, and recognition of teaching. SPSS 22.0 was used to perform the t-test and the chi-square test. Results:The observation group had significantly higher theoretical and skill assessment scores than the control group [mastery of basic knowledge: (55.42±3.65) vs. (49.57±3.23), P<0.05; case analysis: (20.13±2.19) vs. (16.42±2.74), P<0.05; medical record writing: (18.29±2.17) vs. (15.12±2.05), P<0.05; operational ability: (20.32±2.04) vs. (17.51±1.89), P<0.05; performance score: (30.34±3.24) vs. (27.19±3.07), P<0.05]. After practice teaching, both groups had increases in the scores of self-learning ability and clinical thinking ability, and the observation group had significantly higher scores than the control group [self-learning ability: (90.73±6.88) vs. (85.54±6.53), P<0.05; clinical thinking ability: (105.62±10.19) vs. (100.47±10.45), P<0.05]. Compared with the control group, the observation group had a significantly better self-expression ability ( P<0.05) and a significantly higher degree of recognition of teaching ( P<0.05). Conclusions:The thinking pattern of "Six Thinking Hats" combined with CBL-RISE teaching can improve the assessment scores of interns in thoracic surgery and stimulate their learning ability, thinking ability, and self-expression ability.

Objective This article reported the treatment process and pharmaceutical monitoring points of a 73 year old patient with latent tuberculosis and positive hepatitis B core antibody,whose focal segmental glomerulosclerosis(FSGS)was trea-ted with cyclosporine and rituximab instead of glucocorticoids because of gastrointestinal ulcer.Methods Clinical pharmacist participated in the treatment process of immunosuppressive therapy,infection prevention,and complications management of ne-phrotic syndrome,and then conducted pharmaceutical monitoring.Results The patient's nephrotic syndrome was relieved,and the urine protein decreased from around 8 g to below 1 g,indicating good disease control.Conclusion The combination of rituximab and cyclosporine could achieve in partial or nearly complete relief of nephrotic syndrome.For patients with latent tuber-culosis and hepatitis B core antibody positive,attention should be paid to the prevention of infection when using immunosuppres-sants such as monoclonal antibody.As patients with nephrotic syndrome were treated with multiple medications,drug interactions and concentrations monitoring should be focused on when using cyclosporine,as well as regular follow-up of patients and guarding against adverse reactions including renal dysfunction and infection.The participation of clinical pharmacists in the clinical therapy was of great significance,which ensured the effectiveness of disease treatment and medication safety.

Objective To investigate the changes in microglia phenotype after cerebral ischemia reperfusion(1R)injury and the effects of adenosine on nerve injury of cerebral IR injured rats.Methods Thirty-six healthy male Sprague Dawley rats were randomly divided into the sham operation(Sham)group,IR group,and adenosine pretreatment(AP)group,with 12 rats in each group.Before modeling,rats in the AP group were intraperitoneally injected with 2 mL of adenosine injection daily for 3 consecutive days,and rats in the Sham group and IR group were intraperitoneally injected with 2 mL of normal saline daily for 3 consecutive days.The middle cerebral artery occlusion models of rats in the IR group and AP group were constructed by using the suture-occluded method,and only the carotid artery of rats was isolated in the Sham group without ligation of blood vessels.At 2 hours after modeling,the neuroethology of rats in each group were evaluated according to a 5-point neurobehavioral scale.At 24 hours after restoring the blood perfusion in the middle cerebral artery,the rats in each group were executed,and their brain tissues were removed.The morphological changes of the brain tissues in the ischemic penumbra region were observed after hematoxylin-eosin(HE)staining.The co-expression of M1-type microglia markers and M2-type microglia markers was detected by immunofluorescence staining.The relative expression levels of pro-inflammatory factors inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α)and interleukin(IL)-1β released by M1-type microglia,and anti-inflammatory factors IL-4,IL-10 and transforming growth factor-β(TGF-β)released by M2-type microglia were detected by quantitative real-time polymerase chain reaction(qRT-PCR).Results The neurobehavioral scores of rats in the IR group and AP group were significantly higher than those in the Sham group,and the neurobehavioral score of rats in the IR group was significantly higher than that in the AP group(P＜0.05).HE staining results showed that the brain cells of rats in the Sham group were structurally complete and tightly arranged,with visible nuclei and no interstitial edema;the brain cells of rats in the IR group were structurally damaged and irregularly arranged,with loose cytoplasm and vacuoles in the cytosome;the structure of brain cells of rat in the AP group was better than that in the IR group,and there were many regularly-arranged normal cells,with complete nuclei.Immunofluorescence staining results showed that the number of M1-type and M2-type microglia in the ischemic penumbra region of rats in the IR group and AP group was significantly higher than that in the Sham group;the number of M1-type microglia in the IR group was significantly higher than that in the AP group,and the number of M2-type microglia was significantly lower than that in the AP group(P＜0.05).qRT-PCR results showed that the relative expression levels of pro-inflammatory cytokines TNF-α,IL-1β,iNOS and anti-inflammatory cytokines IL-4,IL-10,TGF-β in the IR group and AP group were significantly higher than those in the Sham group(P＜0.05);the relative expression levels of pro-inflammatory factors TNF-α,IL-1β and iNOS in the AP group were significantly lower than those in the IR group(P＜0.05),while the relative expression levels of anti-inflammatory factors IL-4,IL-10 and TGF-β were significantly higher than those in the IR group(P＜0.05).Conclusion AP can promote the polarization of microglia from M1 type to M2 type,inhibit the release of pro-inflammatory factors,increases the expression of anti-inflammatory factors,and thus has a neuroprotective effect on rats after cerebral IR injury.

Objective:To establish the normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province.Methods:A prospective study was conducted on healthy Han-nationality children aged 3-12 who took physical examination in Wuhan Children′s Hospital, Hubei province from January to August 2021.The children were asked for their medical histories, and those with neurological diseases, psychiatric diseases, infection, trauma, and a drug history in the past 2 weeks were excluded.The plasma of 324 children (262 males, 62 females; 217 cases in the 3-7 years old, 107 cases in the 8-12 years old) and urine of 391 children (302 males, 89 females; 266 cases in the 3-7 years old, 125 cases in the 8-12 years old) were collected.They ultra performance liquid chromatography-mass spectrometry multiple techniques (UPLC-MS/MS) were used to detect 10 kinds of neurotransmitters (e.g., dopamine, epinephrine, glutamic acid, etc.) in plasma and 8 kinds of neurotransmitters (e.g., dopamine, epinephrine, 5-hydroxyindoleacetic acid, etc.) in random urine.The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province was established.The Kruskal- Wallis H test was made for statistical analysis of the differences in neurotransmitter levels among different age groups and gender groups.The neurotransmitter levels between different groups were compared by the Nemenyi test. Results:There were no significant differences in the levels of various neurotransmitters in children of different genders(all P>0.05). There were significant differences in the levels of dopamine, methoxy-norepinephrine, tryptophan and γ-aminobutyric acid in the plasma of children aged 3-7 years and 8-12 years.There were significant differences in the levels of dopamine, epinephrine, norepinephrine, methoxy-norepinephrine, high vanillic acid and 5-hydroxyindoleacetic acid in the random urine between the 3-7 years old group and the 8-12 years old group. Conclusions:The normal reference range of neurotransmitters in Han-nationality children aged 3-12 in Hubei province is established.This study provides reference for clinical practice and lays a foundation for the study of neurotransmitter-related diseases in children.

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

This study firstly introduced the mechanism, benefits and applications of irreversible electroporation(IRE) for tumor ablation. In addition, this study also introduced the most advanced IRE systems cleared by FDA or CFDA and IRE research equipment. The clinically licensed IRE systems include the Nanoknife 3.0 of Angiodynamics, the Dophi
Electricity ; Electroporation ; Heart Rate ; Humans ; Neoplasms/therapy*