OBJECTIVE To investigate the mechanism of Xihuang pill （XHP） against diffuse large B-cell lymphoma （DLBCL）. METHODS The active ingredients of XHP and potential therapeutic targets for DLBCL were identified using TCMSP， GeneCards and DisGeNET databases. Protein-protein interaction networks were constructed using the String database and Cytoscape software to screen core components and core targets. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were then performed. The clinical relevance of core targets was analyzed using the GEPIA and PanCanSurvPlot databases. Molecular docking and molecular dynamics （MD） simulation were conducted to verify the interactions between core components and core targets， and the binding free energy was calculated using the molecular mechanics Poisson-Boltzmann surface area （MM-PBSA） method. The effects of XHP on DLBCL and the related molecular mechanisms were validated using CCK-8 assay， flow cytometry and Western blot. RESULTS Network pharmacology analysis identified 108 active ingredients of XHP and 410 potential therapeutic targets for DLBCL. Six core components （e.g.， 17 beta-estradiol， quercetin） and ten core targets [e.g.， tumor protein 53 （TP53）， proto-oncogene tyrosine-protein kinase Src （SRC）] were obtained. Enrichment analysis indicated that the anti-DLBCL effects of XHP were primarily associated with the apoptotic signaling pathway， the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway and so on. Clinical correlation analysis revealed that TP53 and SRC expression were significantly up-regulated in DLBCL tissues and associated with poor patient prognosis （P＜0.05）. Molecular docking， MD simulations and MM-PBSA calculations confirmed that the SRC-quercetin complex had a mail：stronger and more stable binding affinity. In vitro experiments demonstrated that XHP concentration-dependently inhibited the proliferation of DLBCL cells； compared with control group， XHP medium- and high-dose groups could significantly induce the apoptosis of SU-DHL2 and SU-DHL4 cells， and significantly down- regulated the expressions of SRC protein， phosphorylated （p）-PI3K/PI3K and p-Akt/Akt in SU-DHL4 cells （P＜0.05）. CONCLUSIONS XHP may inhibit the proliferation and induce the apoptosis of DLBCL cells by regulating the SRC/PI3K/Akt signaling pathway.

BACKGROUND:The traditional surgical treatment for stromal corneal dystrophy is penetrating keratoplasty.In recent years,more and more doctors are considering using deep lamellar keratoplasty to treat stromal corneal dystrophy.Few studies comparing penetrating keratoplasty and deep lamellar keratoplasty for stromal corneal dystrophy have been reported in China. OBJECTIVE:To compare the clinical efficacy of deep lamellar keratoplasty and penetrating keratoplasty in the treatment of stromal corneal dystrophy. METHODS:Fifty-seven patients(57 eyes)diagnosed with stromal corneal dystrophy and admitted at the General Hospital of Northern Theater Command from January 2000 to January 2018 were selected,including 18 males and 39 females,aged(52.9±20.0)years.They were divided into two groups based on the surgical procedure:21 cases(21 eyes)in the deep lamellar keratoplasty group and 36 cases(36 eyes)in the penetrating keratoplasty group.A 12-month follow-up was conducted to observe the best-corrected visual acuity,corneal endothelial cell density,corneal grafttransparency,intraoperative and postoperative complications,and recurrence of the original disease. RESULTS AND CONCLUSION:Visual acuity at 1,3,6,and 12 months postoperatively was higher than preoperatively in both groups(P<0.05).The postoperative best-corrected visual acuity between the two groups showed no significant difference(P>0.05).With the prolongation of postoperative time,the corneal endothelial cell density gradually decreased in the two groups,and the annual loss rate of corneal endothelial cell density in the penetrating keratoplasty group was higher than that of the deep lamellar keratoplasty group at 6 and 12 months postoperatively(P<0.05),while there was no significant difference in corneal grafttransparency between the two groups at 12 months postoperatively(P>0.05).There were six cases of complications in the deep lamellar keratoplasty group and 14 cases of complications in the penetrating keratoplasty group.There was no recurrence in 57 cases within 12 months after surgery,and the difference in recurrence rates between the two groups at 5 years after surgery was not significant(P>0.05).The graftsurvival rates at 5 years after surgery in the penetrating keratoplasty group and the deep lamellar keratoplasty group were 83%and 86%,respectively,and there was no significant difference between the two groups(P>0.05).To conclude,deep lamellar keratoplasty could be considered as an alternative to penetrating keratoplasty in the treatment of stromal corneal dystrophy.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Objective:To explore the improvement effect of Tiaojing Zhuyun formula combined with Dai meridian moxibustion on endometrial fibrosis in rats with intrauterine adhesions(IUA)by regulating M2 type macrophage polarization.Methods:SD rats were selected to establish an IUA model using a dual injury method of mechanical curettage and lipopolysaccharide infection,which were randomly separated into model group,Tiaojing Zhuyun formula group,Dai meridian moxibustion group,Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group,with 10 rats in each group,another 10 rats were regarded as a sham operation(control)group,after grouping and treatment,the number of embryo implantation of rats in each group after cage closure was detected;HE staining was applied to detect pathological morphology of uterine tissue in rats in different groups,and their endometrial thickness and glandular number were compared;Masson staining was applied to detect endometrial fibrosis in rats of each group,and the collagen volume fraction(CVF)was compared;ELISA was applied to detect serum levels of profibrotic factor TGF-β1,pro-inflammatory factors IL-1β and IL-6,and levels of procollagen type Ⅰ carboxy-terminal peptide(PⅠNP)and procollagen Ⅲ N-terminal peptide(PⅢNP)of rats in each group;immunofluorescence staining was applied to detect expressions of M2 type macrophage markers CD163 and CD68 in endometrium of rats in each group.Results:Compared with control group,model group showed obvious pathological damage to uterine tissue,thickness of endometrium was thinner,the number of glands and embryo implantation were obviously reduced(P<0.05),endometrial CVF,levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6,and the number of CD163 and CD68 positive cells in endometrium were increased(P<0.05);compared with model group,pathological damage to uterine tissue of rats in Tiaojing Zhuyun formula group,Dai meridian moxibustion group,Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group was reduced,thickness of endometrium,the number of glands and embryo implantation,and the numbers of CD163 and CD68 positive cells in endometrium were increased(P<0.05),endometrial CVF and levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6 were reduced(P<0.05);compared with Tiaojing Zhuyun formula group and Dai meridian moxibustion group,pathological damage to uterine tissue of rats in Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group was alleviated,thickness of endometrium,the number of glands and embryo implantation,and the number of CD163 and CD68 positive cells in endometrium were increased(P<0.05),endometrial CVF and levels of serum PⅠNP,P Ⅲ NP,TGF-β1,IL-1β and IL-6 were reduced(P<0.05);there was no obvious change in all indicators between Tiaojing Zhuyun formula+Dai meridian moxibustion group and Bujiale group(P>0.05).Conclusion:Combination of Tiaojing Zhuyun formula and Dai meridian moxibustion can promote the polarization of M2 type macrophages,thereby inhibiting inflammation and endometrial fibrosis in IUA rats,and improving their symptoms of uterine adhesions.

Artificial intelligence (AI) technology is a scientific and technological field that focuses on the research and development of systems that simulate, extend, and expand human intelligence activities. This field encompasses various applications such as image recognition, language processing, expert systems, and robotics. The advancement of AI has greatly improved the quality and efficiency of medical work, particularly in areas like medical imaging, clinical decision support, precision medicine, and healthcare management. These advancements have contributed to the establishment of more effective healthcare systems.Within the realm of AI in healthcare, the application of AI technology in oral and maxillofacial surgery continues to evolve, with scenarios such as assisting in the interpretation and analysis of dental medical images, predicting and diagnosing early oral and maxillofacial tumors, aiding in minimally invasive surgery, designing ideal and personalized surgical plans, and simplifying medical management tasks. Oral and maxillofacial surgeons, as well as radiologists, should embrace and utilize these emerging technologies, actively adapting to environmental changes and updates, and driving forward the development of the field of oral and maxillofacial surgery.In summary, the integration of AI into oral and maxillofacial surgery presents significant opportunities for advancing patient care, surgical efficiency, and medical research in this specialized area of medicine. This technological partnership has the potential to reshape the landscape of oral and maxillofacial healthcare, benefiting both practitioners and patients.

Objective To analyze clinical characteristics and therapeutic strategies for patients with Trichosporon asahii(T.asahii)bloodstream infection(BSI),and provide reference for clinical diagnosis and treatment for such disease.Methods Diagnosis and treatment process of a patient with T.asahii BSI were reported.China National Knowledge Infrastructure(CNKI),Wanfang,PubMed,and Web of Science databases were retrieved using key-words:"Trichosporon asahii"and"bloodstream infection".Patients'age,gender,underlying diseases,immune status,treatment,and clinical outcome as well as antimicrobial susceptibility testing results of T.asahii were ana-lyzed retrospectively.Results The leukemia patient developed T.asahii BSI during chemotherapy,and showed clinical improvement after treatment with fluconazole+flucytosine.A total of 44 cases(43 from literature plus this index case)were analyzed.Among these cases,28 were males,the median age was 54.5 years old.The underlying diseases were predominantly hematological diseases.Catheter,urinary tract,and skin were identified as concurrent culture-positive sites.Azoles exhibited good antimicrobial activity in vitro,with voriconazole showing the strongest activity and associated with significantly higher survival rates.Under the guidance of antimicrobial susceptibility tes-ting results,patients with fluconazole treatment had a higher survival rate.At minimum inhibitory concentrations(MICs)of 4-8 μg/mL of fluconazole,fluconazole combined with other agents was predominantly required.Am-photericin B demonstrated good in vitro activity,but the overall survival rate of patients was low when amphotericin B was used as monotherapy without azoles.Catheters removal,surgical intervention,and neutrophil recovery were influencing factors for enhanced survival rates.Conclusion BSI caused by T.asahii primarily occurs in patients with hematological diseases,with neutropenia being a high-risk factor.Infection sites at catheter,urinary tract,and skin may be infection sources.Clearing the source of infection and promoting the recovery of neutrophils can help to improve survival rates of patients.For voriconazole-intolerant patients,fluconazole monotherapy or in combination with flucytosine/amphotericin B can be used alternatively based on antimicrobial susceptibility testing results.

Objective To summarize the changing prevalence of carbapenem resistance in Enterobacterales based on the data of CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021 for improving antimicrobial treatment in clinical practice.Methods Antimicrobial susceptibility testing was performed using a commercial automated susceptibility testing system according to the unified CHINET protocol.The results were interpreted according to the breakpoints of the Clinical & Laboratory Standards Institute(CLSI)M100 31st ed in 2021.Results Over the seven-year period(2015-2021),the overall prevalence of carbapenem-resistant Enterobacterales(CRE)was 9.43％(62 342/661 235).The prevalence of CRE strains in Klebsiella pneumoniae,Citrobacter freundii,and Enterobacter cloacae was 22.38％,9.73％,and 8.47％,respectively.The prevalence of CRE strains in Escherichia coli was 1.99％.A few CRE strains were also identified in Salmonella and Shigella.The CRE strains were mainly isolated from respiratory specimens(44.23±2.80)％,followed by blood(20.88±3.40)％and urine(18.40±3.45)％.Intensive care units(ICUs)were the major source of the CRE strains(27.43±5.20)％.CRE strains were resistant to all the β-lactam antibiotics tested and most non-β-lactam antimicrobial agents.The CRE strains were relatively susceptible to tigecycline and polymyxins with low resistance rates.Conclusions The prevalence of CRE strains was increasing from 2015 to 2021.CRE strains were highly resistant to most of the antibacterial drugs used in clinical practice.Clinicians should prescribe antimicrobial agents rationally.Hospitals should strengthen antibiotic stewardship in key clinical settings such as ICUs,and take effective infection control measures to curb CRE outbreak and epidemic in hospitals.

Objective To characterize the changing species distribution and antibiotic resistance profiles of respiratory isolates in hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Methods Commercial automated antimicrobial susceptibility testing systems and disk diffusion method were used to test the susceptibility of respiratory bacterial isolates to antimicrobial agents following the standardized technical protocol established by the CHINET program.Results A total of 589 746 respiratory isolates were collected from 2015 to 2021.Overall,82.6％of the isolates were Gram-negative bacteria and 17.4％were Gram-positive bacteria.The bacterial isolates from outpatients and inpatients accounted for(6.0±0.9)％and(94.0±0.1)％,respectively.The top microorganisms were Klebsiella spp.,Acinetobacter spp.,Pseudomonas aeruginosa,Staphylococcus aureus,Haemophilus spp.,Stenotrophomonas maltophilia,Escherichia coli,and Streptococcus pneumoniae.Each microorganism was isolated from significantly more males than from females(P＜0.05).The overall prevalence of methicillin-resistant S.aureus(MRSA)was 39.9％.The prevalence of penicillin-resistant S.pneumoniae was 1.4％.The prevalence of extended-spectrum β-lactamase(ESBL)-producing E.coli and K.pneumoniae was 67.8％and 41.3％,respectively.The overall prevalence of carbapenem-resistant E.coli,K.pneumoniae,Enterobacter cloacae,Pseudomonas aeruginosa,and Acinetobacter baumannii was 3.7％,20.8％,9.4％,29.8％,and 73.3％,respectively.The prevalence of β-lactamase was 96.1％in Moraxella catarrhalis and 60.0％in Haemophilus influenzae.The H.influenzae isolates from children(＜18 years)showed significantly higher resistance rates to β-lactam antibiotics than the isolates from adults(P＜0.05).Conclusions Gram-negative bacteria are still predominant in respiratory isolates associated with serious antibiotic resistance.Antimicrobial resistance surveillance should be strengthened in clinical practice to support accurate etiological diagnosis and appropriate antimicrobial therapy based on antimicrobial susceptibility testing results.

Objective To investigate the distribution and antimicrobial resistance profiles of common pathogens isolated from cerebrospinal fluid(CSF)in CHINET program from 2015 to 2021.Methods The bacterial strains isolated from CSF were identified in accordance with clinical microbiology practice standards.Antimicrobial susceptibility test was conducted using Kirby-Bauer method and automated systems per the unified CHINET protocol.Results A total of 14 014 bacterial strains were isolated from CSF samples from 2015 to 2021,including the strains isolated from inpatients(95.3％)and from outpatient and emergency care patients(4.7％).Overall,19.6％of the isolates were from children and 80.4％were from adults.Gram-positive and Gram-negative bacteria accounted for 68.0％and 32.0％,respectively.Coagulase negative Staphylococcus accounted for 73.0％of the total Gram-positive bacterial isolates.The prevalence of MRSA was 38.2％in children and 45.6％in adults.The prevalence of MRCNS was 67.6％in adults and 69.5％in children.A small number of vancomycin-resistant Enterococcus faecium(2.2％)and linezolid-resistant Enterococcus faecalis(3.1％)were isolated from adult patients.The resistance rates of Escherichia coli and Klebsiella pneumoniae to ceftriaxone were 52.2％and 76.4％in children,70.5％and 63.5％in adults.The prevalence of carbapenem-resistant E.coli and K.pneumoniae(CRKP)was 1.3％and 47.7％in children,6.4％and 47.9％in adults.The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)and Pseudomonas aeruginosa(CRPA)was 74.0％and 37.1％in children,81.7％and 39.9％in adults.Conclusions The data derived from antimicrobial resistance surveillance are crucial for clinicians to make evidence-based decisions regarding antibiotic therapy.Attention should be paid to the Gram-negative bacteria,especially CRKP and CRAB in central nervous system(CNS)infections.Ongoing antimicrobial resistance surveillance is helpful for optimizing antibiotic use in CNS infections.

Objective To investigate the antimicrobial resistance of clinical isolates from elderly patients(≥65 years)in major medical institutions across China.Methods Bacterial strains were isolated from elderly patients in 52 hospitals participating in the CHINET Antimicrobial Resistance Surveillance Program during the period from 2015 to 2021.Antimicrobial susceptibility test was carried out by disk diffusion method and automated systems according to the same CHINET protocol.The data were interpreted in accordance with the breakpoints recommended by the Clinical and Laboratory Standards Institute(CLSI)in 2021.Results A total of 514 715 nonduplicate clinical isolates were collected from elderly patients in 52 hospitals from January 1,2015 to December 31,2021.The number of isolates accounted for 34.3％of the total number of clinical isolates from all patients.Overall,21.8％of the 514 715 strains were gram-positive bacteria,and 78.2％were gram-negative bacteria.Majority(90.9％)of the strains were isolated from inpatients.About 42.9％of the strains were isolated from respiratory specimens,and 22.9％were isolated from urine.More than half(60.7％)of the strains were isolated from male patients,and 39.3％isolated from females.About 51.1％of the strains were isolated from patients aged 65-＜75 years.The prevalence of methicillin-resistant strains(MRSA)was 38.8％in 32 190 strains of Staphylococcus aureus.No vancomycin-or linezolid-resistant strains were found.The resistance rate of E.faecalis to most antibiotics was significantly lower than that of Enterococcus faecium,but a few vancomycin-resistant strains(0.2％,1.5％)and linezolid-resistant strains(3.4％,0.3％)were found in E.faecalis and E.faecium.The prevalence of penicillin-susceptible S.pneumoniae(PSSP),penicillin-intermediate S.pneumoniae(PISP),and penicillin-resistant S.pneumoniae(PRSP)was 94.3％,4.0％,and 1.7％in nonmeningitis S.pneumoniae isolates.The resistance rates of Klebsiella spp.(Klebsiella pneumoniae 93.2％)to imipenem and meropenem were 20.9％and 22.3％,respectively.Other Enterobacterales species were highly sensitive to carbapenem antibiotics.Only 1.7％-7.8％of other Enterobacterales strains were resistant to carbapenems.The resistance rates of Acinetobacter spp.(Acinetobacter baumannii 90.6％)to imipenem and meropenem were 68.4％and 70.6％respectively,while 28.5％and 24.3％of P.aeruginosa strains were resistant to imipenem and meropenem,respectively.Conclusions The number of clinical isolates from elderly patients is increasing year by year,especially in the 65-＜75 age group.Respiratory tract isolates were more prevalent in male elderly patients,and urinary tract isolates were more prevalent in female elderly patients.Klebsiella isolates were increasingly resistant to multiple antimicrobial agents,especially carbapenems.Antimicrobial resistance surveillance is helpful for accurate empirical antimicrobial therapy in elderly patients.