Three carboline fluorescent probes F1-F3 were designed and synthesized, based on lead compound JYJ-19, an antifungal compound discovered previously by our group. The antifungal activity in vitro results showed that compound F1 had moderate antifungal activity (MIC₈₀ = 32 μg·mL^-1). The stokes shift of F1 is 70 nm. The fluorescent probe F1 has good optical properties and can be used for fluorescence imaging research. Subcellular localization experiments results showed that F1 was enriched in the mitochondria of fungal cells. The detection of intracellular reactive oxygen species levels shows that JYJ-19 enhances intracellular reactive oxygen species levels. The above results indicated that carboline compounds could exert antifungal effects by acting on fungal mitochondria.

Cadmium is one of the heavy metals with severe reproductive toxicity,whose half-life lasts 20 to 40 years.Cadmium could induce dysfunction of testis and epididymis for its significant accumulation in human testis,and the amount,motility parameters and morphology of sperm change abnormally.The adverse change could also extend to male offspring and cause the impairment of their reproductive system.There has been no clear mecha-nism of how cadmium induces dysfunction of male reproductive system,and treatment for the adverse influence on male reproductive system by cadmium has not yet been found.Therefore,this problem has been discussed in repro-ductive and environmental field for a long time.A number of previous investigations showed that cadmium could damage male fertility by followed pathways,including interfering with hormone secretion,inducing oxidative stress,activating inflammation and apoptosis,and causing energy metabolism disorder,etc.In order to enlighten new ideas for therapeutic targets of male reproductive function damage induced by cadmium,we systematically reviewed and summarized the findings of previous publications in this paper.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

ObjectiveTo explore the interaction between bruceoside B and gut microbiota and the inhibitory activity of its metabolites on human lung cancer A549 cells， and to explore the value of bruceoside B in the treatment of non-small cell lung cancer（NSCLC）. MethodBruceoside B was co-incubated with the human gut microbiota under anoxic conditions in vitro， and ultra high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS） was used to analyze the metabolic transformation products. Cell counting kit-8（CCK-8） assay was performed to determine the effects of bruceoside B and its metabolites on the proliferation of human lung cancer A549 cells and the half inhibitory concentration（IC₅₀） was calculated. Five healthy male rats were gavaged with bruceoside B（2 mg·kg^-1） for 7 days after adaptive feeding. The feces of rats were collected before and after administration. 16S rRNA sequencing was used to assess gut microbiota. ResultBruceoside B was mainly metabolized to brusatol by human gut microbiota， the IC₅₀ of bruceoside B and the conversion product to A549 cells were 1 755.50， 19.57 μmol·L^-1， respectively， and the conversion product had a better activity at inhibiting A549 cells proliferation than bruceoside B. Additionally， The results of intestinal flora analysis showed no significant differences in α diversity and β diversity of gut microbiota after administration. In terms of species abundance， at the phylum level， bruceoside B decreased the relative abundance of Actinobacteriota and Proteobacteria， increased the relative abundance of Firmicutes， Patescibacteria and Cyanobacteria. At the genus level， bruceoside B decreased the relative abundance of Staphylococcus， Aerococcus and Psychrobacter， increased the relative abundance of Romboutsia， Lactobacillus， Clostridium sensu stricto 1， Norank-f-norank-o-Clostridia-UCG-014， Turicibacter， Allobaculum and Candidatus Saccharimonas. The results of functional prediction showed that the gut microbiota functional compositions were relatively stable. ConclusionBruceoside B can be deglycosylated by intestinal flora and converted into brusatol， with a significant increase in antitumor activity. The administration of bruceoside B will not cause significant changes in the structure and function of the intestinal flora， resulting in intestinal microecological balance disorders， and the administration appears to be beneficial to the intestinal flora of NSCLC patients.

Recently,inductively coupled plasma mass spectrometry(ICP-MS)has shown great potential in the quantitative analysis of biomolecules due to its high sensitivity,high accuracy,anti-interference ability and multi-element detection capability.Elemental tags enable specific labeling of target biomolecules with element-reporter groups,playing a critical role in the performance of bioanalysis using ICP-MS.Antibodies are highly specific to antigens on cell surfaces and are one of the most commonly used targeted delivery vehicles.Traditional random chemical coupling methods are difficult to control the coupling sites and loading numbers of element reporters,which lead to heterogeneity of antibody conjugates,affecting the specific recognition and binding ability of antibodies and antigens,and thus reducing the targeting ability and quantitative accuracy.To solve these issues,site-specific coupling of antibodies with element reporter was studied in this work.By using peptide-mediated affinity labeling technology,a short chain DNA was specifically labeled to immunoglobulin G(IgG)antibody K248,and then DNA base complementary pairing was used to realize accurate assembly of monoclonal antibodies and Eu-modified phage MS2 capsid,resulting in the preparation of highly sensitive and selective element tags.This method overcame the heterogeneity problem of element tags caused by random coupling,and ensured the targeting specificity,affinity and signal amplification ability of element tags.The element tag prepared here showed a specificity to bind/label with epidermal growth factor receptor(EGFR)biomarker on the surface of cancer cells,realizing single cancer cell analysis using ICP-MS.

Objective To observe the therapeutic effect and compatibility mechanism of Wumei Wan on diabetic gastroparesis(DGP)mice.Methods Sixty-nine C57BL/6J mice were randomly divided into normal group(12 mice)and model group(57 mice).The DGP model was constructed by 60％high-fat diet combined with intraperitoneal injection of streptozotocin(STZ).After successful modeling,the mice in the model group were randomly divided into model group,Wumei Wan whole prescription group,Wumei Wan sour medicine group,Wumei Wan bitter medicine group,Wumei Wan sweet medicine group and Wumei Wan pungent medicine group,with nine mice in each group.After 28 days of treatment,the gastric emptying rate and small intestinal propulsion rate of mice were measured.The pathological changes of gastric antrum were observed by hematoxylin-eosin(HE)staining.The fasting blood glucose(FBS)of mice was detected by blood glucose meter.The levels of triglyceride(TG),total cholesterol(TC)and low density lipoprotein cholesterol(LDL-C)were detected by colorimetry.The contents of gastrin(GAS),motilin(MTL)and vasoactive intestinal peptide(VIP)in gastric antrum were detected by enzyme-linked immunosorbent assay(ELISA).Western Blot was used to detect the expression of Kelch-like ECH-associated protein 1(Keap-1),nuclear factor erythroid 2-related factor 2(Nrf-2),NAD(P)H:quinone oxidoreductase 1(Nqo-1)and superoxide dismutase 1(Sod-1)in gastric antrum tissue.Results(1)Compared with the normal group,the levels of serum FBS,TG,TC and LDL-C in the model group were significantly increased(P＜0.05 or P＜0.01 or P＜0.001);compared with the model group,the blood glucose level of the whole prescription group,the sour medicine group and the bitter medicine group was decreased significantly at the end of the third and fourth week(P＜0.05 or P＜0.01 or P＜0.001),the serum TG,TC and LDL-C levels of the whole prescription group were significantly decreased(P＜0.05 or P＜0.01),the serum TC level of the sour medicine group,the bitter medicine group,the sweet medicine group and the pungent medicine group was significantly decreased(P＜0.05),and only the LDL-C level of the sour medicine group was significantly decreased(P＜0.05).(2)Compared with the normal group,the glandular cells in the gastric antrum mucosa and submucosa of the model group were disordered;compared with the model group,the pathological damage of gastric antrum tissue in Wumei Wan whole prescription group was significantly improved,the recovery effect of gastric antrum tissue damage in DGP mice in the sour medicine group and the bitter medicine group was superior to that in the sweet medicine group and the pungent medicine group.(3)Compared with the normal group,the gastric emptying rate and small intestinal propulsion rate of the model group were decreased(P＜0.01 or P＜0.001);compared with the model group,the gastric emptying rate of the whole prescription group,the sour medicine group and the bitter medicine group was significantly increased(P＜0.05 or P＜0.001),and the intestinal propulsion rate of the whole prescription group,the sour medicine group,the bitter medicine group,the sweet medicine group and the pungent medicine group was significantly increased(P＜0.05 or P＜0.01 or P＜0.001).(4)Compared with the normal group,the content of VIP in the gastric antrum tissue of the model group was significantly increased(P＜0.01),and the contents of GAS and MTL were significantly decreased(P＜0.01 or P＜0.001).Compared with the model group,the content of GAS in Wumei Wan whole prescription group,the sour medicine group,the bitter medicine group and the sweet medicine group was significantly increased(P＜0.01 or P＜0.001),the content of MTL in the whole prescription group and the bitter medicine group was significantly increased(P＜0.05 or P＜0.01),and the content of VIP in gastric antrum tissue of mice in Wumei Wan whole prescription group,sour medicine group,bitter medicine group and sweet medicine group was significantly decreased(P＜0.05 or P＜0.01 or P＜0.001).(5)Compared with the normal group,the expression level of Keap-1 in the gastric antrum tissue of the model group was increased(P＜0.05),and the expressions of Nrf-2,Nqo-1 and Sod-1 were decreased(P＜0.05 or P＜0.001).Compared with the model group,the expression level of Keap-1 protein in the whole prescription group and the bitter medicine group was significantly decreased(P＜0.05 or P＜0.001),and the expression levels of Nrf-2,Nqo-1 and Sod-1 in the whole prescription group,the sour medicine group and the bitter medicine group were significantly increased(P＜0.05 or P＜0.001).Conclusion Wumei Wan can effectively regulate glucose and lipid metabolism,improve gastric antrum injury and promote gastrointestinal motility in DGP mice.The efficacy of the whole prescription is superior to that of each disassembled prescription.The mechanism may be related to the synergistic compatibility of sour medicine,bitter medicine,sweet medicine and pungent medicine,and mainly through sour medicine and bitter medicine regulating Nrf-2/Keap-1 pathway further to improve oxidative stress injury.

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 summarize the reasons and management strategies of reoperation after oblique lateral interbody fusion(OLIF),and put forward preventive measures.Methods From October 2015 to December 2019,23 patients who under-went reoperation after OLIF in four spine surgery centers were retrospectively analyzed.There were 9 males and 14 females with an average age of(61.89±8.80)years old ranging from 44 to 81 years old.The index diagnosis was degenerative lumbar intervertebral dics diseases in 3 cases,discogenie low back pain in 1 case,degenerative lumbar spondylolisthesis in 6 cases,lumbar spinal stenosis in 9 cases and degenerative lumbar spinal kyphoscoliosis in 4 cases.Sixteen patients were primarily treated with Stand-alone OLIF procedures and 7 cases were primarily treated with OLIF combined with posterior pedicle screw fixation.There were 17 cases of single fusion segment,2 of 2 fusion segments,4 of 3 fusion segments.All the cases underwent reoperation within 3 months after the initial surgery.The strategies of reoperation included supplementary posterior pedicle screw instrumentation in 16 cases;posterior laminectomy,cage adjustment and neurolysis in 2 cases,arthroplasty and neuroly-sis under endoscope in 1 case,posterior laminectomy and neurolysis in 1 case,pedicle screw adjustment in 1 case,exploration and decompression under percutaneous endoscopic in 1 case,interbody fusion cage and pedicle screw revision in 1 case.Visu-al analogue scale(VAS)and Oswestry disability index(ODI)index were used to evaluate and compare the recovery of low back pain and lumbar function before reoperation and at the last follow-up.During the follow-up process,the phenomenon of fusion cage settlement or re-displacement,as well as the condition of intervertebral fusion,were observed.The changes in in-tervertebral space height before the first operation,after the first operation,before the second operation,3 to 5 days after the second operation,6 months after the second operation,and at the latest follow-up were measured and compared.Results There was no skin necrosis and infection.All patients were followed up from 12 to 48 months with an average of(28.1±7.3)months.Nerve root injury symptoms were relieved within 3 to 6 months.No cage transverse shifting and no dislodgement,loosening or breakage of the instrumentation was observed in any patient during the follow-up period.Though the intervertebral disc height was obviously increased at the first postoperative,there was a rapid loss in the early stage,and still partially lost after reopera-tion.The VAS for back pain recovered from(6.20±1.69)points preoperatively to(1.60±0.71)points postoperatively(P＜0.05).The ODI recovered from(40.60±7.01)％preoperatively to(9.14±2.66)％postoperatively(P＜0.05).Conclusion There is a risk of reoperation due to failure after OLIF surgery.The reasons for reoperation include preoperative bone loss or osteoporosis the initial surgery was performed by Stand-alone,intraoperative endplate injury,significant subsidence of the fusion cage after surgery,postoperative fusion cage displacement,nerve damage,etc.As long as it is discovered in a timely manner and handled properly,further surgery after OLIF surgery can achieve better clinical results,but prevention still needs to be strengthened.

Objective To investigate the effect of varying ureteral wall thickness(UWT)at the site of ureteral stones on the clinical efficacy of ureteroscopic lithotripsy(URL).Methods The clinical data of 164 patients with ureteral stones in our hospital were retrospectively analyzed.According to different UWT,the patients were divided into the mild thickening group(84 cases,UWT<3.16 mm),the moderate thickening group(31 cases,UWT 3.16 to 3.49 mm),and the severe thickening group(49 cases,UWT>3.49 mm),and the differences of clinical related indicators among the three groups were compared.Results The incidence of postoperative renal colic and leukocyte disorder in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,and the differences were statistically significant(P<0.05).The postoperative catheterization time in the mild thickening group and the moderate thickening group were shorter than that in the severe thickening group,and the incidences of secondary lithotripsy,residual stones and stone return to kidney in the mild thickening group and the moderate thickening group were lower than those in the severe thickening group,with statistically significant differences(P<0.05).The length of hospital stay and hospitalization cost in the mild thickening group and the moderate thickening group were shorter/less than those in the severe thickening group,with statistically significant differences(P<0.05).Conclusion With the increase of UWT(especially when UWT>3.49 mm),the incidence of postoperative complications and hospitalization cost of URL increase to varying degrees,and the surgical efficacy decreases.In clinical work,UWT measurement holds potential value in predicting the surgical efficacy and complications of URL.

A quartz crystal microbalance(QCM)-systematic evolution of ligands by the exponential en-richment(SELEX)technique was developed to screen out aptamers with high affinity for arsenic(Ⅲ).A random single strand DNA library was designed and fixed on the mercaptoethylamine-modified crystal plate with arsenic(Ⅲ)as the target,and the free aptamer was captured in the solution,and the QCM-SELEX screening method was constructed.After 6 rounds of screening,the secondary library was se-quenced with high throughput method,and the 6S1 dissociation coefficient Kd value was 0.36 μmol/L based on QCM resonance frequency.Using 6S1 as a probe,the QCM biosensor was constructed for the detection of arsenic(Ⅲ).The sensor has a good linear relationship in the range of 0.01 μmol/L～0.2μmol/L,and the detection limit of arsenic(Ⅲ)is 5.2 nmol/L(3σ),indicatinggood selectivity.