Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Piperis Longi Fructus, made from the mature and immature fruit spikes of Piper longum, is a commonly used Mongolian medicine. In recent years, researchers have gradually deepened the research on ethnic medicines and found that Piperis Longi Fructus has significant effects in adjusting blood lipids and anti-cancer. Its new chemical components and pharmacological activities are also constantly updated. Subsequently, the development and application of Piperis Longi Fructus have attracted extensive attention. Thus, it is quite urgent to establish and improve a quality evaluation system for the medicine. On the basis of summarizing the chemical components and pharmacological effects of Piperis Longi Fructus and understanding the new concept of quality marker(Q-marker), the components which can be used as its Q-markers were analyzed from the aspects of the genetic relationship, traditional medicinal effects and properties, rules of compounding and compatibility, absorbed components and testability. The research can provide reference for the establishment of a quality evaluation system for Piperis Longi Fructus.
Fruit/chemistry* ; Drugs, Chinese Herbal/analysis* ; Biomarkers/analysis* ; Piper

In December 2019, an outbreak of viral pneumonia began in Wuhan, Hubei Province, which caused the spread of infectious pneumonia to a certain extent in China and neighboring countries and regions, and triggered the epidemic crisis. The coronavirus disease 2019(COVID-19) is an acute respiratory infectious disease listed as a B infectious disease, which is managed according to standards for A infectious disease. Traditional Chinese medicine and integrated traditional Chinese and Western medicine have played an active role in the prevention and control of this epidemic. China's ethnomedicine has recognized infectious diseases since ancient times, and formed a medical system including theory, therapies, formula and herbal medicines for such diseases. Since the outbreak of the COVID-19 epidemic, Tibet Autonomous Region, Qinghai Province, Inner Mongolia Autonomous Region, Xinjiang Uygur Autonomous Region and Chuxiong Autonomous Prefecture of Yunnan, Qiandongnan Autonomous Prefecture of Guizhou have issued the prevention and control programs for COVID-19 using Tibetan, Mongolian, Uygur, Yi and Miao medicines. These programs reflect the wisdom of ethnomedicine in preventing and treating diseases, which have successfully extracted prescriptions and preventive measures for the outbreak of the epidemic from their own medical theories and traditional experiences. In this paper, we summarized and explained the prescriptions and medicinal materials of ethnomedicine in these programs, and the origin of Tibetan medicine prescriptions and Mongolian medicine prescriptions in ancient books were studied. These become the common characteristics of medical prevention and treatment programs for ethnomedicine to formulate therapeutic programs under the guidance of traditional medicine theories, recommend prescriptions and prevention and treatment methods with characteristics of ethnomedicine, and focus on the conve-nience and standardization. However, strengthening the support of science and technology and the popularization to the public, and improving the participation of ethnomedicine in national public health services and the capacity-building to deal with sudden and critical diseases are key contents in the development of ethnomedicine in the future.
Betacoronavirus ; China ; Coronavirus Infections ; drug therapy ; Humans ; Medicine, Traditional ; Pandemics ; Pneumonia, Viral ; drug therapy ; Tibet

To analyse the quality of three processed products of Rhizome of Curcuma wenyujin by establishing an ultra performance liquid chromatography (UPLC) method for simultaneously determining five sesquiterpene components in three processed products of rhizome of C. wenyujin and establishing UPLC fingerprints. Component determination was achieved on Waters ACQUITY UPLC BEH C₁₈ column（2.1 mm×50 mm, 1.7 μm), with acetonitrile-water as mobile phase for gradient elution. The flow rate was 0.3 mL·min⁻¹; column temperature was 30 °C; the detection wavelength was set at 214 nm and injection volume was 1 μL. The similarity was analyzed with "Similarity Evaluation System for Chromatographic Fingerprint of Chinese Materia Medica (2012.130723)", and hydrophobic cluster analysis (HCA), principal components analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were conducted by using simca-p14.1 software to investigate the differences in components among these three kinds of processed products. The curzerene, curdione, curcumol, germacrone, furanodiene and β-elemene showed good linearity relationship with chromatographic peak area within the ranges of 10.8-320（=0.999 9）, 10.36-259（=0.998 1）, 10.54-263.5（=0.999 3）, 30.2-755（=0.999 6）and 34.38-862（=0.999 9）mg·L⁻¹, respectively; their average recoveries were 98.75%, 98.69%, 98.63%, 99.76% and 99.57% respectively, with RSD of 2.67%, 1.47%, 1.29%, 2.54% and 0.87% respectively. The similarity of 30 batches of samples was larger than 0.9, indicating good consistency of the samples. The samples can be clearly classified into three categories for HCA, PCA and OPLS-DA pattern recognition, the differential chromatographic peak among three processed products was found respectively. The results showed that the pharmacology basis had changed obviously after processing of Rhizome of C. wenyujin, so it can provide the scientific basis for rational clinical application and establishing quality standards of three processed products of Rhizome of curcuma wenyujin.

To investigate the effect of piperine on the disorder of glucose metabolism in the cell model with insulin resistance (IR) and explore the molecules mechanism on intervening the upstream target of AMPK signaling pathway. The insulin resistance models in HepG2 cells were established by fat emulsion stimulation. Then glucose consumption in culture supernatant was detected by GOD-POD method. Enzyme-linked immunosorbent assay(ELISA) was used to measure the levels of leptin(LEP) and adiponectin(APN) in culture supernatant; Real-time quantitative PCR was used to assess the mRNA expression of APN and LEP; and the protein expression levels of LepR, AdipoR1, AdipoR2 and the activation of AMPK signaling pathway were detected by Western blot analysis. The results showed that piperine, rosiglitazone and AMPK agonist AICAR could significantly elevate the glucose consumption in insulin resistance cell models, enhance the level of APN, promote APN mRNA transcripts and increase the protein expression of Adipo receptor. Meanwhile,AMPKα mRNA and р-AMPKα protein expressions were also increased in piperine treated cells, but both LEP mRNA expression and LepR protein expressions were decreased in piperine treated group. The results indicated that piperine could significantly ameliorate the glucose metabolism disorder in insulin resistance cell models through regulating upstream molecules (APN and LEP) of AMPK signaling pathway, and thus activate the AMPK signaling pathway.

OBJECTIVE The objective of this study was to characterize the neurotransmitter systems that cause constriction of murine airways. METHODS Murine precision cut lung slices (PCLS) and trachea were prepared, placed into perfusion chambers equipped with platinum electrodes and stimulated transmurally (1.0 ms, 50 V, 0.1- 30 Hz). To measure PCLS constriction, changes in airway luminal area in response to electric field stimulation (EFS) were captured as video images quantified using Image J software. For trachea, changes in isometric tension were recorded using Grass force transducers. Frequency response curves were generated in the absence and the presence of the inhibitors magnesium, atropine and capsaicin and responses analyzed and compared using a student' s t- test (P<0.05). RESULTS EFS caused airway constriction in a frequency-dependent manner that was best fit by a biphasic curve. Neuron-specific stimulation was verified by Mg2+ blockade. Maximum airway constriction to 30 Hz EFS in PCLS was (51.8±3.0)% while tracheal constriction averaged (551±80)mg. Interestingly, in PCLS the muscarinic receptor antagonist atropine (10 μmol · L- 1) blocked (99.5 ± 7.2)% of EFS induced constriction at 1 Hz, but only blocked (23.3±3.8)% of EFS induced constriction at 30 Hz and eliminated the first phase but not the second phase of the biphasic EFS response. Treatment with capsaicin to deplete sensory neurotransmitters significantly increased EFS constriction supporting the presence of sensory neurotransmitter systems in airways. CONCLUSION These data are consistent with parasympathetic constriction of airways by acetylcholine at lower EFS frequencies while higher frequencies release sensory dilator neurotransmitters. These data provide evidence for multiple nerve types innervating airways which may provide novel targets for treatment of lung disease.

OBJECTIVE TNF- related apoptosis- inducing ligand(TRAIL)is a promising cancer therapeutic agent due to its minimal toxicity to normal tissues and remarkable apoptotic activity in tumors. However, most breast cancer cells are resistant to TRAIL- induced apoptosis. Our objectives are to investigate the underlying molecular mechanisms and to develop strategies to overcome such resistance. METHODS To identify modulators of TRAIL-induced apoptosis, we carried out a genome wide siRNA screen. To validate the screening result, we either silenced or overexpressed the identified genes in various breast cancer cells and changes in growth and TRAIL-induced cell apoptosis were determined in vitro and in an orthotopic xenograft mouse model. Finally, we investigated whether small molecules targeting the identified genes improve the effectiveness of TRAIL-therapy. RESULTS We unexpectedly identified androgen receptor (AR) to be responsible for TRAIL resistance. While AR is classically viewed as the key factor in prostate cancer progression, we found that AR expression levels were markedly elevated in human invasive breast cancer specimens including triple- negative breast cancers (TNBC) that are highly aggressive with poor prognosis. Importantly, breast cancer cell lines express different levels of AR that correlated with their TRAIL resistance. AR overexpression in MDA- MB- 231 and MDA- MB- 436 cells suppressed the TRAIL sensitivity whereas knockdown of AR rendered MCF-7 and MDA-MB-453 cells sensitive to TRAIL-induced apoptosis. AR overexpression also induced TRAIL resistance in breast tumors in vivo. Further, we observed an upregulation of the TRAIL receptor, death receptor 5 (DR5) in breast cancer cells, following the removal or inhibition of AR by its antagonists Casodex and MDV3100. Treatment with AR antagonists also enhanced TRAIL- induced breast cancer cell apoptosis. CONCLUSION AR signaling suppresses TRAIL-induced breast cancer cell apoptosis, in part, by suppressing DR5 expression, and a combination of AR antagonists together with TRAIL may be a novel and effective therapy for TNBC.

Objective To explore the clinical significance of application of critical patient tracking system in traumatic patient treatment in resuscitation room.Methods A total of 1860 traumatic patients treated in the resuscitation room from September 2013 to August 2014, before critical patients tracking system was applied, were selected as control group, and another 1824 cases, treated from September 2014 to August 2015, after the implementation of this system in resuscitation room of Emergency Department in Yuyao People's Hospital, as observation group. Treatment efficiency, quality, and satisfaction of the patients' relatives were compared between the two groups.Results In the observation group, admission time, rescue time and length of staying in the resuscitation room were (10.00±4.23), (36.70±12.93) and (70.26±24.03) min, shorter than those in the control group [(21.46±11.38), (59.92±22.90), (90.69±25.66) min](P<0.01). Rate of missed diagnosis in the observation group was lower than the control group (2.8% vs. 7.1%), successful rescue rate was higher (97.4% vs. 94.2%), and overall satisfaction of the patients' relatives higher (94.9% vs. 84.5%) (P<0.01). Conclusions Application of critical patient tracking system helps to shorten rescue time of traumatic patients in the resuscitation room, improve treatment effect and satisfactions of the patients' relatives.

Transforming growth factor (TGF)-β signaling plays an important role in the pathogenesis of psoriasis. CD109, a novel TGF-β co-receptor, which inhibits TGF-β signaling by enhancing Smad7-dependent degradation of TGF-β type I receptor (TGF-β RI), is abnormally expressed in psoriasis. To date, the expression of Smad7 and the correlation between CD109 and Smad7 expression in psoriasis have not been fully elucidated. This study was designed to investigate the expression and the correlation of CD109 and TGF-β signaling associated proteins in psoriasis and their roles in the pathogenesis of psoriasis. Thirty-two psoriasis specimens were subjected to immunohistochemical staining for CD109, Smad7, TGF-β RI and Ki67. Ten normal skin (NS) specimens served as controls. The positive expression rate (% positive cells) of Smad7 and Ki67 in psoriasis was significantly higher than in NS (62.6%±19.9% vs. 17.2%±4.4%, and 50.7%±14.3% vs. 19.5%±3.2%, respectively, P<0.001), and the expression levels of CD109 and TGF-β RI were reduced significantly in psoriasis as compared with NS (8.1%±6.7% vs. 35.8%±6.7% and 27.3%±3.4% vs. 3.0%±3.4%, respectively, P<0.001). There were significantly negative correlations between CD109 and Smad7 (r=-0.831, P<0.01). These findings indicated that CD109 might play a certain role in the pathogenesis of psoriasis. Lower expression of CD109 and TGF-β RI was highly correlated with higher expression of Smad7 and Ki67, suggesting that CD109 may induce the pathogenesis of psoriasis through Smad7-mediated degradation of TGF-β RI, and lead to the termination of TGF-β signaling.
Adolescent ; Adult ; Antigens, CD ; genetics ; metabolism ; Case-Control Studies ; Down-Regulation ; Female ; GPI-Linked Proteins ; genetics ; metabolism ; Humans ; Male ; Middle Aged ; Neoplasm Proteins ; genetics ; metabolism ; Psoriasis ; metabolism ; pathology ; Signal Transduction ; Smad7 Protein ; genetics ; metabolism ; Transforming Growth Factor beta ; metabolism ; Up-Regulation