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.

Objective:To explore the influence of environment temperature on the incidence of testicular torsion.Methods:We collected the clinical data on 172 cases of testicular torsion diagnosed in the Second Hospital of Hebei Medical University from De-cember 2013 to December 2020.According to the local environment temperature on the day of onset,we divided the patients into groups A(below 0℃),B(0-10℃),C(10-20℃)and D(above 20℃),and compared the incidence rates of testicular torsion among the four groups,followed by correlation analysis.Results:The incidence rate of testicular torsion was 12.8％(n=22)in group A,35.5％(n=61)in B,34.9％(n=60)in C and 16.9％(n=29)in D,the highest at 0-10℃ in group B,with sta-tistically significant difference among the four groups(x2=29.07,P＜0.001).Spearman correlation analysis indicated that the inci-dence of testicular torsion was negatively correlated with the environment temperature(r=-0.261,P＜0.01),with no statistically significant difference among different seasons(x2=5.349,P＞0.05),but higher in autumn and winter than in the other two sea-sons.Conclusion:The incidence of testicular torsion is negatively correlated with the environment temperature,elevated when the temperature decreases,but has no statistically significant difference among different seasons,though relatively higher in autumn and winter.

Objective Using cochlear metabolomics to study the mechanisms underlying age-related hearing loss in rat.Methods A total of 30 rats with 2-month-old(young group)and 14-month-old(old group)were select-ed,with 15 rats in each group.The auditory function in each group was detected by auditory brainstem response(ABR),the morphology of cochlear tissue in both groups was observed using HE staining,and the oxidative stress status of cochlear tissue was detected by flow cytometry.Five rats/groups were selected for metabolomic examina-tion of cochlear tissue by untargeted ultra-high performance liquid chromatography-mass spectroscopy(LC-MS/MS)to analyze the metabolic differences in the aging cochlea.Results Compared with young group,ABR detection of tone burst at 8,16,and 32 kHz and click response thresholds were significantly higher in old group(P＜0.05),HE staining showed cochlear senescence-related vascular stripe atrophy(P＜0.05),and flow cytometric techniques suggested significantly higher levels of oxidative stress in old group(P＜0.05).Metabolomics detection revealed that a total of 124 differential metabolites were identified in the cochlea of the old group,of which 16 metabolites in-cluding sphingosine,all-trans-retinoic acid,and oleamide were significantly upregulated,while the levels of 108 me-tabolites such as purine,taurine,thiamine,and proline and its derivatives were significantly decreased.The results suggested that physiopathological mechanisms such as protein synthesis and catabolism,sphingolipid metabolism,purine metabolism,oxidative stress-related signaling,cell death,and coenzyme biosynthesis may be involved in co-chlear aging.Conclusion Cellular senescence and cochlear metabolic dysfunction may be important mechanisms of age-related hearing loss.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

AIM: To detect the expression of P53 and mTOR in pterygium tissues and healthy conjunctival tissues, and to explore the relationship between the expression of P53 and mTOR, and the relationship between the expression of P53 and mTOR and the important clinical features of pterygium.METHODS: The surgical specimens of 43 patients(43 eyes)who underwent pterygium excision and autologous conjunctival transplantation in the First Affiliated Hospital of Shihezi University from November 2022 to May 2023 were collected. Healthy conjunctiva group was selected from the healthy conjunctival tissue that originated from the temporal conjunctiva of 13 patients. Totally 10 pterygium specimens and 6 normal conjunctival specimens were selected and the qPCR was used to detect the mRNA expression levels of P53 and mTOR in pterygium and normal conjunctival tissues. Another 33 cases of pterygium and 7 cases of normal conjunctival tissues were collected and the expression of P53 and mTOR in pterygium and normal conjunctival tissues were detected by immunohistochemistry. IPP6.0 software was used to calculate the average optical density, the correlation between the expression levels of P53 and mTOR, and the correlation between the expression levels of P53 and mTOR and the important clinical features of pterygium were analyzed.RESULTS: According to qPCR results, the mRNA expression levels of TP53 and mTOR in the pterygium group were significantly higher than those in the healthy conjunctiva group(all P<0.05). According to the immunohistochemical staining results, the expression levels of P53 and mTOR proteins in the pterygium group were significantly higher than those in the healthy conjunctiva group(P<0.05). The expression of P53 was positively correlated with the expression of mTOR(r=0.417, P<0.05). The expression of P53 in the group of outdoor activity time > 3 h was higher than that in the group of outdoor activity time ≤3 h(P<0.05). The expression of P53 in the group of pterygium head invasive limbal distance > 2 mm was higher than that in the group of pterygium head invasive limbal distance ≤2 mm(P<0.05). There was no difference in the expression of pterygium between the two groups of patients aged > 40 years and ≤40 years(P>0.05). There was no significant difference in the expression of mTOR between the groups of outdoor activity time > 3 h and ≤3 h, the group of pterygium head invasion distance > 2 mm and ≤2 mm, and the group of > 40 years old and ≤40 years old(all P>0.05). The expression of P53 was positively correlated with the duration of outdoor activities(r=0.484, P<0.01)and the distance of limbal invasion(r=0.479, P<0.01). The expression of mTOR was not correlated with age, duration of outdoor activities, and distance of limbus invasion(all P>0.05).CONCLUSION: The overexpression of P53 and mTOR in pterygium showed a positive correlation, suggesting that the abnormal expression of P53 and mTOR may play a role in the pathogenesis of pterygium, which provides an experimental basis for further exploring the pathogenesis of pterygium; the expression of P53 is positively correlated with the time of outdoor activities and the distance of pterygium invasion. The P53 plays a role in evaluating the severity of pterygium, and provides new ideas for the clinical diagnosis and treatment of pterygium.

【Objective】 To explore the feasibility of en-bloc resection of bladder tumors by flexible cystoscope combined with laparoscopic instruments through urethra and to provide reference for the clinical application of this technique. 【Methods】 Self-designed and processed transurethral single-hole PORT and Olympus electronic cystoscope were used as observation mirror; Φ1.8 mm soft grasper, tissue scissors, electric hook, and ultrasonic scalpel were used as instruments; the porcine bladder was used as a model.The PORT was placed through the urethra, and the cystoscope was inserted to observe the inner wall of the bladder and the condition of the mucosa.After the lesion site was identified in the bladder cavity, the soft grasper was inserted to pull the mucosa to be removed, which was then fixed with tension at the target position to maintain a satisfactory feild of view.The surgeon held the cystoscope in the left hand, and operated the laparoscopic instruments into the bladder cavity through the PORT with the right hand.Observing with the cystoscope and lifting and pulling the mucosa with the grasper, the surgeon simulated the cutting and pushing actions to realize the en-bloc resection of the lesioned mucosa. 【Results】 The mucosa at 4 different locations were successfully resected on 2 in vitro porcine bladder models. 【Conclusion】 The in vitro experiments show that the combination of flexible electronic cystoscope and laparoscopic instruments achieves synergistic effects in en-bloc resection of bladder tumor by transurethral single-hole laparoscope without additional iatrogenic bladder injury caused by percutaneous bladder incision.This method is feasible in the treatment of bladder tumors, and has the potential of clinical application after further optimization.

Volume electron microscopy (vEM) imaging technology was rapidly developed in recent years. It has been the advanced technology to solve high-resolution three-dimensional structures of biological samples. Much wonderful work has revealed the fine structure and interactions of intracellular organelles, the ultrastructure of tissues, and even the three-dimensional structure of entire small biological organisms. With the continuous improvement of resolution, scale and throughput, vEM is becoming more and more widely used in medicine, life sciences, clinical diagnostics and other fields. As a result, this technology has been rated by Nature as one of the seven most noteworthy frontier technologies to watch in 2023. However, the development and application of vEM-related technologies started late in China and need to be further promoted. We write this review to introduce all related vEM technologies, covering the development history of vEM, technology classification, sample preparation, data collection, image processing, etc., which is convenient for people in various fields to understand, learn, apply and further develop this technology.

As a new transdermal drug delivery system, microneedles can significantly improve skin permeability, enhance drug transdermal delivery, and demonstrate unique advantages in breaking stratum corneum barrier of skin. This feature enables microneedles to demonstrate enormous potential in delivering biotechnology drugs. The traditional delivery method for biotechnology drugs is mainly injection, which brings problems such as pain and skin redness to patients, leading to poor patient compliance. In addition, the production, transportation, and storage of biotechnology drugs require strict low-temperature conditions to maintain their activity and increase cost output. Microneedles, by contrast, have many benefits, providing new avenues and solutions for biomolecular delivery. Accordingly, this review introduced the microneedle drug delivery system for delivery biotechnology drugs, and summarized the research progress of microneedle systems in biotechnology drugs.

Objective To evaluate the efficacy and safety of Chinese patent medicine combined with inhalation therapy for bronchial asthma in children with network meta-analysis.Methods CNKI,CBM,Wanfang Data,VIP,Embase,PubMed,and Web of Science were searched for obtaining the clinical randomized controlled trials of Chinese patent medicine combined with inhalation therapy for the treatment of bronchial asthma in children.Stata14 was used for network meta-analysis of the data.Results A total of 28 studies were eventually included,involving seven kinds of Chinese patent medicines,namely Hanchuan Zupa Granules,Huaiqihuang Granules,Tanreqing Injection,Xiaoer Feire Kechuan Granules,Chuankezhi Injection,Yupingfeng Granules and Zhubei Dingchuan Pills.The results of network meta-analysis showed that for improving the total effective rate,Tanreqing Injection combined with inhalation therapy,Chuankezhi Injection combined with inhalation therapy,and Zhubei Dingchuan Pills combined with inhalation therapy had the top 3 rankings of surface under the cumulative ranking curve(SUCRA).The optimal intervention measures to improve the peak expiratory flow(PEF),forced expiratory volume at one second(FEV1),and the ratio of FEV1 to forced vital capacity(FEV1/FVC)may separately be Tanreqing Injection combined with inhalation therapy,Hanchuan Zupa Granules combined with inhalation therapy,and Zhubei Dingchuan Pills combined with inhalation therapy.The analysis of the SUCRA ranking of the incidence of adverse reactions showed that Xiaoer Feire Kechuan Granules combined with inhalation therapy may be the intervention with the least side effects,and Zhubei Dingchuan Pills combined with inhalation therapy may be the intervention with greater side effects.Conclusion Compared with inhalation therapy alone,Chinese patent medicine combined with inhalation therapy can enhance the effective rate of bronchial asthma in children and improve lung function indicators,and has good safety.

The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.