OBJECTIVE To investigate and analyze the current management of drug clinical trial institutions in Jiangxi Province and the situation of undertaking drug clinical trials after the implementation of the filing system. METHODS A survey was conducted on 38 new institutions （obtained qualifications during the implementation of the filing system） and old institutions （obtained qualifications during the implementation of the recognition system） that had completed drug clinical trial institution qualification filing for more than one year in Jiangxi Province. The survey focused on the basic information of the institutions， the number of registered principal investigator （PI）， institutional hardware and information construction， personnel allocation and training， and drug registration clinical trials undertaken by the institutions. RESULTS Of 38 institutions surveyed， there were 22 general hospitals and 16 specialized hospitals； there were 24 old institutions and 14 new institutions. Whether in general hospitals or specialized hospitals， the old institutions were better than the new institutions in the number of approved beds， the number of outpatients， the number of inpatients， the number of specialties， and the number of PI； both old and new institutions had separate offices； all new institutions were set up with GCP pharmacy. The adoption of clinical trial management system in new institutions is significantly less than in old institutions. In the general hospital， both the number of full-time managers and the number of quality controllers in old institutions were significantly more than in the new institutions， while the opposite was true at the level of specialized hospitals. In terms of centralized training on GCP， new institutions were all better than the old ones. Whether in general hospitals or specialized hospitals， the number of drug registration clinical trial projects undertaken by new institutions was significantly less than that of old ones. CONCLUSIONS The new institutions are worse than the old institutions in comprehensive strength and information construction of hospitals， and the number of clinical trials undertaken by new institutions is also less than old institutions.

OBJECTIVES: To compare the efficacy of toric implantable collamer lens (Toric-ICL) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for myopia correction in patients with moderate to high myopia complicated with astigmatism. METHODS: We retrospectively collected data from 64 patients (aged 18-42 years) with moderate to high myopia complicated with astigmatism (128 eyes) undergoing either Toric-ICL (28 patients/56 eyes) or FS-LASIK (36 patients/72 eyes) at our department between January, 2019 and December, 2020. The changes of uncorrected distance visual acuity (UCVA), spherical equivalent (SE), mean astigmatism correction index (CI), corneal endothelial cell density (ECD) and intraocular pressure (IOP) following the procedures were compared between the two groups. RESULTS: In FS-LASIK group, all the eyes (72/72) achieved an UCVA≥1.0, similar to the rate in Toric-ICL group (55/56 eyes; P=0.2374). The postoperative SE was also comparable between FS-LASIK and Toric-ICL groups [0.43±0.06 D (range: -1.0 to 1.50 D) vs 0.38±0.05 D (range: -0.75 to 1.00 D); P=0.56]. The mean astigmatism CI was significantly higher in FS-LASIK group than in Toric-ICL group (0.8561 vs 0.7176; P<0.0001), and 88.89% of the eyes in FS-LASIK group and 69.64% in Toric-ICL group had postoperative astigmatism ≤0.50 D. No significant changes were observed in postoperative corneal ECD in FS-LASIK group, whereas ECD decreased significantly after the procedure in Toric-ICL group (P=0.0057). The patients undergoing Toric-ICL exhibited no significant changes of postoperative IOP, but the patients receiving FS-LASIK had significantly reduced IOP after the procedure (P<0.001). CONCLUSIONS Although the patients included in Toric-ICL group had higher myopia and astigmatism, Toric-ICL still showed better predictability and efficacy for astigmatic correction in Toric-ICL group. Toric-ICL is an effective and safe equivalent of FS-LASIK for correcting moderate myopia but can be more advantageous for correcting high myopia with astigmatism.
Humans ; Astigmatism/complications* ; Myopia/complications* ; Keratomileusis, Laser In Situ/methods* ; Retrospective Studies ; Adult ; Visual Acuity ; Adolescent ; Young Adult ; Treatment Outcome ; Male ; Lens Implantation, Intraocular/methods* ; Female ; Phakic Intraocular Lenses ; Intraocular Pressure

In recent years, significant progress has been made in the study of the complex pathophysiology of sepsis. However, sepsis remains the main cause of high mortality among critically ill patients worldwide. Early diagnosis, timely treatment, and accurate prediction of the prognosis are crucial for the successful treatment of septic patients. Lactic acid not only serves as a diagnostic indicator for septic shock but also participates in the immune response process of sepsis. It regulates gene epigenetic regulation through lactylation, thereby affecting the expression of related genes, cellular metabolism, and the immune response of the body. Therefore, it may become a new target for the treatment of sepsis. Lactate-related indicators, such as lactic acid/albumin ratio (LAR) and lactic acid/hematocrit ratio (LHR), also have important value in the prognosis assessment of septic patients and are superior to the evaluation efficacy of a single indicator. This is of great significance for timely detection of the changes in the condition of septic patients and their risk stratification and precise treatment. This review focused on the relationship between lactylation, lactatization, lactate-related indicators and sepsis, as well as the latest research progress. By revealing their roles in the occurrence, development and prognosis of sepsis, it provided new ideas for clinical diagnosis and treatment, uncovered new mechanisms of disease onset, guided disease risk stratification, optimized existing treatment strategies, and also offered new references and directions for basic research on lactate-related indicators.
Humans ; Sepsis/metabolism* ; Lactic Acid/metabolism* ; Prognosis ; Biomarkers/blood*

Objective To explore EEG characteristics and the therapeutic effect in children with electrical status epilepticus during slow sleep(ESES).Methods The eligible ESES cases in our center from 2014 to 2020 were included.The age at diagnosis of ESES,the duration of ESES,spike wave index(SWI)during wakefulness and the distribution of spike wave during the period of ESES,age at seizure onset,the clinical syndromes and the outcomes after treatment were analyzed.The ESES cases were divided into 4 groups according to the distribution of spike wave:focal ESES,unilateral ESES,bilateral asymmetric ESES,multiple foci ESES.The SWI during the awake stage were divided into 3 groups based on the different rates:≤20%,21%～49%,≥50%.The therapeutic outcomes were classified into three groups:satisfactory response,seizure control and ineffective.Results 50 cases were included,with 32 males and 18 females.The average onset age of ESES was 6 years and 7 months,and the average duration of ESES was 28 months.A significant correlation between the distribution of ESES and the thera-peutic effects was found,bilateral asymmetric ESES had a good therapeutic effects,while multiple foci ESES showed a poor therapeutic effects.The duration of ESES was significantly correlated with therapeutic effects,and the efficacy was worse when the duration was longer than 1 year.A significant relationship between the SWI during wakefulness of ESES and the therapeutic effects was detected,the patient with SWI≤20%during wakefulness had a good therapeutic effect.There was a negative correlation between the onset age of ESES and the duration of ESES and SWI index during wakefulness.There was a positive correlation between the duration of ESES and SWI index during wakefulness.Conclusion Our results suggest that onset age,distribution,duration and SWI during wake-fulness of ESES were correlated with therapeutic outcomes,The patient with SWI≤20%during wakefulness had a good therapeutic effect and have unfavorable outcomes with ESES last more than 1 year.The earlier onset of ESES,the longer duration of ESES and higher SWI during wakefulness will be showed..

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective:To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma.Methods:This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results:Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P=0.009), hemi-hepatectomy and extended resection ( P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR=1.43 (0.61-3.35), P=0.413;T3 vs. T1: OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions:Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective:To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy (DEE). Methods:Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected. The children were grouped based on their age of onset, clinical manifestations, neurodevelopmental status, and results of genetic testing. The correlation between SCN1A genotypes and clinical phenotypes was analyzed. Results:Among the 46 patients, 2 children (4.35%) had developed the symptoms before 3 months of age, 42 (91.30%) were between 3 to 9 months, and 2 cases (4.35%) were after 10 months. Two cases (4.35%) presented with epilepsy of infancy with migrating focal seizures (EIMFS), while 44 (95.7%) had presented with Dravet syndrome (DS), including 28 cases (63.6%) with focal onset (DS-F), 13 cases (29.5%) with myoclonic type (DS-M), 1 case (2.27%) with generalized type (DS-G), and 2 cases (4.55%) with status epilepticus type (DS-SE). Both of the two EIMFS children had severe developmental delay, and among the DS patients, 7 cases had normal development, while the remaining had developmental delay. A total of 44 variants were identified through genetic sequencing, which included 16 missense variants and 28 truncating variants. All EIMFS children had carried the c. 677C>T (p.Thr226Met) missense variant. In the DS group, there was a significant difference in the age of onset between the missense variants group and the truncating variants group ( P < 0.05). Missense variants were more common in D1 (7/15, 46.7%) and pore regions (8/15, 53.3%), while truncating variants were more common in D1 (12/28, 42.9%). Children with variants outside the pore region were more likely to develop myoclonic seizures. Conclusion:The clinical phenotypes of DEE are diverse. There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene. Missense variants outside the pore region are associated with a higher incidence of myoclonic seizures.

Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

Objective:To explore the feasibility of extracting the key plane of the normal fetal palate on the 11-13 + 6 week from tomography ultrasonography imaging based on artificial intelligence. Methods:The fetal volume datas of 235 cases of 11-13 + 6 week normal fetal were collected from the Department of Ultrasound in the Luohu District People′s Hospital of Shenzhen and Huazhong University of Science and Technology Union Shenzhen Hospital from May 2020 to April 2021. The data acquisition was completed by sonographers A and B by using the GE Voluson E10 color Doppler ultrasound diagnostic instrument. All datas were marked offline by sonographer C. Tomographic imaging was performed on all included data by sonographer D, the tomographic images were saved and the time-consuming was recorded, and the datas of the sonographer group were obtained. The labeled data were randomly divided into the training set and test set for model transfer learning and testing.The 4-fold cross-validation was adopted to record the test set image output by the model and the time consumption to obtain the intelligent group data. A senior sonographer performed image analysis on the two groups of data images. The feasibility of the intelligent model was verified by comparing the score of the plane of retronasal triangle(RTP), the acquisition rate of RTP, the acquisition rate of the fault, and the time-consuming difference between the sonographer group and the intelligent group. Results:①There was no significant difference in the overall distribution of RTP scores between the sonographer group and intelligent group [5 (5, 6) points vs 5 (5, 6) points, Z=0.355, P=0.722]. The RTP acquisition rate of the sonographer group and intelligent group was not statistically significant (78.72% vs 76.60%, χ 2=0.55, P=0.458). The consistency and correlation of RTP obtained by the two groups were high (Kappa=0.645, φ=0.646, both P<0.001). ②The effective layers of the sonographer group were 9 (8, 9) and the intelligent group was 8 (7, 9). The fault acquisition rate of the doctor group was higher than that of the intelligent group (78.72% vs 68.51%, χ 2=12.52, P=0.001). The consistency and correlation of the two groups in obtaining faults were media (Kappa=0.503, φ=0.521, both P<0.001). ③The time-consuming of the intelligent group was significantly lower than that of the sonographer group [1.50 (1.23, 1.75)s vs 26.94 (22.28, 30.48)s, Z=11.440, P<0.001]. Conclusions:This research model can quickly and accurately realize the extraction and tomography of the key plane of the normal fetal palate on the 11-13 + 6 week.

Objective:To report cases of multiple mitochondrial dysfunction syndrome 2 (MMDS2) caused by BOLA3 gene mutation, hoping to help clinical diagnosis. Methods:The medical records of a child with MMDS2 admitted to the Department of Neurology, Guangzhou Women and Children′s Medical Center in November 2021 were analyzed, and the clinical, imaging characteristics and prognosis of MMDS2 were summarized by literature review.Results:This 1 year and 9 months old male had a disease that started in childhood, with motor function regression and hyperlactatemia. Head magnetic resonance imaging indicated white matter lesions, and gene examination indicated the homozygous variation of BOLA3 gene c.295C>T(p.Arg99Trp). The diagnosis of MMDS2 was clear for the child. After treatment, the clinical symptoms and imaging of the child recovered significantly. Through literature review, 13 children with MMDS2 reported in 7 English literatures were reviewed. These cases had similar manifestations with the case reported in this study. Among them, 1 case recovered and 8 cases died in infancy. Conclusions:MMDS2 patients often show nervous system dysfunction such as motor regression, elevated lactate and white matter lesions, which often cause multiple system disorders. Some children die early, but some of them can be recovered.