Objective:To evaluate the impact of three small compounds, namely sodium diethyldithiocarbamate (DTC), levamisole (LMS) and imiquimod (Imi), on the immunogenicity and protective efficacy of the candidate antigen PA0833 from Pseudomonas aeruginosa ( Pa) and analyze the underlying mechanisms. Methods:PA0833 was formulated with aluminum adjuvant and the above small compounds, respectively. BALB/c mice were immunized with these vaccines intramuscularly on days 0, 14 and 21. Serum samples were collected and the levels of PA0833-specific IgG were measured by ELISA. The protective efficacy of these vaccines was evaluated by assessment of survival rates, body weights, clinical scores, inflammatory factors, and histopathological changes after infecting the immunized mice with Pa PAO1 strains. Besides, the mice were injected with DTC intramuscularly for seven consecutive days to analyze the mechanism of DTC in enhancing immune response using transcriptome sequencing and flow cytometry. Results:All these small compounds were capable of effectively enhancing the immunogenicity of PA0833 formulated with aluminum adjuvant, reducing bacterial loads in lung tissues, inhibiting the secretion of TNF-α, IL-6 and IL-1β, and improving mouse survival rates upon Pa infection. DTC was more effective than the other two compounds. Transcriptome sequencing identified 121 up-regulated genes and 18 down-regulated genes in DTC-treated group as compared with PBS control group. These differentially expressed genes were significantly enriched in immune pathways, with a strong activation of the IL-17 pathway. Flow cytometry analysis demonstrated significant activation of dendritic cells and proliferation of Th17 cells in splenocytes in DTC-treated group as compared with PBS control group. Conclusions:All three small compounds are able of effectively enhance antigen immunogenicity with DTC being the most effective, indicating that DTC can be used as a novel adjuvant in vaccine development.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.

OBJECTIVE: To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS). METHODS: Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing. RESULTS: Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons. CONCLUSION The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.
DNA Copy Number Variations ; Facies ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Zinc Finger E-box Binding Homeobox 2/genetics*

OBJECTIVE: To analyze the clinical and genetic characteristics of a child with clinical manifestations of hypoplasia, epilepsy and abnormal face. METHODS: The clinical data of the child were collected. The peripheral blood samples of the patient and his parents were extracted for high-throughput sequencing, and Sanger sequencing verification and bioinformatics analysis were performed to detect suspected pathogenic variants. RESULTS: The clinical manifestations of the child were overall developmental backwardness, seizures, autism, and special facial appearance. High throughput sequencing showed that there was a heterozygous mutation of exon 11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) of the DYRK1A gene. The same variant was found in neither of her parents, suggesting that it has a denovo origin. CONCLUSION The exon11: c.1920_c.1927delCCTCTACC (p.Ser641Rfs*31) mutation in DYRK1A gene was the genetic etiology of the case, which enriches the pathogenic gene spectrum of DYRK1A and provides the basis for clinical diagnosis and genetic counseling.
Arthrogryposis ; Child ; Facies ; Female ; Heterozygote ; Humans ; Intellectual Disability/genetics* ; Mutation

Shenling Baizhusan is a traditional Chinese medicine compound prescription formulated on the basis of Si Junzitang （Ginseng Radix et Rhizoma， Atractylodis Macrocephalae Rhizoma， Poria， Glycyrrhizae Radix et Rhizoma）. It has excellent functions of replenishing Qi， invigorating spleen， draining dampness， and checking diarrhea， and is one of the classical prescriptions of ''reinforcing earth to generate metal''. This prescription is primarily used in clinical practice to treat malnutrition in children， chronic diarrhea， gastrointestinal dysfunction， and other disorders. In addition， it has a good effect on gastrointestinal adverse reactions associated with radiotherapy and chemotherapy. With the booming of molecular biology， researchers have revealed the role of Shenling Baizhusan in the treatment of diseases， especially the mechanism of regulating different signaling pathways. We retrieved 26 relevant papers （4 written in English and 22 in Chinese） published in recent 5 years from 6 databases including China National Knowledge Infrastructure （CNKI）， Wanfang Data， VIP， PubMed， Cochrance Library， and Excerpta Medica Database （Embase）. On the basis of these papers， we summarized the mechanisms of Shenling Baizhusan in disease treatment. In the animal model of inflammatory bowel disease， Shenling Baizhusan can protect gastrointestinal mucosa by regulating the activation of nuclear factor kappa-B （NF-κB）， mitogen-activated protein kinase （MAPK）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， and myosin light chain kinase-myosin light chain （MLCK-MLC） signaling pathways. In the animal model of non-alcoholic fatty liver disease， Shenling Baizhusan regulates the activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin （PI3K/Akt/mTOR） signaling pathway and Kelch-like ECH-associating protein 1/NF-E₂-related factor 2/advanced glycation end-products （KEAP1/NRF2/AREs） signaling pathway， thus alleviating the lipid metabolism disorder induced by high-fat diet and reducing liver lipid accumulation and inflammatory response. In the animal model of lung cancer with bone metastasis， Shenling Baizhusan regulates the activation of PI3K/Akt/mTOR signaling pathway， thus playing an analgesic role. By summarizing the mechanisms of Shenling Baizhusan in treatment of different disease models from signaling pathways， we aim to provide clues for the in-depth study of this prescription.

The clinical data of a child with anti-(α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid, AMPA2) receptor antibody encephalitis after herpes simplex encephalitis was retrospectively analyzed.The child was a 9-year-old female developing abnormal mental behavior after fever.The auxiliary examination of the first hospital displayed, cerebrospinal fluid: sugar qualitative (+ ), white blood cell count 32×10 6/L, albumin measurement (immune turbidity method) 317.00 mg/L, immunoglobulin IgG 45.80 mg/L.Herpes simplex virus (+ ). Skull magnetic resonance imaging showed: abnormal signal at the top of the frontal frontotemporal, considering intracranial infection.Video electroencephalogram: the background is diffuse slow wave, a small amount of multifocal spikes, sharp waves, spine slow wave release, left frontal, and temporal sacral protrusions.One partial seizure may be detected during the awake period.The diagnosis was " herpes simplex virus encephalitis" , and the body temperature of the child returned to normal after anti-infection and hormone therapy.However, there were still cognitive impairments, irritability, and no language communication.After 2 years, there was no abnormality in routine biochemical and viral cerebrospinal fluid examination.Serum and cerebrospinal fluid autoimmune encephalitis-related antibody spectrum: anti-NMDA, AMPA1/2, GABAB receptor antibody and anti-CASPR2, LGI1 antibodies were negative in serum.The anti-AMPA2 receptor antibody in the cerebrospinal fluid was weakly positive, and the final diagnosis was anti-AMPA2 receptor antibody encephalitis.After the application of hormones, the children′s cognition improved, mood was more stable than before, and language communication improved as well.Anti-AMPA2 receptor antibody encephalitis can be observed in children, and may be related to immune response after viral infection.For patients of viral encephalitis with poor treatment or disease relapse and progression, the possibility of autoimmune encephalitis should be considered.

The clinical data of a child with paroxysmal kinesigenic dyskinesia (PKD) and being diagnosed and treated in the Department of Pediatrics of the First Affiliated Hospital of Zhengzhou University in October 2018 were analyzed retrospectively.The male patient was 13 years old.The clinical manifestation was the change of body position, and the temporary movement cannot appear.The manifestations included the turning of head to one side, the falling back of neck, head shaking, swinging, the tightly hugging of hands in front of the chest, the touching of two tiptoes to the ground, numb sole, and ache.Gene detection: chromosome 16p11.2 (chr16: 29594293-30189789) had about 595.5 kb heterozygosity deletion.A total of 8 cases of 16p11.2 microdeletion in children with PKD were reported in details.16p11.2 microdeletion is another form of gene expression that causes PKD.16p11.2 microdeletion should be screened for genetic evaluation in patients with PKD.

Objective:To observe the effect of hair care products containing zinc pyrithione, pollen extract, sachitin and other ingredients assisted with finasteride in the treatment of androgenic alopecia.Methods:From June 2018 to February 2019, 60 male androgen alopecia patients aged 18-40 (30.85±4.73) years were enrolled in this study. 30 cases in each group were treated for 180 days, and finasteride 1 mg/day was taken orally in both groups. In the experimental group, on the basis of finasteride, hair care products containing zinc pyrithione, pollen extract, sachitin and other ingredients were used, while the control group was treated with common care products. The improvement of scalp and hair and the satisfaction of patients were evaluated before and after treatment.Results:After 180 days of treatment, the improvement of scalp oil ( t=2.744, P<0.05), pruritus ( t=2.574, P<0.05), dandruff ( t=2.579, P<0.05) and general sense of use ( t=2.134, P<0.05) in the experimental group were significantly better than those in the control group ( t=2.077, P<0.05). The hair density of the experimental group was significantly better than that of the control group ( P<0.05). The patients＇ satisfaction rates in the experimental group and the control group were 96.67% (29/30) and 83.33% (25/30), respectively; there was no significant difference between the two groups ( P>0.05). No adverse reactions were found in all patients. Conclusions:Hair care products containing zinc pyrithione, pollen extract, sachitin and other ingredients assisted with finasteride can improve the scalp oil, pruritus and dandruff of patients with androgenic alopecia, and can increase the curative effect of the treatment of alopecia of the patients.