This article systematically reviews and verifies the name， origin， production area， quality evaluation， harvesting， processing and other aspects of Cynanchi Atrati Radix et Rhizoma（CARR） by consulting relevant ancient and modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. Through textual research， Baiwei has been the official name for CARR， though it also bears alternative names such as Chuncao， Popo Zhenxianbao， Longdan Baiwei. The mainstream base is the roots and rhizomes of Cynanchum atratum. Historical records indicate primary producing areas include Shandong， Anhui， Jiangsu， Shaanxi and Shanxi. Since the late Ming dynasty， varieties from Juxian， Yishui and Rizhao in Shandong have been highly regarded as authentic， commonly known as eastern Baiwei. Since modern times， its quality has been summarized as fine， slender， and straight fibrous roots， pale yellow exterior， whiter interior， and dryness with easy breakability are considered superior. The harvesting time before the Song dynasty was on the third day of the third lunar month， but after the Song dynasty， harvesting was possible in both spring and autumn. The initial processing methods of CARR in ancient times included drying in the shade， removing Lu（the little rhizomes which are on tap of roots）， and removing mustaches， modern methods involve washing and sun-drying. During the Northern and Southern dynasties， processing methods included steaming. In the Song dynasty， drying and light stir-frying were predominant， while wine washing emerged in the Ming dynasty. Modern practices primarily involve using raw， stir-frying or honey processing. Regarding the medicinal properties of CARR， both ancient and modern texts agree it has a bitter and salty taste and is non-toxic. Records prior to the Qing dynasty predominantly describe its nature as extremely cold， while mainstream herbal texts after the Qing dynasty generally characterize it as cold. Before the Ming dynasty， there were no records of its meridian tropism. It was not until the Qing dynasty that it was recorded in the lung meridian. Modern records mainly refer to the stomach， liver， and kidney meridians. Throughout history， its main functions have been to clear heat， diuresis， nourish Yin， and replenish essence， primarily treating Yin deficiency and fever syndrome. Based on the research results， it is suggested that when developing famous classical formulas containing CARR， the dried roots and rhizomes of C. atratum can be selected as its medicinal source. If there are no specific processing requirements， raw products can be selected as medicine. If the processing requirements are specified， corresponding processed products can be selected as medicine according to the original formula requirements.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

This article systematically analyzes the historical evolution of the name， origin， medicinal parts， producing area， harvesting and processing， nature， flavor and efficacy of Piperis Longi Fructus by referring to the materia medica， medical books， and prescription books of past dynasties， combined with the relevant modern literature， in order to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the herbal textual research， the name of Piper longum first appeared in Nanfang Caomuzhuang， and it also has other aliases such as Biboli， Halou， and Hujiaohua. Historically， the origin of Piperis Longi Fructus has been P. longum of the Piperaceae family. In ancient times， both the fruit and root were used as medicine， and since the Republic of China， the fruit has been mainly used as medicine. The medicinal part is the dried， nearly ripe or ripe fruit spikes. Piperis Longi Fructus is native to India and has been introduced into China since the Tang dynasty. In the Ming dynasty， Bencao Pinhui Jingyao clearly stated that the genuine producing area was "Duanzhou"， present-day Zhaoqing in Guangdong province. Nowadays， it is planted in Guangdong， Guangxi， Hainan， Yunnan and other regions. Historically and currently， harvesting occurs in autumn. The ancient processing method uniformly involved removing the stems， soaking in the sourest vinegar overnight， baking， and scraping off the peels and grains with a knife until clean. In modern times， impurities are removed， and it is dried in the sun and crushed when used. The properties， functions and applications of P. longum are basically the same in ancient and modern times. It tastes pungent， is warm in nature， and non-toxic. It has the effects of warming the middle-jiao to dispel cold， lowering Qi and relieving pain， and is used for cold pain in the epigastrium and abdomen， vomiting， diarrhea， chest pain， headache， and toothache. Based on the research results， it is recommended that when developing famous classical formulas containing Piperis Longi Fructus， the dried nearly ripe or ripe fruit spikes of P. longum should be used. If there are no clear processing requirements， it is recommended to use the raw products for medicinal use， and the specific processing methods can refer to the relevant requirements under Piperis Longi Fructus in the 2025 edition of the Pharmacopoeia of the People's Republic of China. If processing requirements such as soaking in vinegar and peeling are clearly specified， it is recommended to follow the ancient methods.

ObjectiveTo investigate the efficacy and safety of cinobufagin tablets combined with thalidomide/dexamethasone （TD） regimen in the treatment of newly diagnosed multiple myeloma （NDMM） with phlegm and stasis obstruction. MethodsThe clinical data of 50 patients with NDMM of phlegm and stasis obstruction who were hospitalized at the Jiangsu Province Hospital of Chinese Medicine from June 1st， 2015 to July 31th， 2019 were retrospectively analyzed， and they were divided into a control group （bortezomib/dexamethasone-containing regimen， 27 cases） and an observation group （cinobufagin tablets combined with TD regimen， 23 cases）. The clinical efficacy and safety were compared between the two groups after two or three courses of treatment. The primary outcomes were clinical remission rate including overall response rate and deep remission rate， one-year and two-year overall survival rate， and adverse effects. The secondary outcomes were the proportion of plasma cells in bone marrow， hemoglobin， β2-microglobulin， lactate dehydrogenase， serum creatinine， blood urea nitrogen， bone pain score， and KPS functional status score （KPS score） before and after treatment. ResultsIn terms of clinical efficacy， there was no statistically significant difference （P＞0.05） in the overall response rate ［the observation group 69.57%（16/23） vs the control group 70.37% （19/27）］ and deep remission rate ［the observation group 56.52% （13/23） vs the control group 55.56% （15/27）］ between groups after the treatment. The one-year overall survival rates of the observation group and the control group were 90.9% and 92.4%， and the two-year overall survival rates were 81.8% and 80.9% respectively， with no statistically significant differences between groups （P＞0.05）. During the treatment， no renal function injury occurred in both groups. The incidence of peripheral nerve injury in the observation group was 8.70%， which was lower than 48.15% in the control group （P＜0.01）. After the treatment， the proportion of myeloma plasma cells， β2-microglobulin， serum creatinine level， and bone pain score decreased， while the hemoglobin level and KPS score increased in both groups （P＜0.05 or P＜0.01）. Compared between groups after treatment， the bone pain score of the observation group was lower than that of the control group， while the KPS score was higher than that of the control group （P＜0.05）. ConclusionThe clinical efficacy of cinobufagin tablets combined with TD in the treatment of NDMM is equivalent to bortezomib/dexamethasone-containing regimen， but the former is more helpful in relieving the pain and improving the quality of life， and has better safety.

Objective To explore the clinical and genetic characteristics of 17α-hydroxylase/17,20-lyase deficiency(17OHD)in childhood.Methods The clinical features,laboratory and imaging examination results,gene mutation characteristics of 4 children diagnosed with 17OHD in Children's Hospital Affiliated to Zhengzhou University from January 2016 to December 2022 were retrospectively analyzed,and the literature was reviewed and summarized.Results At the time of diagnosis,the age of 4 children ranged from 11 months and 21 days to 10 years and 6 months.All patients had karyotypes of 46,XY.Social gender:1 male and 3 females.The chief complaints were 1 case of short penis,1 case of inguinal mass,and 2 cases of grade 2 hypertension,and 3 cases of testes were found in scrotum,groin and inguinal annulus,respectively.The levels of cortisol,testosterone,and androstenedione decreased at 8 o'clock in 4 children,while the levels of adrenocorticotropic hormone,progesterone,luteinizing hormone,and follicle stimulating hormone increased.17 hydroxyprogesterone was normal.Mild decrease in blood potassium levels(3.44-3.48 mmol/L)was found in 3 cases.One case of CYP17A1 homozygous mutation and three cases of compound heterozygous mutation were found,among which c.563 A＞G and c.436+1G＞T were new mutation sites that had not been reported in the past,and 3 cases had c.985_987delinsAA mutation.All 4 cases received oral hydrocortisone treatment.Conclusions Abnormal external genitalia,inguinal/labial mass and hypertension are the main features of 46,XY type 17OHD in childhood.Early hydrocortisone replacement therapy can effectively prevent the complications of 17OHD.The CYP17A1 c.985_987delinsAA mutation may be a hot topic mutation in children with 17OHD in China.

Objective:To explore the clinical and genetic characteristics of three children with Leguis syndrome.Methods:Three children suspected as Legius syndrome at the Henan Children′s Hospital for precocious puberty or short stature from June 6, 2019 to August 25, 2022 were selected as the study subjects. Clinical data of the children were collected. All children were subjected to whole exome sequencing, and candidate variants were verified by Sanger sequencing.Results:All of the children (including 2 females and 1 male, and aged 4 years and 6 months, 8 years, and 14 years and 8 months, respectively) had typical café de lait spots. Child 1 also had precocious puberty, and children 2 and 3 had short statures. Genetic testing revealed that all of them had harbored heterozygous variants of the SPRED1 gene, including c. 751C>T (p.Arg251Ter194) in child 1, c. 229A>T (p.Lys77Ter368) in child 2, and c. 1044_1046delinsC (p.R349fs *11) in child 3. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the c. 751C>T (p.Arg251Ter194) variant was predicted to be likely pathogenic, whilst the other two were known pathogenic variants. Conclusion:All of the three children were diagnosed with Leguis syndrome due to variants of the SPRED1 gene, which had manifested as multiple café de lait spots in conjunct with precocious puberty or short statures.

Objective To investigate the relationship between serum leucine-rich a-2 glycoprotein-1(LRG1),transforming growth factor-β1(TGF-β1)and the carotid intimal middle layer thickness(IMT)and short-term poor prognosis in acute cerebral infarction(ACI).Methods A total of 123 patients with ACI who were treated in Guangji Hospital of Suzhou from January 2020 to January 2023 were selected,and the patients were divided into normal group(23 cases),thickened group(30 cases)and plaque group(70 cases)according to the IMT,and 35 healthy physical examiners in Guangji Hospital of Suzhou during the same period were se-lected as the health control group,and the serum LRG1,TGF-β1 levels and IMT of 4 groups were compared.The patients were followed up for 3 months and divided into good prognosis group(75 cases)and poor prog-nosis group(48 cases)according to the prognosis.The correlation between serum LRG1,TGF-β1 and IMT was analyzed by Pearson method.Univariate and multivariate Logistic regression were used to analyze the risk factors of short-term poor prognosis in ACI patients.The receiver operating characteristics(ROC)curve was used to analyze the predictive value of serum LRG1 and TGF-β1 for the short-term poor prognosis of ACI.Re-sults The serum LRG1 level in health control group,normal group,thickened group and plaque group in-creased sequentially,and TGF-β1 level decreased sequentially(P＜0.05).Pearson correlation analysis showed that serum LRG1 was positively correlated with IMT,while TGF-β1 was negatively correlated with IMT(P＜0.05).Age,proportion of patients with diabetes,the National Institutes of Health Stroke Scale(NIHSS)score at admission,low-density lipoprotein cholesterol(LDL-C),fasting plasma glucose(FPG),white blood cell count(WBC),C-reactive protein(CRP)and serum LRG1 levels in the poor prognosis group were higher than those in the good prognosis group(P＜0.05),time from onset to thrombolysis was longer than that in the good prognosis group(P＜0.0.05),while the serum TGF-β1 level was lower than that in the good prognosis group(P＜0.05).Multivariate Logistic regression analysis showed that high NIHSS score,long time from onset to thrombolysis,elevated serum LRG1 level and decreased TGF-β1 level were risk factors for short-term poor prognosis in ACI patients(P＜0.05).ROC curve results showed that the area under the curve of the sin-gle and combined detection of serum LRG1 and TGF-β1 for predicting the short-term prognosis of ACI pa-tients were 0.824,0.708 and 0.902,respectively.Conclusion ACI patients have elevated serum LRG1 levels and decreased TGF-β1 levels.Serum LRG1 and TGF-β1 levels are closely related to the IMT and the short-term prognosis of ACI patients,and the combined detection of serum LRG1 and TGF-β1 levels have high ref-erence value for predicting the short-term poor prognosis of ACI patients.

Objective:To analyze and determine the clinical and genetic characteristics of children with Helsmoortel-Van der Aa syndrome(HVDAS).Methods:Clinical data of 6 children with HVDAS treated at the First Hospital of Peking University from November 2018 to October 2022 and their family members were collected and analyzed retrospectively.Whole exome sequencing was performed on children and their family members to identify the genetic variants.Genotype and phenotype correlation was analyzed.Results:(1) Clinical analysis results: among the 6 children, there were 5 boys and 1 girl, and their age at diagnosis ranged from 11 months and 17 days to 12 years and 9 months.Six patients all presented with developmental delays/intellectual disabilities; (2) Genetic analysis results: 6 de novo ADNP variants were discovered in 6 children, including 1 initial codon deletion variant c. 1_2del, 2 nonsense variants c. 1175dup, p.(Tyr392*) and c. 2213C>G, p.(Ser738*), and 3 frameshift variants c. 2632dup, p.(Ser878Lysfs*3), c.1695_1696insATGGTATGTATGTATGTATG, p.(Val566Metfs*8) and c. 2120_2123del, p.(Asn707Serfs*8).All variants were classified as pathogenic variants by the American College of Medical Genetics and Genomics.Except the c. 2213C>G, p.(Ser738*), the other 5 variants are all novel variants that have not been reported before. Conclusions:All of the 6 cases of HVDAS showed typical clinical manifestations, and expanded the phenotype spectrum of microcephaly and tall stature.Six de novo mutations were discovered, expanding the ADNP mutation spectrum and providing accurate genetic counseling and prenatal genetic diagnosis of the disease.

Atrial fibrillation (AF) is one of the most common arrhythmias. Studies have shown that there is a significant correlation between inflammation and AF. Pathogenic microbial infection has long been considered the most likely factor to trigger and maintain the inflammatory process. In recent years, with the development of molecular biology technology, more and more evidence shows that some bacteria and viruses can cause AF. The research on AF and pathogens has gradually become a hot topic in recent years.