A new treatment of concealed penis: symmetrical pterygoid flap surgery

ABSTRACT Purpose: Considerable controversy exists regarding the surgery for concealed penis. We describe a new technique for repairing concealed penis by symmetrical pterygoid flap surgery. Methods: From January 2016 to July 2022, we evaluated 181 cases of concealed penis that were surgically treated using the symmetrical pterygoid flap surgery. We measured the penile size preoperative and 2, 4, 12 weeks, and 1 year postoperative to confirm the improvement. A questionnaire was administered to the patients and parents to assess satisfaction regarding penile size, morphology, and hygiene. Result: The perpendicular penile length was1.59±0.32cm preoperative and 3.82±1.02 cm after the procedure (p < 0.05), and 4.21±1.91cm after one year of postoperative (p < 0.05). The overall satisfaction of patients was 97.89%, while the overall satisfaction of older children patients (age>7) was 75.24%. Parents focus more on the penile exposure size, while patients focus more on the penile morphology. Almost every patient had postoperative penile foreskin edema. However, this symptom had spontaneously resolved by 4-6 weeks. The complications such as skin necrosis, tissue contracture, or wound infection were 4.42%. Conclusion: The symmetrical pterygoid flap surgery is an effective surgical technique for the management of concealed penis in children producing predictable results and excellent satisfaction of the parents and patients.

Mechanism of Schisandra Chinensis-mediated microglia phenotypic transformation by regulation of the TLR4 pathway based on miR-124 / 药学学报

To investigate the mechanism by which Schisandra Chinensis mediates the phenotypic transformation of microglia via microRNA-124 (miR-124)-based regulation of the Toll-like receptor 4 (TLR4) pathway, a model was established using lipopolysaccharide (LPS) stimulation of BV2 cells. Cells were treated with different doses of Schisandra Chinensis extract (SCE). MiR-124 inhibitors and negative control sequences (NC inhibitor) were transfected into LPS-induced BV2 cells and treated with SCE. The MTT assay was used for cell activity detection; an NO kit was used to measure NO release; ELISA kits were used to measure the levels of interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α). Microglia markers, including ionized calcium binding adapter molecule-1 (IBA-1) and arginase-1 (Arg-1), and the nuclear translocation of nuclear factor-kappa B (NF-κB) were evaluated by immunofluorescent staining. NF-κB p65, IBA-1, Arg-1, TLR4, myeloid differentiation primary factor 88 (MyD88), inhibitor of nuclear factor-kappa B kinases-α (IKK-α), IL-10, TNF-α were detected by immunoblot. SCE at concentrations ranging from 31.25 to 250 μg·mL-1 had no significant effect on cell activity. SCE treatment significantly inhibited NO release induced by LPS (P < 0.001, P < 0.01), increased the level of IL-10 (P < 0.05), and decreased the level of TNF-α (P < 0.001). In addition, SCE significantly reduced the expression of TNF-α, IBA-1, TLR4, and MyD88 (P < 0.01, P < 0.001) and elevated the expression of IL-10, Arg-1, NF-κB P65 and IKK-α (P < 0.001, P < 0.01, P < 0.05). SCE treatment could also promote the expression of miR-124 (P < 0.01). However, transfection with the miR-124 inhibitor increased TNF-α (P < 0.001), decreased the level of IL-10 (P < 0.05), increased the mRNA level and the protein expression of TNF-α and IBA-1 (P < 0.05, P < 0.01, P < 0.001), and decreased the mRNA level and protein expression of IL-10 and Arg-1 (P < 0.001, P < 0.01). In addition, the inhibition of TLR4 and MyD88 was attenuated. In conclusion, SCE appears to inhibit the activation of TLR4 signaling pathway by upregulating miR-124 so as to inhibit microglia M1 polarization and promote microglia M2 polarization.

Autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations: a report of 8 cases and literature review / 中国当代儿科杂志

OBJECTIVES@#To summarize the clinical phenotype and genetic characteristics of children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations.@*METHODS@#A retrospective analysis was performed on the medical data of 8 children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations who were diagnosed and treated in the Department of Pediatrics, Xiangya Hospital of Central South University.@*RESULTS@#The mean age of onset was 9 months for the 8 children. All children had moderate-to-severe developmental delay (especially delayed language development), among whom 7 children also had seizures. Among these 8 children, 7 had novel heterozygous mutations (3 with frameshift mutations, 2 with nonsense mutations, and 2 with missense mutations) and 1 had 6p21.3 microdeletion. According to the literature review, there were 48 Chinese children with mental retardation caused by SYNGAP1 gene mutations (including the children in this study), among whom 40 had seizures, and the mean age of onset of seizures was 31.4 months. Frameshift mutations (15/48, 31%) and nonsense mutations (19/48, 40%) were relatively common in these children. In terms of treatment, among the 33 children with a history of epileptic medication, 28 (28/33, 85%) showed response to valproic acid antiepileptic treatment and 16 (16/33, 48%) achieved complete seizure control after valproic acid monotherapy or combined therapy.@*CONCLUSIONS@#Children with autosomal dominant mental retardation type 5 caused by SYNGAP1 gene mutations tend to have an early age of onset, and most of them are accompanied by seizures. These children mainly have frameshift and nonsense mutations. Valproic acid is effective for the treatment of seizures in most children.

Börjeson -Forssman -Lehmann syndrome: A case report / 中南大学学报(医学版)

Börjeson-Forssman-Lehmann syndrome (BFLS) is a rare X-linked intellectual disability. The main features of the patients include intellectual disability/global developmental delay, characteristic face, anomalies of fingers and toes, hypogonadism, linear skin hyperpigmentation, and tooth abnormalities in female patients, and obesity in male patients. A case of BFLS caused by a novel mutation of PHF6 gene who was treated in the Department of Pediatrics, Xiangya Hospital, Central South University was reported. The 11 months old girl presented the following symptons: Global developmental delay, characteristic face, sparse hair, ocular hypertelorism, flat nasal bridge, hairy anterior to the tragus, thin upper lip, dental anomalies, ankyloglossia, simian line, tapering fingers, camptodactylia, and linear skin hyperpigmentation. The gene results of the second-generation sequencing technology showed that there was a novel heterozygous mutation site c.346C>T (p.Arg116*) of the PHF6 (NM032458.3), variation rating as pathogenic variation. During the follow-up, the patient developed astigmatism, strabismus, awake bruxism, and stereotyped behavior, and the linear skin hyperpigmentation became gradually more evident. The disease is lack of effective therapy so far.

Factors influencing the efficacy of initial adrenocorticotropic hormone therapy for infantile epileptic spasms syndrome / 中国当代儿科杂志

OBJECTIVES@#To study the factors influencing the short-term (28 days) efficacy of initial adrenocorticotropic hormone (ACTH) therapy for infantile epileptic spasms syndrome (IESS), as well as the factors influencing recurrence and prognosis.@*METHODS@#The clinical data were collected from the children with IESS who received ACTH therapy for the first time in the Department of Pediatric Neurology, Xiangya Hospital of Central South University, from April 2008 to January 2018 and were followed up for ≥2 years. The multivariate logistic regression analysis was used to evaluate the factors influencing the short-term efficacy of ACTH therapy, recurrence, and long-term prognosis.@*RESULTS@#ACTH therapy achieved a control rate of seizures of 55.5% (111/200) on day 28 of treatment. Of the 111 children, 75 (67.6%) had no recurrence of seizures within 12 months of follow-up. The possibility of seizure control on day 28 of ACTH therapy in the children without focal seizures was 2.463 times that in those with focal seizures (P<0.05). The possibility of seizure control on day 28 of ACTH therapy in the children without hypsarrhythmia on electroencephalography on day 14 of ACTH therapy was 2.415 times that in those with hypsarrhythmia (P<0.05). The possibility of recurrence within 12 months after treatment was increased by 11.8% for every 1-month increase in the course of the disease (P<0.05). The possibility of moderate or severe developmental retardation or death in the children without seizure control after 28 days of ACTH therapy was 8.314 times that in those with seizure control (P<0.05). The possibility of moderate or severe developmental retardation or death in the children with structural etiology was 14.448 times that in those with unknown etiology (P<0.05).@*CONCLUSIONS@#Presence or absence of focal seizures and whether hypsarrhythmia disappears after 14 days of treatment can be used as predictors for the short-term efficacy of ACTH therapy, while the course of disease before treatment can be used as the predictor for recurrence after seizure control by ACTH therapy. The prognosis of IESS children is associated with etiology, and early control of seizures after ACTH therapy can improve long-term prognosis.

Analysis of the risk factors for poor prognosis and recurrence in patients with anti-NMDAR encephalitis / 中华预防医学杂志

To investigate the risk factors of poor prognosis and recurrence in patients with anti-NMDAR encephalitis. A single center, observational cohort study was used to retrospectively analyze 44 patients with anti NMDAR encephalitis hospitalized in the Department of Neurology of Beijing Tong Ren Hospital from January 2014 to October 2020. The results showed that the interval from onset to immunotherapy in the poor prognosis group was significantly longer than that in the good prognosis group (t=2.045,P=0.047), and the course of disease in the poor prognosis group was significantly longer than that in the good prognosis group (t=4.127,P=0.000 2). The number of patients with clinical manifestations of dyskinesia was significantly increased (Fisher exact test: P=0.014). The patients with abnormal brain MRI in the poor prognosis group were significantly more than those in the good prognosis group (Fisher exact test: P=0.017), and the patients with slow wave>50% in the poor prognosis group were significantly more than those with slow wave <50% (Fisher exact test: P<0.001). Patients with the first onset of immunotherapy time <3 months, long course of disease, high intracranial pressure, and high cerebrospinal fluid protein are prone to relapse. Bivariate logistic regression analysis showed that patients with dyskinesia, abnormal brain MRI, and slow wave EEG more than 50% were risk factors for poor prognosis (OR values were 4.687, 4.978, and 24.500, respectively; P values were 0.018, 0.016, and 0.000, respectively). The time of first-line immunotherapy for the first onset<3 months was the risk factor for recurrence (OR 17.231, P=0.010). In conclusion, dyskinesia, abnormal brain MRI and slow wave of EEG more than 50% may be the risk factors for poor prognosis of patients. The duration of immunotherapy less than 3 months after the first onset might be the risk factor for recurrence.

The expression and function of PD-L1 in CD133(+) human liver cancer stem-like cells / 中华肿瘤杂志

Objective: To investigate the expression of programmed death protein-ligand 1 (PD-L1) in liver cancer stem-like cells (LCSLC) and its effect on the characteristics of tumor stem cells and tumor biological function, to explore the upstream signaling pathway regulating PD-L1 expression in LCSLC and the downstream molecular mechanism of PD-L1 regulating stem cell characteristics, also tumor biological functions. Methods: HepG2 was cultured by sphere-formating method to obtain LCSLC. The expressions of CD133 and other stemness markers were detected by flow cytometry, western blot and real-time quantitative polymerase chain reaction (RT-qPCR) were used to detect the expressions of stemness markers and PD-L1. The biological functions of the LCSLC were tested by cell function assays, to confirm that the LCSLC has the characteristics of tumor stem cells. LCSLC was treated with cell signaling pathway inhibitors to identify relevant upstream signaling pathways mediating PD-L1 expression changes. The expression of PD-L1 in LCSLC was down regulated by small interfering RNA (siRNA), the expression of stem cell markers, tumor biological functions of LCSLC, and the changes of cell signaling pathways were detected. Results: Compared with HepG2 cells, the expression rate of CD133 in LCSLC was upregulated [(92.78±6.91)% and (1.40±1.77)%, P<0.001], the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were also higher than those in HepG2 cells (P<0.05), the number of sphere-formating cells increased on day 7 [(395.30±54.05) and (124.70±19.30), P=0.001], cell migration rate increased [(35.41±6.78)% and (10.89±4.34)%, P=0.006], the number of transmembrane cells increased [(75.77±10.85) and (20.00±7.94), P=0.002], the number of cloned cells increased [(120.00±29.51) and (62.67±16.77), P=0.043]. Cell cycle experiments showed that LCSLC had significantly more cells in the G(0)/G(1) phase than those in HepG2 [(54.89±3.27) and (32.36±1.50), P<0.001]. The tumor formation experiment of mice showed that the weight of transplanted tumor in LCSLC group was (1.32±0.17)g, the volume is (1 779.0±200.2) mm(3), were higher than those of HepG2 cell [(0.31±0.06)g and (645.6±154.9)mm(3), P<0.001]. The expression level of PD-L1 protein in LCSLC was 1.88±0.52 and mRNA expression level was 2.53±0.62, both of which were higher than those of HepG2 cells (P<0.05). The expression levels of phosphorylation signal transduction and transcription activation factor 3 (p-STAT3) and p-Akt in LCSLC were higher than those in HepG2 cells (P<0.05). After the expression of p-STAT3 and p-Akt was down-regulated by inhibitor treatment, the expression of PD-L1 was also down-regulated (P<0.05). In contrast, the expression level of phosphorylated extracellular signal-regulated protein kinase 1/2 (p-ERK1/2) in LCSLC was lower than that in HepG2 cells (P<0.01), there was no significant change in PD-L1 expression after down-regulated by inhibitor treatment (P>0.05). After the expression of PD-L1 was knockdown by siRNA, the expressions of CD133, Nanog, Oct4A and Snail in LCSLC were decreased compared with those of siRNA-negative control (NC) group (P<0.05). The number of sphere-formating cells decreased [(45.33±12.01) and (282.00±29.21), P<0.001], the cell migration rate was lower than that in siRNA-NC group [(20.86±2.74)% and (46.73±15.43)%, P=0.046], the number of transmembrane cells decreased [(39.67±1.53) and (102.70±11.59), P=0.001], the number of cloned cells decreased [(57.67±14.57) and (120.70±15.04), P=0.007], the number of cells in G(0)/G(1) phase decreased [(37.68±2.51) and (57.27±0.92), P<0.001], the number of cells in S phase was more than that in siRNA-NC group [(30.78±0.52) and (15.52±0.83), P<0.001]. Tumor formation in mice showed that the tumor weight of shRNA-PD-L1 group was (0.47±0.12)g, the volume is (761.3±221.4)mm(3), were lower than those of shRNA-NC group [(1.57±0.45)g and (1 829.0±218.3)mm(3), P<0.001]. Meanwhile, the expression levels of p-STAT3 and p-Akt in siRNA-PD-L1 group were decreased (P<0.05), while the expression levels of p-ERK1/2 and β-catenin did not change significantly (P>0.05). Conclusion: Elevated PD-L1 expression in CD133(+) LCSLC is crucial to maintain stemness and promotes the tumor biological function of LCSLC.

Research progress in control strategies of biological clock disorder / 生理学报

Circadian clock is an internal mechanism evolved to adapt to cyclic environmental changes, especially diurnal changes. Keeping the internal clock in synchronization with the external clock is essential for health. Mismatch of the clocks due to phase shift or disruption of molecular clocks may lead to circadian disorders, including abnormal sleep-wake cycles, as well as disrupted rhythms in hormone secretion, blood pressure, heart rate, body temperature, etc. Long-term circadian disorders are risk factors for various common critical diseases such as metabolic diseases, cardiovascular diseases, and tumor. To prevent or treat the circadian disorders, scientists have conducted extensive research on the function of circadian clocks and their roles in the development of diseases, and screened hundreds of thousands of compounds to find candidates to regulate circadian rhythms. In addition, melatonin, light therapy, exercise therapy, timing and composition of food also play a certain role in relieving associated symptoms. Here, we summarized the progress of both drug- and non-drug-based approaches to prevent and treat circadian clock disorders.

Research progress of artificial intelligence in 3D printed drugs / 药学学报

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

Multi-centre survey and analysis of individual therapy of antimicrobial agents in children / 中国药房

OBJECTIVE To investigate the development of individual therapy of antimicrobial agents in pediatric patients. METHODS A questionnaire survey was conducted to investigate the individual therapy of antimicrobial agents in 30 children’s hospitals and pediatric departments of general hospitals in China. The survey data was analyzed statistically by Microsoft Excel 2007 and SPSS 26.0 software. RESULTS In this survey， 75 questionnaires were collected， and 53 of them were valid with an effective rate of 70.7%. The results showed that 86.7% （26/30） of the hospitals carried out individual therapy of antimicrobial agents in different forms. Clinical needs primarily contributed to the individual therapy in these hospitals， while the insufficient personnel and equipment were the biggest obstacles for individual therapy. The proportions of hospitals， who implemented evidence- based pharmacy， therapeutic drug monitoring （TDM）， model-informed precision dosing （MIPD） and antimicrobial-related genetic tests were 70.0%， 80.0%， 30.0% and 33.3%， respectively. Various detection methods of TDM were carried out in various hospitals， and the antimicrobial agents which needed TDM focused on vancomycin and voriconazole. Moreover， nearly half of pharmacists did not know much about MIPD. CONCLUSIONS At present， TDM is the main way to develop individual therapy of antimicrobial agents in various hospitals， but its monitoring coverage and testing standards need to be improved. MIPD and antimicrobial-related gene tests still need to be further promoted in clinical practice.

Meta-analysis of efficacy and safety of CDK4/6 inhibitor combined with endocrine in the treatment of HR+/HER2－ breast cancer / 中国药房

OBJECTIVE To evaluate the efficacy and safety of four cyclin-dependent kinase 4/6 （CDK4/6） inhibitors （dalpicilib， abemacilib， ribocilib， palbocilib） combined with endocrine drugs in the treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative （HR+/HER2－） breast cancer. METHODS Computer searches were conducted on PubMed， the Cochrane Library， Web of Science， Embase， CNKI， Wanfang data and VIP to collect randomized controlled trials （RCTs） about CDK4/6 inhibitors combined with endocrine drugs （trial group） versus endocrine drugs alone or combined with placebo （control group）. The search period was from the establishment of the database to April 2023. After literature screening， data extraction and quality evaluation， a meta-analysis was conducted by using RevMan 5.4.1 software. RESULTS A total of 22 articles were included， involving 15 RCTs with a total of 18 574 patients. The meta-analysis results showed that the progression free survival [HR＝0.77， 95%CI （0.74， 0.79）， P＜0.000 1]， overall survival [HR＝0.91， 95%CI （0.87， 0.94）， P＜0.000 01]， objective response rate [OR＝1.71， 95%CI （1.51， 1.93）， P＜0.000 01] and clinical benefit rate [OR＝1.73， 95%CI （1.52， 1.95）， P＜0.000 01] of the trial group were significantly better than control group. The incidence of adverse drug reactions≥3 levels [OR＝10.28，95%CI （6.97，15.17），P＜0.000 01]， neutropenia [OR＝65.09， 95%CI （36.43， 116.31）， P＜0.000 01]， leukopenia [OR＝22.90， 95%CI （15.40， 34.04）， P＜0.000 01]， anemia [OR＝5.71， 95%CI （4.51， 7.22）， P＜0.000 01]， diarrhea [OR＝ 3.00， 95%CI （1.19， 7.51）， P＜0.05] and nausea [OR＝1.99， 95%CI （1.52， 2.60）， P＜0.000 01] in the trial group was significantly higher than control group. CONCLUSIONS The combination of CDK4/6 inhibitors and endocrine drugs has a significant effect on HR+/HER2－ breast cancer， with a high incidence of adverse reactions， especially hematotoxicity.

Congenital glycosylation disorder type Ⅱm caused by SLC35A2 mutations: a report of 3 cases and literature review / 中华神经科杂志

Objective:To summarize the clinical manifestations, gene variations, diagnosis and treatment of 3 cases with SLC35A2 variations characterized by congenital glycosylation disorder Ⅱm (CDG Ⅱm). Methods:A total of 3 patients admitted to the Department of Pediatrics of Xiangya Hospital of Central South University in China from 2018 to 2020 were examined in detail. The studies till January 2022 were searched with key words of "congenital disorders of glycosylation Ⅱm", " SLC35A2" and "CDG Ⅱm" in both English and Chinese in the databases of China National Knowledge Infrast Ructure (CNKI), Wanfang, Online Mendelian Inheritance in Man and PubMed, and the clinical manifestations, genetic variation, treatments and prognosis of patients with SLC35A2 mutation were summarized. Results:The patients all presented with intractable infantile spasm and global developmental delay, onset in infancy. A variety of antiepileptic treatments had temporary and partial efficacy. Otherwise, proband 2 and 3 presented with abnormal glutamic-pyruvic transaminase and increased platelets. Funduscopy showed dysplasia of the retinal pigment epithelium in both eyes, and they both received D-galactose treatment. A total of 22 relevant case reports, including 99 patients, were collected. The 99 patients all were heterozygous mutations, and a total of 75 different variation sites were reported. The clinical manifestations were characterized by global developmental delay or mental retardation ( n=89), epileptic seizure ( n=75), hypotonia ( n=57), facial deformity ( n=57), skeletal abnormality ( n=50), visual impairment ( n=42), elevated glutamic-pyruvic transaminase ( n=31), gastrointestinal symptoms ( n=28), skin deformity ( n=26), microcephaly ( n=23) and congenital heart disease ( n=12). Craniocerebral magnetic resonance imaging may be normal in the early stage. With age, magnetic resonance imaging may show abnormal white matter signals, brain atrophy, dysplasia of corpus callosum, delayed myelination, enlargement of lateral ventricle, brain stem atrophy and so on. Studies have shown that galactose treatment may be effective. Conclusions:SLC35A2 variants lead to CDG Ⅱm, whose clinical manifestations mainly include epileptic encephalopathy and global developmental delay. Multiple antiepileptic therapies can temporarily or partially control seizures, while oral galactose may improve the clinical symptoms, showing its prospect as a dietary therapy.

Global developmental delay and epileptic encephalopathy caused by SPTAN1 gene mutations in 3 cases and literature review / 中华神经科杂志

Objective:To summarize the clinical manifestations, gene variations,and treatment of cases with SPTAN1 gene variations characterized by global developmental delay or epileptic encephalopathy. Methods:Three patients with SPTAN1 gene mutations which caused developmental epileptic encephalopathy type 5 admitted to the Department of Pediatrics, Xiangya Hospital, Central South University from August 2019 to September 2021 were collected. The studies till December 2021 were searched with keywords of " SPTAN1" and "developmental and epileptic encephalopathy 5" in both English and Chinese databases of China National Knowledge Infrastructure, Wanfang, Online Mendelian Inheritance in Man, and PubMed. The clinical manifestations, genetic variations, treatments and prognosis of patients with SPTAN1 gene variations were summarized. Results:All 3 patients presented with global developmental delay, infant onset. Patient 1 showed early-onset epileptic encephalopathies and microcephaly. Patient 2 had an atrial septal defect. Cranial magnetic resonance imaging (MRI) of patient 3 showed cerebellar hypoplasia.Antiepileptic seizure therapy was partially effective, but failed to control the spasm. Development was slightly improved after rehabilitation training and other treatments, but still lagged behind the children of the same age. The SPTAN1 gene mutations of the 3 cases were heterozygous mutations, c.6923_6928dup, c.6619_6621delGAG and c.6749T>C, respectively. c.6749T>C was not reported in the previous literature. Thirteen case reports, including 69 patients, were collected. Sixty-seven patients had heterozygous mutations, inherited in an autosomal dominant fashion, including 35 missense mutations, 12 deletion mutations, 11 repetition mutations, 9 nonsense mutations, and the rest 2 patients had compound heterozygous missense mutations. A total of 38 different variation sites were reported. The phenotypes of 69 patients from the previous studies mainly included intellectual impairment (32/69), seizures (30/69), developmental delay (28/69), progressive microcephaly (27/69), hypotonia (23/69), poor visual attention (15/69), spastic quadriplegia (9/69), and gastrointestinal abnormalities (7/69). The primary type of seizures was epileptic spasm. Cranial MRI abnormalities mainly included cerebellar and brainstem atrophy, corpus callosum dysplasia, myelin dysplasia, and brain atrophy. Previous reports showed that a variety of anti-seizure drugs were effective for epileptic seizures. The prognosis varied greatly. Severe cases could be fatal, and mild cases only manifested as mild mental retardation or movement disorders. Conclusions:SPTAN1 gene mutation leads to developmental epileptic encephalopathy type 5, the phenotypes of which include intellectual impairment, global developmental delay, infantile spasms, and head deformity.Antiepileptic drugs and functional training can improve the symptoms, but the prognosis is still poor. This study expands the SPTAN1 gene variant spectrum, enriches the mutant spectrum of SPTAN1 gene associated with developmental epileptic encephalopathy type 5.

Development history of enhanced recovery after surgery and its applications during perioperative period of organ transplantation / 中华器官移植杂志

This systematical review focuse upon the development history of enhanced recovery after surgery(ERAS)and summarized its core strategies and developments in the field of organ transplantation, Clinicians should pay more attention to applying ERAS for perioperative management of transplantation and guiding clinical diagnoses and treatments.

HPLC Fingerprint Analysis of Benchmark Sample of Yanghetang / 中国实验方剂学杂志

ObjectiveTo establish a high performance liquid chromatography（HPLC） fingerprint of Yanghetang benchmark sample， and evaluate its quality with chemometric methods， so as to provide a reference for the quality control of this benchmark sample. MethodHPLC was used to establish the fingerprint of Yanghetang benchmark sample with ZORBAX SB-C18 column（4.6 mm×250 mm， 5 μm）， the mobile phase was consisted of acetonitrile（A） -0.05% phosphoric acid aqueous solution （containing 0.05% triethylamine solution）（B） for gradient elution（0-5 min， 2%-3%A； 5-15 min， 3%-5%A； 15-65 min， 5%-30%A； 65-90 min， 30%-70%A）， the flow rate was 1.0 mL·min-1， the column temperature was 35 ℃， and the detection wavelength was 210， 260 nm. Traditional Chinese Medicine（TCM） Chromatographic Fingerprint Similarity Evaluation System （2012 edition） combined with cluster analysis， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） were used to evaluate the quality differences between different batches of Yanghetang benchmark samples， and to find the main chemical components responsible for the quality differences. ResultHPLC fingerprint of Yanghetang benchmark sample was established， 13 common peaks were identified and attributed to each common peak， including peaks 2 and 8 from Rehmanniae Radix Praeparata， peaks 10 and 11 from Cinnamomi Cortex， peaks 1， 3-6 from fried Sinapis Semen， peak 13 from Ephedrae Herba， and peaks 7， 9， 12 from Glycyrrhizae Radix et Rhizoma. Eight of them were identified by comparing with control substance， which were 5-hydroxymethylfurfural（peak 2）， sinapine thiocyanate（peak 4）， glycyrrhizin（peak 7）， verbascoside（peak 8）， cinnamic acid（peak 10）， cinnamaldehyde（peak 11）， glycyrrhizic acid（peak 12） and ephedrine hydrochloride（peak 13）. The similarities of the HPLC fingerprints of 15 batches of Yanghetang benchmark samples with the control fingerprint were all greater than 0.80. The three chemometric methods could classify the samples into two categories. Eight differential components were screened out， among which 5-hydroxymethylfurfural， sinapine thiocyanate， verbascoside and ephedrine hydrochloride were identified. ConclusionThe established fingerprint analysis method is accurate， stable and reproducible， which basically reflects the overall chemical composition of Yanghetang benchmark sample， and can provide a basis for establishment of quality standards for compound preparations of this famous classical formula.

NEXMIF mutations in intellectual disability and epilepsy: A report of 2 cases and literature review / 中南大学学报(医学版)

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.

Synthesis, and anti-inflammatory activities of gentiopicroside derivatives / 中国天然药物

A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX-2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol·kg-1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.

Testosterone levels in patients with varicocele and azoospermia / 北京大学学报(医学版)

OBJECTIVE@#Androgen deficiency is common in aging males and may have unfavourable health consequences. Large-scale studies suggested low testosterone level might increse mortality and morbidity in ageing males. However, young men with low testosterone level might be neglected. Recent studies reported young men with infertility may have reduced testosterone level. To investigate the incidence of androgen deficiency in males with infertility and possible factors affecting the low testosterone level.@*METHODS@#Between January 2011 and December 2012, 407 men with infertility caused by varicocele (VC), obstructive azoospermia (OA) and nonobstructive azoospermia (NOA) in our center were included. The number of men in each group of OA, NOA and VC was 141, 97 and 169, respectively. All the eligible patients underwent a serum testosterone assessment by a single morning blood draw (between 8:00 to noon) to test for concentration of the total testosterone. All serum samples were determined by radioimmunoassay in our andrology laboratory. Androgen deficiency was defined as having a total testosterone level less than 300 ng/dL.@*RESULTS@#The mean age was (30.4±5.8) years. The mean testosterone level was (4.18±1.64) ng/dL (range 0.30 to 11.32 ng/dL). The overall incidence of androgen deficiency was 26.5% (108/407). The incidences of androgen deficiency in NOA, OA and VC groups were 40.2% (39/97), 19.1% (27/141) and 24.9% (42/169), respectively, which were significantly higher in the NOA than in the VC and OA groups (P < 0.001). The incidences had no difference between the VC and OA groups (P=0.229). Univariate analysis revealed the cause of infertility, FSH and the mean testis volume as possible affecting factors for androgen deficiency. However, on multivariate analysis the only cause of infertility was an independent predictor. The incidence of androgen deficiency was the highest in the NOA group [OR 0.492 (95% confidence interval 0.288-0.840)].@*CONCLUSION@#NOA and varicocele might be risk factors of androgen deficiency. Young men with NOA may have a higher possibility of low testosterone level. Testosterone level should be followed up after NOA and varicocele treatment. Androgen deficiency should be assessed in males with infertility in clinical practice.

Application evaluation of a rapid fluorescence quantitative PCR method for the detection of SARS-CoV-2 / 中华微生物学和免疫学杂志

Objective:To establish and evaluate a rapid nucleic acid detection method for SARS-CoV-2 based on COYOTE ? Flash20 real-time fluorescent quantitative PCR instrument. Methods:A rapid reaction system was constructed by using specific primer and probe sets targeting ORF1ab and N gene of SARS-CoV-2, and the sensitivity and specificity of the system were verified. At the same time, 108 clinical samples of COVID-19 were used to evaluate the application of this method.Results:The detection method did not require nucleic acid extraction, and the manual operation time was only one minute. After the sample was sent to the system, the test could be completed in 30 minutes. The detection limit of this method was 4×10 2 copies/ml. It had no cross-reactivity with other human coronaviruses (including HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV and MERS-CoV) and other respiratory viruses. The evaluation of clinical sample application showed that the total coincidence rate with the conventional RT-qPCR which required nucleic acid extraction was 98.15%. Conclusions:Through the application evaluation of the rapid fluorescent quantitative PCR method of SARS-CoV-2, it was found that the method was simple, fast, specific and sensitive, and it was suitable for real-time and rapid detection needs in varieties of situations.

Compound heterozygous mutations in POLR3A gene cause global developmental delay with epilepsy and striatal degeneration / 中华神经科杂志

Objective:To investigate the clinical, imaging and genetic features of patients with global developmental delay combined with epilepsy and striatal degeneration caused by POLR3A gene mutations.Methods:A total of three patients from two families with non-consanguineous marriages admitted to the Department of Pediatric Neurology of Xiangya Hospital of Central South University in 2020 were examined in detail. Peripheral blood DNA was extracted, and whole-exome sequencing was performed on the patients, combined with Sanger sequencing for verification. The mutation and protein function predictor softwares were applied to analyze the mutation sites.Results:All three patients presented with global developmental delay, seizures, dystonia. Head magnetic resonance imaging of all patients suggested basal ganglia atrophy and striatal degeneration. All had compound heterozygous mutations of c.1980 G>C; c.1771-6 C>G and c.2044C>T; c.1771-7 C>G in POLR3A gene as indicated by whole-exome sequencing. Sanger sequencing validation confirmed that the compound heterozygous mutations were originated from the parents of probands from the two families, respectively. Bioinformatic analysis suggested pathogenic features of the mutations.Conclusions:Compound heterozygous mutations in POLR3A gene , including a splice site mutation result in global developmental delay combined with epilepsy, striatal degeneration. Clinicians should promote the awareness of POLR3 related spectrum disorders, thus make early recognition and diagnosis.