AIM:To investigate the value of optical coherence tomography angiography(OCTA)indicators in the diagnosis of diabetic retinopathy(DR), and to provide patients with diabetic nephropathy(DN)with more sensitive OCTA screening indicators to detect concurrent DR at an early stage.METHODS: A total of 200 patients who treated in the ophthalmology department of the Seventh Affiliated Hospital, Sun Yat-sen University from 2022 to 2023 were included, including 95 first-diagnosed DR patients and 105 patients without DR, and all patients underwent OCTA examination and a collection of demographics and renal function parameters. After a quality check, automated measurements of the foveal avascular zone area, vessel density(VD), and perfusion density(PD)of both 3 mm×3 mm and 6 mm×6 mm windows were obtained.RESULTS: Using random forest and multivariate Logistic regression methods, we developed a diagnostic model for DR based on 12 variables(age, FBG, SBP, DBP, HbA1c, ALT, ALP, urea/Scr, DM duration, HUA, DN, and CMT). Adding specific OCTA parameters enhanced the efficacy of the existing diagnostic model for DR(outer vessel density in 6 mm×6 mm window, AUC=0.837 vs 0.819, P=0.03). In the study of DN patients, the parameters in the 6 mm×6 mm window improved the diagnostic efficacy of DR(inner VD; outer VD; full VD; outer PD; full PD).CONCLUSION:The outer VD in the 6 mm×6 mm window can enhance the efficacy of the traditional DR diagnostic model. Meanwhile, compared with the 3 mm×3 mm window, the microvascular parameters in the 6 mm× 6 mm window focusing on DN patients can be more sensitive to diagnosing the occurrence of DR.

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

Collateral vessels in cutaneous regions are the channel of qi， blood and body fluids transmission among the skin and striae and interstices， and is also the path of pathogens invasion. It is believed that the key pathogenesis of polymorphic light eruption （PLE） was toxins damaging to the skin， in which the cutaneous collaterals fail to nourish， insecurity of the muscle surface as the basis of disease， the pathogens offending qi collaterals and heat constraint to toxins as the driving factors， gradually affecting fluid collaterals and dryness-dampness coexist as the middle link， and latent pathogens in blood level and waiting for the opportunity to onset as the final stage. It is proposed that the basic treatment is to resolve toxins and tranquilize collaterals， and the internal and external treatments are combined together. The internal treatment is to resolve toxins， strengthen collaterals， and assist in unblocking the collaterals， and the modified self-prescribed Wuteng Decoction （五藤饮） plus Yigong Powder （异功散） were selected as the basic formulas， which promotes the discharge of toxin pathogens and strengthens the power of the cutaneous collaterals to protect against pathogens. For external treatment， according to the performance of skin lesions， scraping， tapping with medicinal solution， ointment were selected to drive away pathogens and resolve toxins， and soothe the cutaneous collaterals. In the early stage， the skin temperature rose with itching， tingling and no rash， scraping with the self-prescribed Yinhuangcao Clearing Oil （银黄草清解油） could be used to activate blood and regulate qi， relieve heat and resolve toxins； if the lesions showed erythema， pimples， itching， tapping with the self-prescribed Qian'ai Xunxi Formula （千艾熏洗方） could be used to diffuse qi and fluid， unblock the collaterals and clean toxins； if the skin lesions thickened with scales， the self-prescribed Yufu Ointment （愈肤膏） for external application could be used to resolve toxins and activate collaterals， moisten skin and heal up sore.

The membranous tube of sanjiao （三焦） is not only the path of the transport of fluid and qi， but the way of the invasion of pathogenic factors， therefore， it cooperates with the skin mucous membrane physically and influence on each other pathologically. It is believed that the core pathogenesis of chronic urticaria is pathogens intruding sanjiao， membrane collaterals acute spasm， and fluid and qi disturbance， of which defense qi insufficiency and pathogens intruding sanjiao initiates the disease， while struggle between healthy and pathogenic qi and membrane collaterals acute spasm is the intermediate stage， and disturbed fluid， qi and blood movement is the terminal stage. Following the core treatment principle of dredging sanjiao， the internal treatment is to open striae and interstices and dispel pathogens out using self-made Guben Shufeng Decoction（固本疏风汤）modifications， and the external treatment is to dredge and regulate membrane collaterals， move qi and fluid， and treat sanjiao simultaneously， commonly using cutting therapy on Danzhong （RN 17） to move qi and fluid， seal umbilical therapy on Shenque （RN 8） to supplement and nourish ying-wei （营卫）， and natural moxibustion on Xuehai （SP 10） to move blood and unblock collaterals.

Objective:To explore the value of common nutritional indexes to assess the severity of elderly patients with chronic obstructive pulmonary disease(COPD).Methods:The data of 94 elderly COPD patients who were hospitalized in the Department of Internal Medicine of Huangshan Shoukang Hospital from January 2018 to August 2020 were retrospectively analyzed.According to the final outcome of the patients,the patients were divided into improvement group(n=83)and ICU group(n=11).The nutritional status and lung functions of patients were assessed.Data including forced expiratory volume in one second/prediction(FEV1/Pre)was collected.The correlation of levels of body mass index(BMI),albumin,prealbumin,retinol binding protein,lymphocyte count,and geriatric nutritional risk index with FEV1/Pre was analyzed.And the value of these indexes in predicting whether patients needed to be transferred to ICU or not was analyzed.Results:Among the 94 patients,60 were male and 34 were female.The age ranged from 50 to 92 years old,and the quartile was 78(72,83)years old.The correlation coefficients between FEV1/Pre and levels of BMI,albumin,prealbumin,retinol binding protein,lymphocyte count,and geriatric nutritional risk index were 0.535(P<0.001),0.726(P<0.001),0.351(P=0.001),0.498(P<0.001),0.572(P<0.001),and 0.940(P<0.001),respectively.The areas under the ROC curve predicted by levels of BMI,albumin,prealbumin,retinol binding protein,lymphocyte count,and geriatric nutritional risk index were 0.744(95%CI:0.544～0.944,P<0.001),0.834(95%CI:0.669～1.000,P<0.001),0.658(95%CI:0.468～0.823,P<0.001),0.602(95%CI:0.408～0.811,P<0.001),0.649(95%CI:0.428～0.856,P<0.001),and 0.875(95%CI:0.751～0.999,P<0.001),respectively.Conclusions:Levels of BMI,prealbumin,retinol binding protein,lymphocyte count,and geriatric nutritional risk index had certain correlation with the severity of COPD,which could be used to assess the severity of COPD.The elderly nutritional risk index showed the best prediction value.

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 investigate the effect of Ilizarov technique combined with rotational center dome-shaped osteoto-my in the treatment of juvenile distal femoral valgus deformity.Methods A retrospective study was conducted to analyze the clinical data of 11 patients with valgus deformity of the distal femur who had been admitted and followed up completely from January 2016 to October 2020.There were 7 males and 4 females.The 6 patients were on the right side and 5 patients were on the left side.The age ranged from 10 to 14 years old.The center of roration of angulation(CORA)was identified at the distal femur deformity,and dome-shaped osteotomy was performed with the CORA as the midpoint.The annular external fixator was installed according to the needle threading principle of Ilizarov external fixation,and the distal femur was cut off.The valgus deformity under visual inspection of the distal femur was corrected immediately,and the external fixator was fixed and main-tained.The residual deformity and shortening were corrected according to the force line and length of the lower limbs suggested by the weight-bearing full-length anteroposterior and lateral X-rays of both lower limbs.Results All 11 patients were followed up for 13 to 25 months.The time of wearing external fixator was 12 to 17 weeks.In the last follow-up,both lower limbs were measured by the weight-bearing full-length anteroposterior and lateral X-rays,and the length of both lower limbs of 11 patients were equal,and the deformities were corrected.The score of hospital for special surgery(HSS)was used to evaluate the knee function,all of which were excellent.Conclusion The Ilizarov technique was applied in the treatment of distal femoral valgus deformity in adolescents using a rotating central dome-shaped osteotomy.Visual femoral valgus deformity was corrected imme-diately during the operation.After the operation,residual deformities and shortening were dynamically adjusted and corrected according to the force line and shortening degree of lower extremities indicated by the weight-bearing anteroposterior and lateral radiographs of both lower limbs,with minimal damage and fast recovery.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Human brain banks use a standardized protocol to collect,process and store post-mortem human brains and related tissues,along with relevant clinical information,and to provide the tissue samples and data as a resource to foster neuroscience research according to a standardized operating protocols(SOP).Human brain bank serves as the foundation for neuroscience research and the diagnosis of neurological disorders,highlighting the crucial rule of ensuring the consistency of standardized quality for brain tissue samples.The first version of SOP in 2017 was published by the China Human Brain Bank Consortium.As members increases from different regions in China,a revised SOP was drafted by experts from the China Human Brain Bank Consortium to meet the growing demands for neuroscience research.The revised SOP places a strong emphasis on ethical standards,incorporates neuropathological evaluation of brain regions,and provides clarity on spinal cord sampling and pathological assessment.Notable enhancements in this updated version of the SOP include reinforced ethical guidelines,inclusion of matching controls in recruitment,and expansion of brain regions to be sampled for neuropathological evaluation.

To investigate the protective effect and the potential mechanism of leonurine(Leo) against erastin-induced ferroptosis in human renal tubular epithelial cells(HK-2 cells), an in vitro erastin-induced ferroptosis model was constructed to detect the cell viability as well as the expressions of ferroptosis-related indexes and signaling pathway-related proteins. HK-2 cells were cultured in vitro, and the effects of Leo on the viability of HK-2 cells at 10, 20, 40, 60, 80 and 100 μmol·L~(-1) were examined by CCK-8 assay to determine the safe dose range of Leo administration. A ferroptosis cell model was induced by erastin, a common ferroptosis inducer, and the appropriate concentrations were screened. CCK-8 assay was used to detect the effects of Leo(20, 40, 80 μmol·L~(-1)) and positive drug ferrostatin-1(Fer-1, 1, 2 μmol·L~(-1)) on the viability of ferroptosis model cells, and the changes of cell morphology were observed by phase contrast microscopy. Then, the optimal concentration of Leo was obtained by Western blot for nuclear factor erythroid 2-related factor 2(Nrf2) activation, and transmission electron microscope was further used to detect the characteristic microscopic morphological changes during ferroptosis. Flow cytometry was performed to detect reactive oxygen species(ROS), and the level of glutathione(GSH) was measured using a GSH assay kit. The expressions of glutathione peroxidase 4(GPX4), p62, and heme oxygenase 1(HO-1) in each group were quantified by Western blot. RESULTS:: showed that Leo had no side effects on the viability of normal HK-2 cells in the concentration range of 10-100 μmol·L~(-1). The viability of HK-2 cells decreased as the concentration of erastin increased, and 5 μmol·L~(-1) erastin significantly induced ferroptosis in the cells. Compared with the model group, Leo dose-dependently increased cell via-bility and improved cell morphology, and 80 μmol·L~(-1) Leo promoted the translocation of Nrf2 from the cytoplasm to the nucleus. Further studies revealed that Leo remarkably alleviated the characteristic microstructural damage of ferroptosis cells caused by erastin, inhibited the release of intracellular ROS, elevated GSH and GPX4, promoted the nuclear translocation of Nrf2, and significantly upregulated the expression of p62 and HO-1 proteins. In conclusion, Leo exerted a protective effect on erastin-induced ferroptosis in HK-2 cells, which might be associated with its anti-oxidative stress by activating p62/Nrf2/HO-1 signaling pathway.
Humans ; Ferroptosis ; Reactive Oxygen Species/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Sincalide/pharmacology* ; Signal Transduction ; Epithelial Cells/metabolism* ; Glutathione