BACKGROUND:Intestinal acute graft-versus-host disease is one of the most aggressive complications after allogeneic hematopoietic stem cell transplantation with high lethality.How to improve intestinal inflammation and regulate autophagy by applying traditional Chinese medicine in order to treat intestinal acute graft-versus-host disease is a worthwhile research issue nowadays. OBJECTIVE:To investigate the mechanism of Huangqintang modulating intestinal flora for the treatment of intestinal acute graft-versus-host disease. METHODS:CB6F1 mice were irradiated with 60Co X radiation at a total dose of 8 Gy,and then single nucleated cell suspensions(bone marrow cells+splenocytes)from Balb/c H-2d mice were injected into the tail vein in order to prepare a model of intestinal acute graft-versus-host disease.These samples were randomly divided into the model group and the high-,moderate-,and low-dose Huangqintang groups.After modeling,the model,high-,moderate-,and low-dose groups received different doses of Huangqintang or an equal volume of saline by continuous gavage for 14 days.Clinical acute graft-versus-host disease grading,and survival time was recorded.Small intestinal tissues from each group were stained with hematoxylin and eosin for small intestinal mucosal pathology scoring.The intestinal flora of mice in each group was detected using 16S rDNA sequencing.Autophagy-related markers were detected using immunofluorescence,immunohistochemistry,and PCR. RESULTS AND CONCLUSION:(1)Compared with the model group,the survival time of mice was significantly prolonged(P<0.01);the clinical acute graft-versus-host disease scores were significantly reduced(P<0.01);the pathological grading scores of the small intestinal mucosa were significantly diminished(P<0.01);the levels of the small intestinal tissue inflammatory factors tumor necrosis factor-α,interleukin-1β,and interleukin-6,were significantly decreased(P<0.01);the structural integrity of the small intestinal mucosal epithelium was partially restored in mice after the intervention of moderate and high-dose Huangqintang.(2)The study of intestinal flora found that compared with the model group,the pro-inflammatory strain Enterococcus was significantly reduced(P<0.05),while beneficial bacteria such as Clostridium_innocuum and Rhodococcus,a pro-autophagy bacterium,were significantly elevated(P<0.05)in the moderate-dose Huangqintang group.(3)Compared with the model group,the autophagy markers were significantly elevated in the moderate-dose Huangqintang group(P<0.05);under transmission electron microscopy,the number of autophagic vacuoles of moderate-dose Huangqintang group increased significantly.(4)The results showed that Huangqintang significantly reduced the abundance of conditionally pathogenic bacteria and the level of inflammatory factors in small intestinal tissues,and increased the relative abundance of beneficial bacteria and promoted the expression of autophagy in the small intestinal mucosa,which resulted in a significant improvement of intestinal symptoms in mice with acute graft-versus-host disease.

Diabetic retinopathy （DR） is one of the most common chronic microvascular complications of diabetes mellitus. It has a high rate of blindness， and the age of onset is gradually getting younger， which seriously affects the physical and mental health and quality of life of patients. The disease is retinal damage induced by diabetes mellitus， which is a kind of fundus disease with the main manifestations of fundus hemorrhage， hard exudation， microhemangioma， cotton-wool spots， neovascularization， etc. In traditional Chinese medicine （TCM）， it is classified into the category of "diabetic cataracts" and other diseases. At present， there is no effective method to prevent the progress of the disease in modern medicine， so it is particularly important to choose a reasonable and effective intervention to prevent and treat DR. Studies have confirmed that TCM has unique advantages in the treatment of DR. It can use its advantages of multiple bioactive components， multiple targets， and multiple pathways to intervene in the development process of DR from various aspects. By searching for the relevant literature on the progress of the intervention of DR with TCM monomers and compounds， this paper mainly reviews the relevant research results of the treatment of DR with multiple signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， nuclear factor kappa-B（NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， nuclear factor erythroid 2-related factor （Nrf2）/hemeoxygenase-1 （HO-1）， Hippo， advanced glycation end products （AGEs）/receptor for advanced glycation end products （RAGE）， and Akt/glycogen synthase kinase-3β （GSK-3β）， so as to provide more ideas and directions for the clinical prevention and treatment of DR.

Objective:To improve clinicians′ understanding of developmental and epileptic encephalopathy (DEE) caused by PPP3CA gene mutation. Methods:Clinical data of a patient with DEE diagnosed in the First Department of Neurology, Hebei Children′s Hospital in September 2018 were collected. The whole-exome sequencing of the proband′s family was performed, and the characteristics of gene mutation were analyzed. Literature review was carried out based on the reported cases related to PPP3CA gene. Results:The proband, a 3 months and 20 days old girl, was admitted to the hospital with a history of paroxysmal confusion with extremities shaking for 2 days. The clinical manifestations included frequent epilepsy seizures and hypoevolutism. Brain magnetic resonance imaging showed that the bilateral frontotemporal extracerebral space was slightly wider. The video electroencephalography showed hyperarrhythmia and a cluster of spastic seizures. Whole exome sequencing of the family revealed that the proband had a heterozygous de novo frameshift truncating mutation in the PPP3CA gene: c.1255-1256delAG (p.Ser419Cysfs*31). From the establishment of the database to May 2022, 8 foreign literatures and 1 Chinese literature were retrieved, and a total of 21 children with PPP3CA gene mutation were reported, with clinical developmental delay, cognitive dysfunction and abnormal electroencephalography activity. Conclusions:The frameshift truncating mutation of the PPP3CA gene (c.1255-1256delAG) is the hereditary etiology of this patient. For cases of frequent seizures with poor efficacy of antiepileptic drugs, and developmental delay, genetic testing should be performed to confirm diagnosis and treatment.

Objective:To summarize the clinical manifestations and color Doppler ultrasonography of benign lymphoepithelial disease (BLL) in lacrimal gland, so as to improve the diagnostic accuracy of lacrimal BLL.Methods:Clinical manifestations and color Doppler flow imaging (CDFI) features of lacrimal BLL in 16 patients (2 males and 14 females, with 31 lesions) who visited the Second Hospital of Hebei Medical University from November 2014 to August 2019 were retrospectively analyzed.Results:The performance for lesions in patients with duration less than 3 months was scattered in irregular low echo, lesion blood flow signals within the rich (Adler Ⅱ level), pathologic examination results showed more lymphocytes were seen in the lacrimal matrix, and the myoepithelium of the lacrimal duct grew to form the epithelium-myocutaneous island. The ultrasonic feasures in patients with course of 3-6 months were in multiple categories such as circular low echo, "honeycomb" change, CDFI showed lesions with a lot of blood flow signals (Adler Ⅲ level), the pathological examination results indicated that there were a large number of lymphocytes and epithelial-musculocutaneous islands in the lacrimal matrix, and the lymphocytes were significantly increased compared with patients with the course of disease less than 3 months. The ultrasound results in patients with a course of more than 6 months showed lesions in multiple categories such as circular low echo, and large low echo, greater than 3 mm in diameter, CDFI showed lesions within the same large amounts of blood flow signals (Adler Ⅲ level), the pathological examination results were consistent with the course of 3 to 6 months. One patient had positive tuberculin test and 11 had higher IgG4 than normal.The number of lymphocytes increased with the prolongation of disease course.Conclusions:With the expert knowledge of color Doppler ultrasonographic characteristics of lacrimal gland BLL and with the serum IgG4 level helps to improve the accuracy of ultrasonic diagnosis.

Objective:To summarize the clinical features and treatment of voltage-gated sodium channel α2-subunit (SCN2A) gene-related epilepsy.Methods:The clinical manifestion, video electroencephalography, head magnetic resonance imaging of a child diagnosed with epilepsy in Hebei Children′s Hospital were analyzed. Additionally, blood samples of the family were tested for the whole exome sequencing.Results:The boy aged 20 months,had been developed backward since childhood and accompanied by autism spectrum disorder manifestations. Seizures occurred at 19 months, manifested as isolated and clusters of spasms or generalized tonic seizures. The whole exome sequencing of the family revealed that the proband had c.4543C>T heterozygous mutation in the SCN2A gene, and both parents showed wild type. The effect of multiple anti-epileptic drugs on the children was not good, but the epilepsy was controlled after the final addition of perampane.Conclusions:The c.4543C>T heterozygous variant of SCN2A gene is the cause of disease in this child. This variant can cause epilepsy with autism spectrum disorder. The location and type of SCN2A mutations are strongly related with phenotypes, and a clear genetic etiology contributes to accurate treatment of children.

Objective:To investigate the pathogenic characteristics of viral encephalitis or meningitis in children living in Shijiazhuang city and surrounding areas, and to study the relationship between pathogenic and clinical findings.Methods:A total of 132 cerebrospinal fluid specimens were randomly collected from hospitalized children diagnosed with viral encephalitis or meningitis (January 2018 to December 2018) in the Department of Neurology of Hebei Children′s Hospital in Shijiazhuang city and surrounding areas. The nucleic acids of four viruses in cerebrospinal fluid were detected by real-time quantitative PCR. SPSS 21.0 software was used for statistical analysis.Results:Among the 132 cases, 78 were boys and 54 were girls, with a sex ratio of 1.44∶1. However, in the gender composition of children in each age group, there was no significant difference (χ 2=3.901, P=0.272). Of the 132 children, 121 had signs of fever, 109 had symptoms of headache, 92 had symptoms of vomiting, 17 had abnormal electroencephalogram(EEG), and 15 had abnormal head magnetic resonance imaging(MRI). 132 cerebrospinal fluid specimens were tested for pathogenic pathogens, and 80 of them were successfully detected. There was 1 case of human herpesvirus type I(HHV-I), 2 cases of varicella-zoster virus (VZV) and 77 cases of enterovirus(EV). The age group of 1~3 years′s EV detection rate was 66.67%, it is the highest, but overall, the EV detection rate, there was no significant difference among the four age groups (χ 2=3.147, P=0.369). The detection rate of EV in summer and autumn were 65.52% and 70.83%, respectively, which were significantly higher than those in spring and winter (33.33% and 0.00%), and there was a significant difference (χ 2=22.504, P=0.000). There was no significant difference in the positive rates of fever, headache and vomiting between EV-positive and non-EV-positive children ( P>0.05). There was no significant difference in the incidence of abnormal EEG and abnormal head MRI between EV-positive and non-EV-positive children ( P>0.05). Conclusions:In 2018, EV was the main pathogen of viral encephalitis and meningitis in children in Shijiazhuang city and surrounding areas, and EV detection rate was high in summer and autumn.

Objective:To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome.Methods:The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children′s Hospital and Hebei Children′s Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms "MOCS2" "molybdenum cofactor deficiency" "Leigh-like syndrome,MOCS2" "molybdenum cofactor deficiency, Leigh-like syndrome". The phenotypes and genotypes of MoCD-B were summarized.Results:A 7 months and 14 days old boy with the chief complaint of "cough for 6 days, abnormal posture for 4 days and fever for 2 days" was admitted to Hebei Children′ Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support.Conclusions:Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis.

Objective:To analyze the surgical methods of operable breast cancer and analyze the follow-up results.Methods:A retrospective analysis of the clinical and pathological data of 636 operable breast cancer patients admitted to Zibo First Hospital from July 2008 to April 2018, including the clinical stage, pathological staging. Analyze of the proportion of four surgical methods, and through follow-up, analyze the treatment effect of different surgical methods.Results:All patients are female, aged 26-80 years, the clinical stage of 636 patients: Tis 18 cases, stage Ⅰ 143 cases, stage Ⅱ 354 cases, stage Ⅲ 114 cases, stage Ⅳ 7 cases. There are four types of surgery: ① breast conserving surgery + sentinel lymph node biopsy in 124 cases (19.50%); ② breast conserving surgery + axillary lymph node dissection in 39 cases (6.13%); ③ mastectomy + sentinel lymph node biopsy in 163 cases (25.63%); ④ modified radical surgery in 310 cases (48.74%). Sentinel lymph node biopsy in 427 cases (67.14%), success in 404 patients (94.61%); all patients with lymph node negative 384 cases (60.38%). Follow-up for 1 to 9 years, 11 cases of local recurrence after breast-conserving surgery, It accounted for 6.75% of breast-conserving surgery; 43 cases of local recurrence of chest wall after mastectomy, accounting for mastectomy 9.09%; 33 cases of recurrence and metastasis of axillary lymph nodes and supraclavicular lymph nodes, 4 cases of axillary recurrence after sentinel lymph node biopsy.Conclusions:The proportion of breast-conserving surgery in this group of patients was high and the local recurrence rate of breast-conserving surgery was less than that of mastectomy group; the proportion of simple modified radical surgery declined further; patients with axillary lymph node metastasis were less in the whole group. The choice of reasonable operation method is an important factor to improve the prognosis of breast cancer.

Objective:To investigate the expression level and significance of peripheral lymphocyte immunity and humoral immunity in children with autoimmune encephalitis and children with mycoplasma encephalitis.Methods:From July 2018 to July 2019, 52 children with autoimmune encephalitis (autoimmune encephalitis group) and 68 children with mycoplasma encephalitis (mycoplasma encephalitis group) in Hebei Children′s Hospital were enrolled, and 43 children with mycoplasma infection who were treated at the same time were selected as control group. Serum immunoglobulin (IgA, IgG, IgM) levels were detected using a fully automated biochemical analyzer, and peripheral T-lymphocyte subsets (CD 3+, CD 4+, CD 8+, CD 4+/CD 8+) levels were measured using flow cytometry. The receiver operating characteristic (ROC) curve was used to analyze the clinical differential diagnostic value of serum immunoglobulin and T lymphocyte subsets indicators for autoimmune encephalitis and mycoplasma encephalitis. Results:The levels of serum IgA, IgM in three groups had significant differences ( P<0.05); the levels of serum IgA, IgM in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(1.64 ± 0.56) g/L vs. (1.23 ± 0.48),(0.82 ± 0.25) g/L; (1.81 ± 0.45) g/L vs. (1.56 ± 0.48), (1.12 ± 0.34) g/L]( P<0.05); the level of IgG in three groups has no significant difference ( P>0.05). The levels of CD 4+,CD 8+ in mycoplasma encephalitis group were significantly higher than those in autoimmune encephalitis group and control group [(31.21 ± 3.86)% vs. (28.76 ± 3.57)%, (26.58 ± 3.49)%; (26.86 ± 1.89)% vs. (25.90 ± 2.16)%, (24.71 ± 2.46)%]( P<0.05); the level of CD 4+/CD 8+ in three groups has no significant difference ( P>0.05). The areas under the curve of serum IgA, IgM, CD 3+, CD 8+, CD 4+ and five combined diagnosis were 0.971, 0.835, 0.833, 0.631, 0.706 and 1.000. The optimal critical values were 1.255 g/L, 1.465 g/L, 57.435%, 26.456%, 29.750% and 1.858. The sensitivity was 100.0%, 64.7%, 95.6%, 92.6%, 69.1% and 100.0%, and the specificity was 95.6%, 57.0%, 57.1%, 23.4%, 36.4% and 100.0%. Conclusions:The expression levels of serum IgA, IgM and peripheral serum CD 3+, CD 4+ and CD 8+ in children with autoimmune encephalitis are significantly lower than those in children with mycoplasma encephalitis, and IgA, IgM, CD 3+, CD 8+ and CD 4+ has high differential diagnosis value.

Objective: To explore the status quo and influencing factors of psychological stress in pregnant women in the third trimester, and to propose reasonable intervention measures to improve their current situation, and to provide reference and guarantee for their smooth transition through pregnancy. Methods: A questionnaire survey was conducted to investigate 92 pregnant women in the second trimester of pregnancy from the Second Affiliated Hospital of Wenzhou Medical University from June 2017 to June 2018 by using questionnaires, quality of life and stress scales.The results of the survey were investigated and analyzed. Results: The survey showed that the average psychological stress score of pregnant women in the third trimester was (1.79±0.46)points.The main stressors were psychological pressures to protect the health of pregnant women and the safety of the fetus.The planned pregnancy was the influencing factor of psychological stress (F=2.456, P=0.015). The negative life events and subjective support and stressors 1, 2, 3, etc.as independent variables, the results showed that stress source 2, positive life events and anxiety were the main influencing factors of patients' psychological stress (t=6.874, 3.692, 2.754, all P<0.05). Conclusion The psychological stress status of pregnant women in the third trimester is moderate, and the planned pregnancy is the influencing factor.The main psychological stress is to protect the health of the pregnant woman and the safety of the fetus.Therefore, the clinical counseling can be actively carried out in the clinic and the intervention of pregnant women's psychology should be strengthened to alleviate the bad mood and relieve psychological stress.