Distribution of traditional Chinese medicine syndrome types and elements in liver cirrhosis patients with dysplastic nodules: An analysis of 138 cases / 临床肝胆病杂志

Objective To investigate the distribution of traditional Chinese medicine (TCM) syndrome types and elements in liver cirrhosis patients with dysplastic nodules (DN), and to provide a basis for exploring the connotation and pattern of TCM syndrome types of DN in liver cirrhosis. Methods A total of 138 patients who attended The First Affiliated Hospital of Henan University of Chinese Medicine from March 2013 to January 2021 and were diagnosed with liver cirrhosis and DN were enrolled. General data such as age of onset and sex were collected, as well as the data on etiology, TCM syndrome types, and Child-Pugh class for liver function, and the distribution characteristics of TCM syndrome types and elements were summarized. The chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results The liver and the spleen were the main syndrome elements of disease location in liver cirrhosis patients with DN, accounting for 97.83% and 94.93%, respectively, followed by the kidney (23.91%); Qi deficiency and Qi stagnation were the main syndrome elements reflecting the nature of disease, accounting for 73.91% and 58.70%, respectively, followed by dampness (34.78%). The main TCM syndrome types included stagnation of liver Qi and spleen deficiency, damp-heat internal excess syndrome, blood stasis and toxin accumulation syndrome, and water-dampness retention syndrome, among which stagnation of liver Qi and spleen deficiency was more common and accounted for 58.70% ( P 0.05). There was a significant difference in Child-Pugh class between the liver cirrhosis DN patients with different TCM syndrome types ( χ 2 =34.320, P < 0.05), and Child-Pugh class A was more common in the patients with stagnation of liver Qi and spleen deficiency (59.8%), while Child-Pugh class C was more common in the patients with damp-heat internal excess syndrome (39.1%). Conclusion This article summarizes the distribution characteristics of common TCM syndrome types and elements of DN in liver cirrhosis, which provides a reference for the syndrome differentiation-based TCM treatment of DN in liver cirrhosis.

Clinical Efficacy of Dingkundan in Treatment of Ovulatory Disorder Infertility Based on Real-world / 中国实验方剂学杂志

ObjectiveTo explore the clinical efficacy of Dingkundan in the treatment of ovulation disorder infertility based on the real world and provide reliable evidence-based medical support for clinical practice. MethodClinical diagnosis and treatment data of patients with ovulation disorder infertility in the real world were collected through the Medroad Cloud system. Patients were grouped according to their real-world treatments， and the total effective rate， ovulation rate per cycle， number of days of follicle development， gonadotropin （Gn） dosage， levels of mature follicle-related hormones， endometrial thickness and classification， pregnancy rate per cycle， clinical pregnancy rate， ectopic pregnancy rate， and early pregnancy loss rate were observed. ResultA total of 207 patients were included， and the most common traditional Chinese medicine （TCM） syndrome in the entire population was liver depression and kidney deficiency. The patients were divided into a Chinese medicine group （Dingkundan， 60 cases）， a western medicine group （ovulation induction， 51 cases）， and a combination group （Dingkundan + ovulation induction， 96 cases）. The combination group（98.96%，95/96） had the highest total effective rate， which was statistically significant when compared with the Chinese medicine group（88.33%，53/60） （χ2=8.328， P<0.05）. The mature follicle estradiol （E2） and luteinizing hormone （LH） levels were the highest in the combination group， and there were statistically significant differences when compared with the western medicine group （P<0.01）. The endometrial thickness was higher in the Chinese medicine group and the combination group than in the western medicine group （P<0.01）. The proportion of type A endometrium was highest in the combination group（85.90%，201/234）， and there was a statistically significant difference when compared with the western medicine group（73.81%，93/126） （χ2=7.993， P<0.01）. The clinical pregnancy rate was 60.42%（58/96） in the combination group， which was higher than 36.67%（22/60） in the Chinese medicine group （χ2=8.336， P<0.01） and 39.22%（20/51） in the western medicine group （χ2=6.011， P<0.05）. Compared with the western medicine group， the combination group showed a favorable trend in total effective rate， ovulation rate per cycle， number of days of follicle development， Gn dosage， pregnancy rate per cycle， ectopic pregnancy rate， and early pregnancy loss rate， but the differences were not statistically significant. ConclusionIn real-world clinical practice， the combination of Dingkundan with ovulation induction can increase endometrial thickness， improve the proportion of type A endometrium， enhance egg quality， and increase the clinical pregnancy rate in patients with ovulation disorder infertility. This approach deserves further clinical research and application.

USH2A mutation and specific driver mutation subtypes are associated with clinical efficacy of immune checkpoint inhibitors in lung cancer / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

This study aimed to identify subtypes of genomic variants associated with the efficacy of immune checkpoint inhibitors (ICIs) by conducting systematic literature search in electronic databases up to May 31, 2021. The main outcomes including overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and durable clinical benefit (DCB) were correlated with tumor genomic features. A total of 1546 lung cancer patients with available genomic variation data were included from 14 studies. The Kirsten rat sarcoma viral oncogene homolog G12C (KRASG12C) mutation combined with tumor protein P53 (TP53) mutation revealed the promising efficacy of ICI therapy in these patients. Furthermore, patients with epidermal growth factor receptor (EGFR) classical activating mutations (including EGFRL858R and EGFRΔ19) exhibited worse outcomes to ICIs in OS (adjusted hazard ratio (HR), 1.40; 95% confidence interval (CI), 1.01‍‒‍1.95; P=0.0411) and PFS (adjusted HR, 1.98; 95% CI, 1.49‍‒‍2.63; P<0.0001), while classical activating mutations with EGFRT790M showed no difference compared to classical activating mutations without EGFRT790M in OS (adjusted HR, 0.96; 95% CI, 0.48‍‒‍1.94; P=0.9157) or PFS (adjusted HR, 0.72; 95% CI, 0.39‍‒‍1.35; P=0.3050). Of note, for patients harboring the Usher syndrome type-2A(USH2A) missense mutation, correspondingly better outcomes were observed in OS (adjusted HR, 0.52; 95% CI, 0.32‍‒‍0.82; P=0.0077), PFS (adjusted HR, 0.51; 95% CI, 0.38‍‒‍0.69; P<0.0001), DCB (adjusted odds ratio (OR), 4.74; 95% CI, 2.75‍‒‍8.17; P<0.0001), and ORR (adjusted OR, 3.45; 95% CI, 1.88‍‒‍6.33; P<0.0001). Our findings indicated that, USH2A missense mutations and the KRASG12Cmutation combined with TP53 mutation were associated with better efficacy and survival outcomes, but EGFR classical mutations irrespective of combination with EGFRT790M showed the opposite role in the ICI therapy among lung cancer patients. Our findings might guide the selection of precise targets for effective immunotherapy in the clinic.

Study on data mining of the core syndrome type, pathogenesis and TCM compatibility in ulcerative colitis remission phase / 国际中医中药杂志

Objective:To explore the core syndrome type and Chinese herbal medicine combination in Ulcerative Colitis (UC) remission phase based on the real and effective clinical data of the outpatient information system of the hospital.Methods:Medical records of patients with UC in remission who received Traditional Chinese Medicine (TCM) oral intervention from August 1, 2018 to October 31, 2021 in Jiangsu Provincial Hospital of Traditional Chinese Medicine were collected. Medcase V3.2 data record mining system was used, and the enhanced FPGrowth algorithm was used to build a strengthened association rule data mining model. Xminer Operation Tool was used for mining and logical analysis, and Medcase Chart was used for deconstruction analysis and graphical representation of quantitative trend data. Based on the statistical analysis results, the core syndrome types, pathogenesis evolution rules, and core TCM compatibility law in remission stage of UC were explored.Results:A total of 302 patients were collected. Diarrhea, bloody stool, mucus stool, fatigue, light tongue, fine pulse, paroxysmal abdominal pain, and colonoscopy found intestinal polyps were the core symptoms in UC remission phase. Spleen Qi Deficiency Syndrome, Spleen Deficiency and Dampness Syndrome, Spleen Deficiency and Toxin Accumulation Syndrome were the core syndrome type. In Spleen Qi Deficiency Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Amomi Fructus, Angelicae Sinensis Radix, and Paeoniae Radix Alba. In Spleen Deficiency and Dampness Syndrome, the core drug combinationed Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Poria, Glycyrrhizae Radix et Rhizoma, Aucklandiae Radix, Coptidis Rhizoma, Amomi Fructus, and Saposhnikoviae Radix. In Spleen Deficiency and Toxin Accumulation Syndrome, the core drug combinationed Codonopsis Radix, Astragali Radix, Atractylodis Macrocephalae Rhizoma, Citri Reticulatae Pericarpium, Mume Fructus, Sophorae Flos, Coptidis Rhizoma, and Saposhnikoviae Radix.Conclusion:Spleen deficiency was the core syndrome type in UC remission phase. The Chinese herbal medicine treatment options included replenishing qi supplemented with harmonizing the stomach, promoting blood circulation, stopping bleeding, removing dampness, clearing heat, and relieving depression.

To explore the distribution of TCM syndrome types of refractory tic disorder in children based on cluster analysis / 国际中医中药杂志

Objective:To explore the clinical characteristics and distribution of Tranditional Chinese Medicine (TCM) syndrome types of refractory tic disorders in children based on clustering analysis.Methods:A cross-sectional study. 183 children aged 3-18 years with refractory tic disorders from pediatric encephalopathy outpatient department of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine who met the inclusion criteria from October 2015 to January 2022 were recruited. Frequency descriptive analysis, systematic clustering analysis and principal component analysis were conducted by Microsoft Office Excel 2016 and IBM SPSS Statistics 26.0 to explore the clinical characteristics and syndrome distribution of the disease.Results:The TCM symptoms of 183 children with refractory tic disorders were clustered into 6 categories, and finally 5 types of syndrome were obtained, among which the syndrome of spleen deficiency and liver hyperactivity mixed with dampness accounted for the largest proportion (27.32%), followed by the syndrome of phlegm-fire disturbing spirit (21.31%), the syndrome of wind-heat invading lung (18.03%), the syndrome of phlegm-qi stagnation (17.49%), and the syndrome of dampness and yin deficiency (15.85%).Conclusion:Through the mining and analysis of the outpatient information of pediatric encephalopathy in our hospital, the common syndrome differentiation types of refractory tic disorder are obtained, which can provide a reference for the TCM syndrome differentiation types of refractory tic disorder in children.

Analysis of traditional Chinese medicine syndromes in patients with coronavirus disease 2019 in plateau areas / 中华危重病急救医学

Objective:To analyze the distribution characteristics of traditional Chinese medicine (TCM) syndromes in patients with coronavirus disease 2019 (COVID-19) in plateau areas, and to provide theoretical basis for further clinical treatment of patients with COVID-19.Methods:From August 9 to August 24, 2022, patients with COVID-19 admitted to the Third People's Hospital of Tibet Autonomous Region (designated hospital for COVID-19) were included, and their baseline characteristics (age, gender, source), clinical classification and distribution of TCM syndrome types were collected and analyzed. Data analysis was performed using SPSS 26.0 statistical software.Results:A total of 161 COVID-19 patients were enrolled with ethnic distribution: 124 (77.02%) Tibetans, 35 (21.74%) Han, and 2 (1.24%) Hui, 68 males and 93 females. The male-to-female ratio was 0.73∶1. Aged 1 to 94 years, the average age was (39.06±23.64) years old, of which 4 patients were under 1 year old (excluded because the information was missing). A total of 157 patients were enrolled, and 124 patients (78.9%) were under 60 years old, including 120 cases of common type, 4 cases of severe type, 0 cases of critical type, 7 cases over 80 years old, 1 case over 90 years old, and 32 cases under 18 years old. The clinical manifestations of the patient are mainly cough, expectoration, fever, aversion to cold, dry throat, headache, fatigue, running nose, dry mouth, bitter mouth, etc. Most of the tongue is pale, red, and white greasy moss or thin white coating. In TCM, the most common syndrome was cold-dampness blocking lung syndrome (99 cases, 63.06%), followed by cold-dampness stagnant lung syndrome (22 cases, 14.01%), damp-heat accumulating lung syndrome (22 cases, 14.01%), and humidity stagnant lung syndrome (11 cases, 7.01%). Syndromes of epidemic (2 cases, 1.27%), epidemic toxins blocking the lung pattern (1 cases, 0.64%), toxins with dryness intense heat in both qi and ying phases pattern (0 cases) accounted for less than 2%, and the distribution of various syndrome types in COVID-19 patients was uneven ( χ2 = 0.48, P < 0.05). Conclusion:The most common TCM syndromes of COVID-19 patients in Lhasa are cold-dampness blocking lung syndrome, followed by cold-dampness stagnant lung syndrome, damp-heat accumulating lung syndrome, and humidity stagnant lung syndrome.

Identification of a COL2A1 mutation in a Chinese family with Stickler syndrome type 1 via whole exome sequencing / 中华实验眼科杂志

Objective:To identify the disease-causing mutation in a Chinese family with Stickler syndrome type 1.Methods:The pedigree investigation was conducted.A Chinese family with Stickler syndrome type 1 was enrolled in the Shantou International Eye Center in June 2012.Medical history collection and clinical examinations, such as vision, intraocular pressure, slit lamp microscopy and fundus, were carried out in all the included family members and the diagnosis was made by clinical experts.Total genomic DNAs were extracted from the peripheral blood samples (5 ml) obtained from 5 patients and 4 healthy members.The potential variant of the proband's father Ⅲ-5 were screened by whole exome sequencing (WES) and stepwise bioinformatic analysis.The segregation and mutation conformation of the variant was verified by Sanger sequencing.The pathogenicity of the variant was predicted by SIFT, Polyphen2, and MutationTaster.Conservation and three-dimensional structure of amino acid mutation were analyzed by multiple sequence alignment and UniProt.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Joint Shantou International Eye Center (No.EC20110310[2]-P02).Written informed consent was obtained from each subject or the guardian.Results:An autosomal dominant inherence in 39 members of 4 generations including 15 patients and 24 phenotypically normal members was found in the family.The proband (Ⅳ-4) showed high myopia, retinal detachment and strabismus in the right eye, and the left eye was blind.A patient (Ⅲ-5) showed high myopia and cataract in the right eye, atrophy in the left eye.A patient (Ⅳ-9) showed binocular high myopia.A heterozygous variation, c.1693C>T: p.Arg565Cys, within the exon 26 of COL2A1 gene was revealed in patient Ⅲ-5, which was only found in the patients and not in phenotypically normal members, indiacating co-separation in this family.The variant was predicted to be a severe damage by SIFT, Polyphen2 and MutationTaster.The amino acid mutation at position 565 was highly conservative among human, mouse, rat, bovine and Xenopus laevis, which caused the arginine to cysteine substitution at the X position in triple helix repeat region Gly-X-Y, affecting the function of fibrous protein and becoming pathogenic. Conclusions:Variant c.1693C>T: p.Arg565Cys in COL2A1 gene is disease-causing in this family and this is the first report about the variant in China.

Case report of sphingosine phosphate lyase insufficiency syndrome / 中华实用儿科临床杂志

The data of a child with sphingosine phosphate lyase insufficiency syndrome (SPLIS) admitted to Children′s Hospital of Hebei Province on February 4, 2020 were retrospectively analyzed.The child had edema, complicated with ichthyosis, adrenal calcification, and hearing loss from the early infancy.Laboratory examination results suggested a low albumin level, hypercholesterolemia, a high proteinuria level, abnormal liver and renal functions, and hyponatremia.The child gave up treatment and died at home.Whole Exome Sequencing (WES) results showed two hete-rozygous mutations of SGPL1 gene (chr10: 72604336, c.134G>A, p.W45X; chr10: 72629563, c.719G>T, p.S240I). SPLIS is inherited in an autosomal recessive manner.It starts in infancy, and affects the kidney, skin, endocrine, nervous and immune systems.It is suggested that SPLIS patients should take genetic examination.Early diagnosis, appropriate intervention, and vitamin B 6 treatment may relieve some symptoms of SPLIS patients.Adeno-associated virus mediated SGPL1 gene replacement therapy can be a novel cure of SPLIS and is worthy of investigation.

A pedigree study of Loeys-Dietz syndrome type 4 with skeletal deformity related to a novel TGFβ2 mutation / 中华内科杂志

Objective:Loeys-Dietz syndrome is a rare type of hereditary connective tissue disease. This study was aimed to analyze the clinical characteristics and gene mutations in a family of Loeys-Dietz syndrome with skeletal deformity.Methods:Clinical data of the proband and family members were collected and biochemical measurements and radiological examinations were conducted. Genomic DNA was extracted from peripheral blood of the family members. Whole-exome sequencing was performed to determine the mutation sites in the proband, and Sanger sequencing was applied to verify the candidate mutation in the other family members.Results:The proband is a 34-year-old man with deformities of lower extremities for more than 30 years. Physical examinations showed dolichostenomelia, pes planus, joint laxity and scoliosis. Echocardiography revealed the dilatation of aortic root at the level of the sinuses of Valsalva. A heterozygous missense mutation (c. 220A>C, p.Thr74Pro) in exon 1 of TGFβ2 gene was identified in the proband. The same mutation was detected in his sister and niece with similar clinical features such as deformities of lower extremities and pes planus. This novel mutation has not been reported in ExAC or 1000G and was predicted to be deleterious, supporting a diagnosis of Loeys-Dietz syndrome type 4.Conclusions:Loeys-Dietz syndrome type 4 is caused by TGFβ2 mutations. Skeletal deformity is one of the distinctive features. Genetic testing is helpful for the early diagnosis and differential diagnosis from other connective tissue diseases.

Formulation regularity of traditional Chinese medicine in treatment of sinusitis based on data mining / 中国中药杂志

Based on the Drugdataexpy and the prescription modern application database, this study explored the formulation regularity of ancient and modern prescriptions for the treatment of sinusitis. The Chinese medicinal prescriptions for the treatment of sinusitis with various syndromes were retrieved from the above databases and the corresponding formulation regularity was investigated by frequency analysis, association rule analysis, and factor analysis. Eighty-seven Chinese medicinal prescriptions were included, involving five syndrome types of sinusitis and 160 Chinese medicine, which were mainly effective in releasing exterior, clearing heat, and tonifying deficiency, and acted on the lung meridian due to cold and warm nature and pungent and bitter flavor or on the spleen meridian due to warm nature and pungent flavor. Seventeen core Chinese medicine were screened out by topological data analysis, including Angelicae Dahuricae Radix, Magnoliae Flos, Glycyrrhizae Radix et Rhizoma, Xanthii Fructus, and Scutellariae Radix. Chinese medicine such as Magnoliae Flos, Angelicae Dahuricae Radix, and Xanthii Fructus were commonly used in the treatment of sinusitis of wind-heat in the lung meridian, while the combination of Glycyrrhizae Radix et Rhizoma, Magnoliae Flos, Angelicae Dahuricae Radix, Chuanxiong Rhizoma, etc. was the key compatibility in treating sinusitis of dampness-heat in the spleen and stomach. Six common factors were extracted from the factor analysis of the above two syndrome types. The findings indicate that the exterior-releasing, heat-clearing, and deficiency-tonifying Chinese medicine with cold and warm nature and pungent flavor are preferential options for the clinical treatment of sinusitis. Treatment should be based on syndrome differentiation and key therapeutic principles should be followed.

WANG Ju-yi's meridian diagnosis method combined with Bobath rehabilitation training for post-stroke shoulder-hand syndrome typeⅠ / 中国针灸

OBJECTIVE@#To compare the clinical efficacy differences between WANG Ju-yi 's meridian diagnosis method combined with Bobath rehabilitation training and Bobath rehabilitation training alone for post-stroke shoulder-hand syndrome (SHS) typeⅠ.@*METHODS@#A total of 106 patients with post-stroke SHS typeⅠwere randomly divided into an observation group (53 cases, 2 cases dropped off ) and a control group (53 cases, 3 cases dropped off ). The patients in the both groups were treated with medications for basic diseases and conventional acupuncture at Waiguan (TE 5), Shousanli (LI 10) and Jianyu (LI 15) on the affected side. In addition, the patients in the control group were treated with Bobath rehabilitation training, 20 minutes each time; on the basis of the control group, the patients in the observation group were treated with WANG Ju-yi's meridian diagnosis method to adjust the abnormal parts in meridians of the hand taiyin and hand yangming on the affected side, 20 minutes each time. Both groups were treated once a day, 5 times a week for 8 weeks. The scores of visual analogue scale (VAS), upper-limb Fugl-Meyer assessment (FMA) and Barthel index (BI) were recorded before and after treatment as well as 6 weeks after treatment (follow-up), and the clinical efficacy of the two groups was evaluated after treatment.@*RESULTS@#Compared before treatment, the VAS scores were reduced and the scores of upper-limb FMA and BI were increased in the two groups after treatment and in the follow-up (P<0.05). The VAS score in the observation group was lower than that in the control group (P<0.05), and the scores of upper-limb FMA and BI in the observation group were higher than those of the control group (P<0.05). The total effective rate in the observation group was 82.4% (42/51), which was higher than 62.0% (31/50) in the control group (P<0.05).@*CONCLUSION@#WANG Ju-yi 's meridian diagnosis method combined with Bobath rehabilitation training could effectively treat post-stroke SHS typeⅠ, reduce pain symptoms and improve joint motor dysfunction, and improve the quality of life. Its curative effect is better than Bobath rehabilitation training alone.

Apresentação atípica de síndrome de hiper-IgM ligada ao X simulando doença inflamatória intestinal / Atypical presentation of X-linked hyper-IgM syndrome simulating inflammatory bowel disease

Relatamos o caso de um paciente do sexo masculino, que iniciou quadro de úlceras em trato gastrointestinal, associado a febre recorrente e diarreia com muco e sangue aos 10 meses de vida, suspeitado inicialmente de doença inflamatória intestinal, no entanto, não apresentou melhora do quadro com terapia imunossupressora, sendo realizada investigação para erro inato da imunidade. Nos exames laboratoriais, apresentou níveis baixos de IgG e IgA e níveis elevados de IgM e neutropenia persistente. Diante disso, foi realizado teste genético que confirmou diagnóstico de síndrome de hiper-IgM ligada ao X. Os erros inatos da imunidade podem se manifestar com doenças do trato gastrointestinal, de forma relativamente frequente, devendo entrar como diagnóstico diferencial de diarreia crônica. Inclusa nesse grupo de doenças, as síndromes de hiper-IgM constituem um grupo heterogêneo de doenças, possuindo em comum níveis significativamente baixos ou ausentes de IgG e IgA e níveis normais ou elevados de IgM, o que predispõe a infecções e febre recorrente; além de outras alterações laboratoriais, como neutropenia, que pode estar associada a úlceras no trato gastrointestinal e proctite, simulando apresentação clínica de doença inflamatória intestinal. Para o paciente relatado, foi iniciada terapia com imunoglobulinas de forma periódica, além de antibioticoprofilaxia para infecções, evoluindo com resposta clínica satisfatória. O artigo possui objetivo principal de alertar para o diagnóstico diferencial de erros inatos da imunidade diante do quadro apresentado, visando o diagnóstico precoce e a instituição da terapia adequada.

We report the case of a male patient, who started with ulcers in the gastrointestinal tract, associated with recurrent fever and diarrhea with mucus and blood at 10 months of life, initially suspected of inflammatory bowel disease, however, he did not improve the condition with immunosuppressive therapy, being investigated for inborn error of immunity. In laboratory tests, he had low levels of IgG and IgA and high levels of IgM and persistent neutropenia. Therefore, a genetic test was performed and confirmed the diagnosis of X-linked hyper IgM syndrome. Inborn errors of immunity can manifest relatively frequently with diseases of the gastrointestinal tract, and should be included as a differential diagnosis of chronic diarrhea. Included in this group of diseases, hyper-IgM syndromes constitute a heterogeneous group of diseases, having in common significantly low or absent levels of IgG and IgA and normal or high levels of IgM, which predispose to infections and recurrent fever; in addition to other laboratory alterations, such as neutropenia, which may be associated with ulcers in the gastrointestinal tract and proctitis, simulating the clinical presentation of inflammatory bowel disease. For the reported patient, therapy with immunoglobulins was started periodically, in addition to antibiotic prophylaxis for infections, evolving with a satisfactory clinical response. The main objective of the article is to alert to the differential diagnosis of inborn errors of immunity in view of the presented condition, aiming at early diagnosis and the institution of adequate therapy.

Mutación novel en el Síndrome Sanfilippo B. Presentación de un caso / A novel mutation in Sanfilippo Syndrome type B. Case report

Introducción: El Síndrome Sanfilippo B es un error innato en el metabolismo lisosomal, con herencia autosómica recesiva. Se caracteriza por facie ligeramente tosca, deterioro neurológico progresivo y poca repercusión somática, provocado por mutaciones en el gen NAGLU, cuyo locus es 17q21.2. La incidencia internacionalmente es muy baja y en Cuba solo se han diagnosticado siete pacientes desde 1985. Objetivo: Describir las manifestaciones clínicas, bioquímicas y moleculares de un paciente cubano diagnosticado con Síndrome Sanfilippo B. Presentación de Caso: Se describió un paciente de 13 años, cuyas principales manifestaciones clínicas fueron: facie ligeramente tosca, sinofris, alteraciones de conducta y deterioro neurológico progresivo. El trastorno del sueño fue ocasional y frecuente las infecciones respiratorias. Se demostró la presencia de colitis ulcerativa y pólipo intestinal. Se confirmó excreción aumentada de heparán sulfato y disminución de la actividad enzimática N-acetil αD-glucosaminidasa. Se identificó la mutación c.640dupC en el gen NAGLU en homocigosis en el paciente y ambos padres resultaron ser portadores. Conclusiones: Predominaron las alteraciones de conducta, deterioro neurológico progresivo e infecciones respiratorias en el caso reportado; siendo la colitis ulcerativa y el pólipo intestinal un hallazgo no descrito anteriormente para esta enfermedad. Los estudios cromatográficos y enzimáticos resultaron positivos para Sanfilippo B. El genotipo de este paciente resultó ser homocigótico para una nueva variante alélica patogénica en el gen NAGLU. Se demostró la segregación mendeliana de la mutación en la familia(AU)

Introduction: Sanfilippo syndrome type B is an autosomal recessive lysosomal storage disease. The frequent clinical manifestations include slightly coarse facial features, progressive neurodegeneration and mild somatic repercussion caused by mutations in the NAGLU gene, whose locus is 17q21.2. The worldwide incidence is very low and only seven patients have been diagnosed in Cuba since 1985. Objective: To describe clinical, biochemical and molecular characteristics of a Cuban patient with the diagnosis of Sanfilippo Syndrome type B. Case presentation: A 13 years old patient was described. The main clinical manifestations included mild coarse facie, synophrys, behavior disturbances, and progressive neurologic deterioration. Intermittent sleep disturbance and frequent upper respiratory infections were identified. Ulcerative colitis and intestinal polyp were demonstrated. Increased excretion of heparan sulfate and very low N-acetyl α-Dglucosaminidase activity were confirmed. In addition, the presence of mutation c.640dupC in NAGLU gene was identified. The patient had homozygous genotype and both parents were heterozygous. Conclusions: Behavioral alterations, progressive neurological deterioration and respiratory infections predominated in the reported case. Other findings such as ulcerative colitis and intestinal polyps were not previously described in this disease. The chromatographic and enzymatic studies were positive for Sanfilippo type B. This patient's genotype was found to be homozygous for a novel pathogenic allelic variant in the NAGLU gene. Mendelian segregation of the mutation in the family was demonstrated(AU)

Long non-coding RNA KCNQ1OT1 promotes cell viability and migration as well as inhibiting degradation of CHON-001 cells by regulating miR-126-5p/TRPS1 axis

Abstract Background: Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells. Methods: Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p. Results: Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells. Conclusions: Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.

Application of an extreme learning machine network with particle swarm optimization in syndrome classification of primary liver cancer / 中西医结合学报

OBJECTIVE@#By optimizing the extreme learning machine network with particle swarm optimization, we established a syndrome classification and prediction model for primary liver cancer (PLC), classified and predicted the syndrome diagnosis of medical record data for PLC and compared and analyzed the prediction results with different algorithms and the clinical diagnosis results. This paper provides modern technical support for clinical diagnosis and treatment, and improves the objectivity, accuracy and rigor of the classification of traditional Chinese medicine (TCM) syndromes.@*METHODS@#From three top-level TCM hospitals in Nanchang, 10,602 electronic medical records from patients with PLC were collected, dating from January 2009 to May 2020. We removed the electronic medical records of 542 cases of syndromes and adopted the cross-validation method in the remaining 10,060 electronic medical records, which were randomly divided into a training set and a test set. Based on fuzzy mathematics theory, we quantified the syndrome-related factors of TCM symptoms and signs, and information from the TCM four diagnostic methods. Next, using an extreme learning machine network with particle swarm optimization, we constructed a neural network syndrome classification and prediction model that used "TCM symptoms + signs + tongue diagnosis information + pulse diagnosis information" as input, and PLC syndrome as output. This approach was used to mine the nonlinear relationship between clinical data in electronic medical records and different syndrome types. The accuracy rate of classification was used to compare this model to other machine learning classification models.@*RESULTS@#The classification accuracy rate of the model developed here was 86.26%. The classification accuracy rates of models using support vector machine and Bayesian networks were 82.79% and 85.84%, respectively. The classification accuracy rates of the models for all syndromes in this paper were between 82.15% and 93.82%.@*CONCLUSION@#Compared with the case of data processed using traditional binary inputs, the experiment shows that the medical record data processed by fuzzy mathematics was more accurate, and closer to clinical findings. In addition, the model developed here was more refined, more accurate, and quicker than other classification models. This model provides reliable diagnosis for clinical treatment of PLC and a method to study of the rules of syndrome differentiation and treatment in TCM.

Research progress of clinical and mechanism of Chinese herbal compound on immune recurrent abortion / 国际中医中药杂志

The cause of immune recurrent abortion is closely related to immune abnormalities. At present, the Traditional Chinese Medicine (TCM) syndrome types of immune recurrent abortion mainly include kidney deficiency and blood stasis syndrome, spleen and kidney deficiency syndrome, blood heat syndrome, spleen deficiency syndrome and lung and kidney qi deficiency syndrome; The commonly used TCM compound for treating this disease usually could replenish kidney qi and take effect, so it is considered that the pathogenesis of this disease is mainly kidney deficiency. The mechanism of action of the TCM compound is mainly related to regulating hormone secretion, immune balance and improving local microcirculation.

Distribution of TCM syndrome types and their correlation semen parameters in infertility patients with varicocele / 中华男科学杂志

Objective@#To explore the distribution of Traditional Chinese Medicine (TCM) syndrome types and their relationship with semen parameters in infertility male patients with varicocele (VC).@*METHODS@#Using Questionnaire on Clinical Symptoms of Varicocele-Caused Male Infertility, we made an investigation among 147 infertility male patients with VC, determined the types of their TCM syndromes, obtained their semen parameters, and analyzed the distribution of the TCM syndrome types and their correlation with semen parameters.@*RESULTS@#Of the TCM syndrome types identified, kidney deficiency and stagnated heat constituted the largest proportion (34.7%), and the mixed type accounted for a significantly higher percentage than the simple type (P < 0.05). The patients with kidney deficiency and stagnated heat, compared with those with other syndrome types, had a dramatically lower sperm concentration (［21.62 ± 9.25］ vs ［28.88 ± 12.92］ ×10⁶/ml, P < 0.01), but a higher percentage of morphologically abnormal sperm (［98.33 ± 0.15］% vs ［96.27 ± 0.18］%, P < 0.05) and DNA fragmentation index (［19.72 ± 3.17］% vs ［10.96 ± 3.82］%, P < 0.01). No statistically significant differences were observed in the percentage of progressively motile sperm among different TCM syndrome types.@*CONCLUSIONS@#Kidney deficiency and stagnated heat is a main TCM syndrome type in infertility male patients with varicocele and correlated with sperm concentration, the percentage of morphologically abnormal sperm and DNA fragmentation index.

Effect of Serum from Kidney Yang Deficiency Rats on Expression of β-catenin/OPG/RANKL in OB-OC Co-culture System and Regulatory of Icariin / 中国实验方剂学杂志

Objective:To observe the effect of serum of kidney Yang deficiency rats on the expression of β-catenin，osteoprotegerin(OPG) and nuclear transcription factor-κB receptor activator ligand (RANKL) in the co-culture system and regulatory of icariin on it， and to explore the possible mechanism of inducing osteoporosis.Method:The 16 male SD rats were randomly divided into blank group and model group， 8 rats in each group. 10 mL·kg-1 adenine was administrated to stomach to establish kidney yang deficiency model. Serum was separated and extracted after the model was established successfully. Isolation and culture of osteoblast（OB） and osteoclast（OC） in vitro， OB was observed and identified by alkaline phosphatase（ALP），alizarin red and Giemsa staining， OC was identified by tartrate resistant acid phosphatase（TRAP） staining， OB-OC co-culture system was established in transwell cell， icariin group（100 μmol·L-1）， blank group， icariin（100 μmol·L-1） + serum group， serum group and Dickkopf1（DKK-1） drug（100 μg·L-1） were set up in group ， 2 days after intervention of co-culture system， OC was counted， ALP and TRAP in supernatant were detected by microplate enzyme labeling， and the expression of OPG，β-catenin and RANKL in each group was detected by Western blot.Result:Compared with blank group， the ALP activity，β-catenin and OPG protein expression in serum group were significant reduction （P<0.05）， while the OC quantity， TRAP activity and RANKL protein expression were marked increase （P<0.05）. Compared with serum group， ALP activity of icariin group decreased significantly （P<0.01）， Compared with icariin group， ALP activity and OPG protein expression decreased （P<0.05）， trap activity and RANKL expression increased （P <0.05） in icariin + serum group.Conclusion:The serum of kidney Yang deficiency rats can induce the occurrence of osteoporosis， and the mechanism of action may be through inhibition of ALP activity， down regulating the expression of β-catenin and OPG protein， increasing the activity of TRAP and the expression of RANKL protein.

Relación entre el Síndrome de clase II división 2 y la disfunción temporomandibular. Artículo de revisión / Relation between the Syndrome type II division 2 malocclusions and the temporomandibular joint dysfunction. Review article

Introducción: Los pacientes con el Síndrome de clase II división 2, además de presentar clínicamente una relación de molares y caninos en disto-oclusión, muestran una retroinclinación de los incisivos centrales superiores con proinclinación de los laterales y sobremordida profunda, lo cual puede llegar a convertirse en un factor de riesgo que provoca disfunción temporomandibular. Objetivo: Identificar la relación entre el Síndrome de clase II división 2 y la disfunción temporomandibular. Material y Métodos: Se realizó una revisión bibliográfica automatizada en las bases de datos de los sistemas MEDLINE, PubMed, Hinari y Google; se utilizó un total de 17 artículos. Desarrollo: Por las características clínicas de la oclusión en los pacientes con este síndrome, el rango de movimiento mandibular está limitado, y produce un efecto traumático que se relaciona con una posición de los cóndilos desplazados hacia atrás e intruidos en la fosa glenoidea. Este desplazamiento más distal produce la presión del espacio retrodiscal ricamente inervado y sería causa de inflamación de los tejidos circundantes y afectación de la función de la articulación por elongación de los ligamentos discales o adelgazamiento del disco que afecta el complejo cóndilo-disco. Conclusiones: Los estudios consultados muestran la relación entre el Síndrome de clase II división 2 y la disfunción temporomandibular, dada las características clínicas presentes en este síndrome, que afectan el funcionamiento de la articulación temporomandibular y que al sobrepasar las capacidades adaptativas del paciente producen la disfunción en la misma(AU)

Introduction: Patients with Syndrome type II division 2 malocclusions, besides presenting a clinically established relationship between molars and canines in a distal occlusion, show a retro-inclination of the upper front teeth with pro-inclination of the lateral incisors and a deep overbite, which can result in a risk factor of temporomandibular dysfunction. Objective: To identify the relationship between Syndrome type II division 2 malocclusions and the temporomandibular dysfunction. Material and Methods: A bibliographic review was carried out through a search of databases such as MEDLINE, PubMed, Hinari, and Scholar Google. A total of 17 articles were used. Development: Because of the clinical characteristics of the occlusion in the patients with this syndrome, the range of jaw movement is limited, producing a traumatic effect that is related with a position of the condyles displaced backward and with glenoid fossa intrusion. This more distal displacement produces the pressure of the richly innervated retrodiscal tissue, which could be the cause of inflammation of the surrounding tissues and the affectation of the joint function due to an elongation of the discal ligaments or a thinning of the disc affecting the disc-condyle complex. Conclusions: The studies conducted demonstrate the relationship between the Syndrome type II division 2 and the temporomandibular joint dysfunction, given the clinical characteristics that are present in this syndrome, which affect the functioning of the temporomandibular joint, and produce its dysfunction when exceeding the adaptive capacities of the patient(AU)