OBJECTIVE: To analyze the effectiveness of single three-dimensional (3D)-printed microporous titanium prostheses and flap combined prostheses implantation in the treatment of large segmental infectious bone defects in limbs. METHODS: A retrospective analysis was conducted on the clinical data of 76 patients with large segmental infectious bone defects in limbs who were treated between January 2019 and February 2024 and met the selection criteria. Among them, 51 were male and 25 were female, with an age of (47.7±9.4) years. Of the 76 patients, 51 had no soft tissue defects (single prostheses group), while 25 had associated soft tissue defects (flap combined group). The single prostheses group included 28 cases of tibial bone defects, 11 cases of femoral defects, 5 cases of humeral defects, 4 cases of radial bone defects, and 3 cases of metacarpal, or carpal bone defects, with bone defect length ranging from 3.5 to 28.0 cm. The flap combined group included 3 cases of extensive dorsum of foot soft tissue defects combined with large segmental metatarsal bone defects, 19 cases of lower leg soft tissue defects combined with large segmental tibial bone defects, and 3 cases of hand and forearm soft tissue defects combined with metacarpal, carpal, or radial bone defects, with bone defect length ranging from 3.8 to 32.0 cm and soft tissue defect areas ranging from 8 cm×5 cm to 33 cm×10 cm. In the first stage, vancomycin-loaded bone cement was used to control infection, and flap repair was performed in the flap combined group. In the second stage, 3D-printed microporous titanium prostheses were implanted. Postoperative assessments were performed to evaluate infection control and bone integration, and pain release was evaluated using the visual analogue scale (VAS) score. RESULTS: All patients were followed up postoperatively, with an average follow-up time of (35.2±13.4) months. In the 61 lower limb injury patients, the time of standing, walk with crutches, and fully bear weight were (2.2±0.6), (3.9±1.1), and (5.4±1.1) months, respectively. The VAS score at 1 year postoperatively was significantly lower than preoperative one ( t=-10.678, P<0.001). At 1 year postoperatively, 69 patients (90.8%) showed no complication such as infection, fracture, prosthesis displacement, or breakage, and X-ray films indicated good integration at the prosthesis-bone interface. According to the Paley scoring system for the healing of infectious bone defects, the results were excellent in 37 cases, good in 29 cases, fair in 3 cases, and poor in 7 cases. In the single prostheses group, during the follow-up, there was 1 case each of femoral prostheses fracture, femoral infection, and tibial infection, with a treatment success rate of 94.1% (48/51). In lower limb injury patients, the time of fully bear weight was (5.0±1.0) months. In the flap combined group, during the follow-up, 1 case of tibial fixation prostheses screw fracture occurred, along with 2 cases of recurrent foot infection in diabetic patients and 1 case of tibial infection. The treatment success rate was 84.0% (21/25). The time of fully bear weight in lower limb injury patients was (5.8±1.2) months. The overall infection eradication rate for all patients was 93.4% (71/76). CONCLUSION The use of 3D-printed microporous titanium prostheses, either alone or in combination with flaps, for the treatment of large segmental infectious bone defects in the limbs results in good effectiveness with a low incidence of complications. It is a feasible strategy for the reconstruction of infectious bone defects.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Titanium ; Retrospective Studies ; Surgical Flaps ; Adult ; Prosthesis Implantation/methods* ; Plastic Surgery Procedures/methods* ; Treatment Outcome ; Prostheses and Implants ; Bone Diseases, Infectious/surgery* ; Extremities/surgery* ; Prosthesis Design

The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that regulates gene expression in a range of cells, including immune and epithelial cells. AhR signaling plays important roles in the immune system in both health and disease states. Tapinarof is a first-in-class small-molecule topical therapeutic AhR modulating agent launched for the treatment of psoriasis. To improve the activity and chemical stability of Tapinarof, a series of 2-phenylchromen-4-one derivatives were designed, synthesized and evaluated as novel AhR agonists. Compounds 5a, 5c, 5e and 5f potently activated AhR with an EC₅₀ value of 7, 9, 6 and 6 nmol·L^-1, respectively, which are 10-14 fold more potent than Tapinarof. Compounds 5a and 5e exhibit comparable inhibitory effects on IFN-γ production as Tapinarof. Furthermore, compounds 5a-5f exhibited favorable photochemical stability compared to Tapinarof. The compounds may eventually serve as lead compounds for the development of new AhR agonists.

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 monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the efficacy and adverse reactions of whole-lung low-dose radiotherapy (LDRT) in patients with severe/critical coronavirus disease 2019 (COVID-19).Methods:Eight patients with severe/critical COVID-19 treated in the Jiangyin Hospital Affiliated to Nantong University from January to June 2023 who were treated with whole-lung LDRT after deteriorating or failing to improve post-medical treatment were enrolled in this single-arm phase I clinical trial. They received anterior-posterior penetrating radiation in a supine or prone position, with a total dose range from 0.5 to 1.5 Gy and a dose weight ratio of 1∶1. The oxygenation status, inflammatory markers, and imaging changes before and after radiotherapy were analyzed, and patients were followed up for acute radiation-induced adverse reactions.Results:One week after LDRT, the SaO 2/FiO 2 or PaO 2/FiO 2 indices increased in seven patients (87.5%), inflammatory markers such as C-reactive protein (CRP) and interleukin-6 (IL-6) decreased in seven patients (87.5%), and chest CT/chest radiographs revealed a significant reduction in the extent of pneumonia involvement in 5 patients (62.5%). No evident acute radiation-related adverse reactions were observed. Conclusions:Whole-lung LDRT with a dose range from 0.5 to 1.5 Gy can reduce inflammatory markers, improve clinical symptoms, and promote inflammatory absorption in patients with severe/critical COVID-19 who responded poorly to medical treatment while not inducing acute adverse reactions.

Objective:To observe the clinical effect of electrophysiological technique in treating chronic prostatitis.Meth-ods:Choose 40 patients of chronic prostatitis/chronic pelvic pain syndrome(chronicprostatis/chronicpelvicpainsyndrome,CP/CPPS)in People's Hospital in Zhijin and People's hospital in Guizhou Province from January 2022 to April 2023,The patients were randomly divided into control group(n=20)and treatment group(n=20).The treatment group received low-frequency neuromuscular electri-cal stimulation combined with drug therapy,while the control group received drug therapy alone.The improvement of prostatitis symp-tom score(NIH-CPSI)and International Prostatitis Symptom score(IPSS)before and after treatment was compared and analyzed.Results:A total of 37 patients were followed up(1 patient in the treatment group withdrew due to hypersensitivity to the electrode;2 patients in the control group were lost to follow-up.)There was no significant difference in baseline data between the two groups(P>0.05).The NIH-CPSI score and IPSS score before and after treatment were compared between the two groups,and the difference was statistically significant(P<0.05).The IPSS score of the two groups after treatment was compared,the average reduction of the treat-ment group was15.84±0.92 points,and that of the control group was7.17±0.40 points,and the difference was statistically signifi-cant(t=4.792,P<0.05).The NIH-CPSI score of the two groups after treatment was compared,and the average reduction was 17.47±0.92 points in the treatment group and 10.56±0.49 points in the control group.The difference between the two groups was statistically significant(t=6.654,P<0.05).Conclusion:The effect of electrophysiological combined drug therapy is obviously better than that of simple drug therapy.Electrophysiological therapy for chronic prostatitis has definite clinical effect and is worth pro-moting and applying.

Objective To explore the effect and mechanism of microRNA-133a-3p(miR-133a-3p)on invasion and apoptosis of breast cancer cells through targeted regulation of cullin-associated NEDD8-dissociated 1(CAND1).Methods MCF-7 cells were divided into overexpression group(mimics miR-133 a-3p transfection),NC group(mimics control transfection),co-transfection group(mimics miR-133a-3p transfection with pcDNA-CAND1 co-transfection)and control group(only adding the same amount of transfection reagents).Flow cytometry was used to detect cell apoptosis,Transwell assay was used to detect cell invasion,and real-time fluorescence quantitative polymerase chain reaction was used to detect miR-133a-3p and CAND1 expression.Results After transfection,the expression levels of miR-133a-3p in control group,NC group,overexpression group and co-transfection group were 0.50±0.08,0.51±0.09,1.06±0.10 and 1.05±0.15,respectively;the expression of CAND1 mRNA were 0.91±0.09,0.91±0.07,0.80±0.10 and 1.21±0.10,respectively.There were statistically significant differences in the above indexes between the co-transfection group and the control group,the NC group(all P＜0.05),and there were statistically significant differences between the overexpression group and the control group,the NC group(all P＜0.05).The apoptosis rates in control group,NC group,overexpression group and co-transfection group were(7.88±1.62)％,(8.87±2.01)％,(53.41±5.46)％,(29.54±3.78)％,respectively.The number of invasive cells in control group,NC group,overexpression group and co-transfection group were 161.02±10.31,155.87±12.30,85.21±9.11 and 118.37±10.84,respectively.There were statistically significant differences in the above indexes between transfection group and overexpression group,control group and NC group(all P＜0.05),and there were statistically significant differences between overexpression group and control group and NC group(all P＜0.05).Conclusion Overexpression of miR-133a-3p in human breast cancer cells MCF-7 can inhibit CAND1 and promote apoptosis and invasion of MCF-7 cells.

Objective To observe the clinical efficacy and adverse drug reactions of recombinant human growth hormone on dwarfism in children with primary nephrotic syndrome.Methods Children with dwarfism in primary nephrotic syndrome were divided into control group and treatment group.Patients in control group were orally administered prednisone acetate tablets,with an initial dose of 2 mg·kg-1·d-1,at once,no more than 60 mg in a single day,and after a duration of 6 weeks of full dosage,the dosage was reduced by 2.5 mg every 2 weeks until the maintenance dose of 5-10 mg·d-1 was administered for 12 months.Patients in treatment group were injected subcutaneously with recombinant human growth hormone 0.15 U·kg-1 at 0.5 h before bedtime every night on the basis of control group for a period of 12 months.The levels of height,bone age,standard deviation fraction of height(HtSDS),insulin-like serum growth factor 1(IGF-1),insulin-like growth factor binding protein 3(IGFBP-3),and the incidence of adverse drug reactions were compared between the two groups.Results There were 63 cases in control group and 63 cases in treatment group.The height of the children in treatment group and control group after treatment were(146.48±6.76)and(138.62±4.95)cm;the HtSDS values were-1.72±0.18 and-1.97±0.20;the IGF-1 values were(158.86±18.24)and(113.14±15.88)ng·mL-1;IGFBP-3 values were(5.21±0.83)and(3.13±0.71)μg·mL-1,the differences were all statistically significant(all P＜0.05).The incidence of adverse drug reaction in treatment group and control group were 9.52％(6 cases/63 cases)and 3.17％(2 cases/63 cases),with no statistically significant difference(P＞0.05).Conclusion Recombinant human growth hormone has a definite clinical efficacy,high safety,and effective promotion of growth and development in the treatment of primary nephrotic syndrome in children with dwarfism.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.