The effect of porcine SIRT5 on replication of foot and mouth disease virus type O(FMDV-O)and the underlying regulatory mechanism were investigated.Western blot and RT-qPCR analyses were employed to monitor expression of endoge-nous SIRT5 in PK-15 cells infected with FMDV-O.Three pairs of SIRT5-specific siRNAs were synthesized.Changes to SIRT5 and FMDV-O protein and transcript levels,in addition to virus copy numbers,were measured by western blot and RT-qPCR analyses.PK-15 cells were transfected with a eukaryotic SIRT5 expression plasmid.Western blot and RT-qPCR analyses were used to explore the impact of SIRT5 overexpression on FMDV-O replication.Meanwhile,RT-qPCR analysis was used to detect the effect of SIRT5 overexpression on the mRNA expression levels of type I interferon-stimulated genes induced by SeV and FMDV-O.The results showed that expression of SIRT5 was up-regulated in PK-15 cells infected with FMDV-O and siRNA interfered with SIRT5 to inhibit FMDV-O replication.SIRT5 overexpression promoted FMDV-O replication.SIRT5 over-expression decreased mRNA expression levels of interferon-stimulated genes induced by SeV and FMDV-O.These results suggest that FMDV-O infection stimulated expression of SIRT5 in PK-15 cells,while SIRT5 promoted FMDV-O rep-lication by inhibiting production of type I interferon-stimula-ted genes.These findings provide a reference to further ex-plore the mechanism underlying the ability of porcine SIRT5 to promote FMDV-O replication.

Objective To investigate the inhibitory effect of Sauchinone(Sch)on renal tissue fibrosis and to explore its mechanism in unilateral ureteral obstruction(UUO)mice.Methods Forty male ICR mice were divided into Sham,UUO-Model,Sch Low-dose,Sch High-dose,and positive control(Val)groups.Mice in the sham group underwent isolation of the left renal ureter without ligation,and mice in the UUO-Model group underwent stripping of the left proximal ureter for double ligation.Starting on day 2 after surgery,the Sch Low-dose group received 10 mg/kg Sch,the Sch High-dose group received 30 mg/kg Sch,and the Val group received 100 mg/kg valsartan by gavage once daily for 4 weeks.At the end of drug administration,serum creatinine(SCr),blood urea nitrogen(BUN),and the inflammatory factors tumor necrosis factor(TNF)-α and interleukin(IL)-6 were measured.Superoxide dismutase(SOD)activity,and malondialdehyde(MDA)and reactive oxygen species(ROS)content were detected in renal tissues.TNF-α and IL-6 mRNA levels were detected in renal tissues by reverse transcription-quantitative polymerase chain reaction.Pathological changes and collagen deposition,as well as transforming growth factor(TGF)-β1,Smad3,and connective tissue growth factor(CTGF)protein expression in mouse renal tissues were detected by hematoxylin and eosin and Masson staining,and immunohistochemistry.Collagen Ⅰ,CTGF,Smad3,nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and nuclear factor(NF)-κB protein expression in renal tissues were detected by Western Blot.Results SCr,BUN,TNF-α,and IL-6 were all significantly reduced in Sch Low-dose and Sch High-dose mice compared with the UUO-Model group(P＜0.05 or P＜0.01),while SOD activity was significantly higher and MDA and ROS levels were significantly lower in renal tissues(P＜0.05 or P＜0.01),and TNF-α and IL-6 mRNA in renal tissues were significantly reduced(P＜0.05 or P＜0.01).Microscopic observation of swollen renal tubules with thylakoid hyperplasia and collagen fiber deposition was significantly improved.Immunohistochemistry showed a significant reduction in TGF-β1,Smad3,and CTGF protein expression in renal tissues,and Western Blot showed significantly reduced levels of Collagen Ⅰ,CTGF,Smad3,and NF-κB protein expression(P＜0.05 or P＜0.01),while Nrf2 and HO-1 protein expression levels were significantly elevated(P＜0.05 or P＜0.01).Conclusions The amelioration of renal tissue fibrosis by sauchinone may be mediated via anti-inflammatory and antioxidative stress effects that modulate the expression of pro-fibrotic proteins in the TGF-β1/Smad3 signaling pathway.

Objective:To observe the genetic variation of SH2B3 in patients with myeloid neoplasms.Methods:The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology,Xuanwu Hospital,Capital Medical University from November 2017 to November 2022 were retrospectively analyzed,and the patients with SH2B3 gene mutations were identified.The demographic and clinical data of these patients were collected,and characteristics of SH2B3 gene mutation,co-mutated genes and their correlations with diseases were analyzed.Results:The sequencing results were obtained from 1 005 patients,in which 19 patients were detected with SH2B3 gene mutation,including 18 missense mutations(94.74％),1 nonsense mutation(5.26％),and 10 patients with co-mutated genes(52.63％).Variant allele frequency(VAF)ranged from 0.03 to 0.66.The highest frequency mutation was p.Ile568Thr(5/19,26.32％),with an average VAF of 0.49,involving 1 case of MDS/MPN-RS(with SF3B1 mutation),1 case of MDS-U(with SF3B1 mutation),1 case of aplastic anemia with PNH clone(with PIGA and KMT2A mutations),2 cases of MDS-MLD(1 case with SETBP1 mutation).The other mutations included p.Ala567Thr in 2 cases(10.53％),p.Arg566Trp,p.Glu533Lys,p.Met437Arg,p.Arg425Cys,p.Glu314Lys,p.Arg308*,p.Gln294Glu,p.Arg282Gln,p.Arg175Gln,p.Gly86Cys,p.His55Asn and p.Gln54Pro in 1 case each.Conclusion:A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms,among of them,p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.

Objective:To investigate the effect of feeder layer cells expressing interleukin(IL)-21 on the amplification of NK cells in vitro.Methods:The K562 cell line with IL-21 expression on its membrane was constructed by electroporation,and co-cultured with NK cells after inactivation.The proliferation of NK cells was observed.The killing function of the amplified NK cells in vitro was evaluated by the lactate dehydrogenase(LDH)and interferon-γ(IFN-y)release assay.A colorectal cancer xenograft model in NOD/SCID mice was established,and a blank control group,a NK cell group and an amplified NK cell group were set up to detect the tumor killing effect of amplified NK cells in vivo.Results:K562 cells expressing IL-21 on the membrane were successfully constructed by electroporation.After co-culturing with K562 cells expressing IL-21 on the membrane for 17 days,the NK cells increased to 700 times,which showed an enhanced amplification ability compared with control group(P＜0.001).In the tumor cell killing experiment in vitro,there was no significant difference in the killing activity on tumor cells between NK cells and amplified NK cells,and there was also no significant difference in mice in vivo.Conclusion:K562 cells expressing IL-21 on the membrane can significantly increase the amplification ability of NK cells in vitro,but do not affect the killing function of NK cells in vitro and in vivo.It can be used for the subsequent large-scale production of NK cells in vitro.

Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Purpose/Significance To explore the changes,challenges,key application scenarios and future development directions of generative artificial intelligence(AI)represented by ChatGPT in the field of hospital management,and to provide references for the ap-plication of AI natural language processing(NLP)technology in the field of hospital management in China.Method/Process Through literature review and analysis,the changes and challenges brought about by the rapid development of generative AI in the field of hospital management are sorted out,its key application scenarios and future development directions in the field of hospital management are empha-sized and explored.Result/Conclusion AI has broad application prospects in the field of hospital management,and it should focus on exploring its practical application scenarios and strategic directions to provide reference and guidance for promoting the high-quality de-velopment of public hospitals.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective:To observe the effect of point application-invigorate the spleen and kidney, circulation of blood formula (PA) combined with five-animal exercise (FAE) on improving the nutritional status for asthenia of patients with dialysis, and provide evidence for the rehabilitation treatment of dialysis patients.Methods:According to the random number table method, a total of 80 patients treated with regular dialysis at Department of Nephrology, the Affiliated Hospital of Nanjing University of Chinese Medicine from April 2020 to December 2021 were randomly divided into experimental group and control group, with 40 cases in each group. Participants in the control group received regular dialysis, basic treatment and diet nursing (RBD). Participants in the experimental group received RBD plus PA+FAE. Labaratory test results, Subjective Global Assessment scale score and Traditional Chinese medicine symptom score were measured at baseline and 12-weeks after the intervention. The Fried Frailty scale score was measured at baseline, 4, 8, and 12 weeks after the intervention.Results:The control group aged (54.08 ± 11.34) years old, 23 males, 17 females; the experimental group aged (57.38±9.89) years old, 19 males, 21 females. After 4, 8 and 12 weeks of intervention, the Fried Frailty Scale scores of the experimental group at different time points were 2 (2, 2), 1 (1, 2) and 1 (0, 1), respectively, lower than 3 (2, 4), 2 (2, 3) and 2 (2, 3) of the control group, and the differences in time effect, inter-group effect and interaction effect were statistically significant ( F=105.76, 18.38, 46.67, all P<0.01). Further pairwise comparisons within groups indicated significant differences of Fried Frailty scale scores at different time points ( Z=-2.78, -4.01, -6.08, all P<0.01). After 12-week of intervention, the results of hemoglobin, serum albumin and serum prealbumin were (107.88 ± 15.58) g/L, (39.10 ± 4.92) g/L, and (289.36 ± 72.05) mg/L in the experimental group, respectively, higher than (100.15 ± 17.62) g/L, (36.93 ± 4.72) g/L, (255.63 ± 75.35) mg/L in the control group ( t=-2.08, -2.01, -2.05, all P<0.05). Subjective Overall Assessment scale was found a significant difference between the 2 groups ( χ2=10.91, P<0.01): the number of grade A (good nutrition) and B (mild to moderate malnutrition) were 36 and 4 in the experimental group and 23 and 17 in the control group. Traditional Chinese medicine symptom score was (4.68 ± 2.50) in the experimental group, lower than (9.58 ± 4.40) in the control group ( t=6.13, P<0.01). Conclusions:Point application-invigorate the spleen and kidney and circulation of blood formula combined with five-animal exercise can effectively improve the nutritional status of dialysis patients and reduce the weakness of patients

Objective To evaluate the pharmacokinetics and safety of dapoxetine hydrochloride tablets in healthy Chinese subjects,and to assess the impact of food on dapoxetine pharmacokinetics.Methods A single-center,open-lable,two-period,randomized parallel study was conducted.A total of 22 healthy adult male subjects were enrolled and administered a single 30 mg oral dose of dapoxetine hydrochloride tablets,both under fasting and fed condition.Venous blood samples were collected at different time points,and dapoxetine concentrations in human plasma were measured using liquid chromatography tandem mass spectrometry(LC-MS/MS).Pharmacokinetic parameters were calculated using Phoenix WinNonlin 6.3 software,and statistical analysis was conducted with SPSS 19.0 software.Results The main pharmacokinetic parameters after oral administration of dapoxetine hydrochloride tablets in fasting and fed were as follows:Cmax were(230.71±88.91)and(216.27±58.32)ng·mL-1;AUC0-t were(1 054.99±442.11)and(1 292.56±534.49)ng·h·mL-1;AUC0-∞ were(1 175.03±510.58)and(1 447.42±656.25)ng·h·mL-1;tmax were(1.23±0.59)and(2.40±0.90)h;t1/2 were(15.95±6.13)and(16.21±6.34)h.Comparisons between the fasting and fed states,showed statistically significant differences in AUC0-t,AUC0-∞ and tmax(all P＜0.05),but not in Cmax and t1/2(all P＞0.05).The incidence of adverse events was 31.82％in the fasting state and 22.73％in the fed state,with no significant difference(P＞0.05).Conclusion Dapoxetine hydrochloride tablets were rapidly absorbed and eliminated in both fasting and fed states,with good safety;food slowed the absorption rate of dapoxetine and increaseed its overall exposure.

Objective To investigate the effect and mechanism of tetramethylpyrazine(TMP)on cognitive function in mice with post-traumatic stress disorder(PTSD).Methods The mice were randomly divided into normal group,model group and experimental group.Except for the normal group,the PTSD mouse model was established by single prolonged stress(SPS).The experimental group was intraperitoneally injected with 10 mg·kg-1 TMP,and the normal group and the model group were intraperitoneally injected with an equal amount of 0.9％NaCl.The Morris water maze,open field and elevated plus maze tests were used to evaluate the cognitive behavior of the mice.The apoptosis of neurons was detected by Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL).The expression of ionized calcium binding adapter molecule-1(Iba-1)protein was detected by immunofluorescence(ICC).The content of oxidative stress inflammatory factors was detected by enzyme-linked immunosorbent assay(ELISA).Results The escape latency of the normal group,model group,and TMP group were(56.50±9.89),(87.16±10.48)and(68.63±10.19)s,respectively;the corner residence time of the open field were(190.37±40.64),(260.39±40.54)and(218.63±38.27)s,respectively;the apoptosis rates were(18.28±2.35)％,(39.36±3.65)％and(30.74±3.58)％,respectively;the fluorescence intensities of Iba-1 were(8.01±2.23)％,(50.87±7.31)％and(7.49±1.41)％;malondialdehyde contents were(5.46±0.95),(12.98±2.06)and(8.31±1.28)nmol·mg-1,respectively;tumor necrosis factor-α contents were(53.59±9.91),(115.46±11.53)and(74.38±10.77)pg·mL-1,respectively.The above indexes in the normal group and the experimental group were statistically significant compared with the model group(P＜0.05,P＜0.01).Conclusion TMP can improve the cognitive function of PTSD mice,and the mechanism may be related to the regulation of inflammation and oxidative stress.