In this paper， by referring to ancient and modern literature， the textual research of Kochiae Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， taste and efficacy， harvesting time， processing and compatibility taboo， so as to provide reference and basis for the development and utilization of related famous classical formulas. According to the investigation， it can be seen that Difuzi was first published in Sheng Nong's Herbal Classic， and has been used as the official name throughout history. It is also known by other names such as Dimai， Dikui， and Luozhou. The mainstream source of Difuzi in materia medica throughout history is the dried ripe fruit of Kochia scoparia， which is consistent throughout history. In the Han dynasty， it was recorded that Kochiae Fructus was produced in Jingzhou（Hubei province）， while modern literature records its distribution throughout the country， so it does not have obvious geoherbalism. The harvesting period of Kochiae Fructus is mostly in the late autumn， and the quality is best when it is full， gray green in color， and no impurities. There are two processing methods for its origin：from the Southern and Northern dynasties to the Ming dynasty， it was dried in the shade， and after the founding of the People's Republic of China， it was dried in the sun. There are few records about the processing of Kochiae Fructus， and its clinical application is mostly based on raw products as medicine. The seedlings are harvested in February of the lunar calendar， and the leaves are taken in April and May， processing in the place of origin is shade drying， the processing methods include burning ash and frying frost， pounding juice and wine soaking. For internal use， it is mostly decocted or mashed， while for external use， it is mostly washed with decoction or taken in a soup bath. Throughout history， it has been recorded that Kochiae Fructus is bitter and cold， and is mainly used for treating bladder fever. After the founding of the People's Republic of China， most of the literature classified it as damp-clearing medicine. Since the 1985 edition of Chinese Pharmacopoeia， it has been recorded that Kochiae Fructus has a pungent and bitter taste， and a cold nature. Returning to the kidney and bladder meridians with functions of clearing heat and dampness， dispelling wind and relieving itching. The clinical contraindications are mainly prohibited for those with deficiency and no dampness and heat. Throughout history， it has been recorded that the taste of the seedlings and leaves is bitter and cold for treatment of dysentery. Since modern times， it has been used to regulate the liver， spleen and large intestine meridians， with functions such as clearing heat and detoxifying， and diuresis. Based on the textual research， it is recommended to use the dried ripe fruit of K. scoparia when developing the famous classical formulas containing Kochiae Fructus， and processing shall be carried out according to the original processing requirements. If the original formula does not specify the processing requirements， the raw products is taken into medicine.

In this paper， by referring to ancient and modern literature， the textual research of Cnidii Fructus has been conducted to clarify the name， origin， distribution of production areas， quality specification， nature and flavour， efficacy， harvesting and processing， compatibility taboo and others， so as to provide reference and basis for the development and utilization of the relevant famous classical formulas. After textual research， it can be verified that Cnidii Fructus was first published in Sheng Nong's Herbal Classic， the materia medica of all dynasties was named Shechuangzi， and there are also aliases such as Shesu， Shemi， and Qiangmi. The main source for generations was the dried ripe fruit of Cnidium monnieri， and ancient and modern consistent. From the Eastern Han dynasty to Tang dynasty， the origin of Cnidii Fructus was Zibo， Shandong province. During the Five dynasties， it expanded to Yangzhou in Jiangsu province and Xiangyang in Hubei province， the Song dynasty added Shangqiu in Henan province， and it was considered that Yangzhou， Xiangyang and Shangqiu were its genuine producing areas. It was more widely distributed in Ming and Qing dynasties. After the founding of the People's Republic of China， the origin is clearly distributed throughout the country. For its quality evaluation， generally full grain， gray yellow color， strong aroma is the best. The harvesting period in the past dynasties was mostly the fifth lunar month， and the fruit was collected to remove impurities and dry. The mainstream processing in producing area of the past dynasties was net selection of raw products， mixing and steaming with the juice of Rehmanniae Radix and stir-frying were the mainstream processing methods in the past， there were also stir-frying with honey， stir-frying with salt and rice wine， immersing and steaming with rice wine and other methods. In recent times， it has been used in raw products as medicine. Sheng Nong's Herbal Classic recorded Cnidii Fructus was bitter， Supplementary Records of Famous Physicians recorded its acrid for the first time. It was recorded in the Ming dynasty that its nature was warm， acted on the kidney meridian， and had small toxicity. After the founding of the People's Republic of China， most of the literature classified it as a medicine to attack poison， kill insects and relieve itching with the functions of dispelling pathogenic wind and removing dampness， destroying parasites and elieving itching， warming kidney and activating Yang. Clinical contraindications are mainly contraindicated for people with damp-heat from the lower-jiao or kidney heat. Based on the textual research， it is suggested that when developing the famous classical formulas containing Cnidii Fructus， the source shall be the dried ripe fruit of C. monnieri， and then it shall be processed according to the original formulas. If there is no requirement for processing in the formulas， the raw products can be taken into medicine.

Humans ; Mpox (monkeypox) ; China

OBJECTIVE: To construct a mouse model of Glanzmann's thrombasthenia (GT) with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation by CRISPR/Cas9 technology, and then further explore the expression and function of glycoprotein αIIbβ3 on the surface of platelet membrane. METHODS: The donor oligonucleotide and gRNA vector were designed and synthesized according to the ITGA2B gene sequence. The gRNA and Cas9 mRNA were injected into fertilized eggs with donor oligonucleotide and then sent back to the oviduct of surrogate mouse. Positive F0 mice were confirmed by PCR genotyping and sequence analysis after birth. The F1 generation of heterozygous GT mice were obtained by PCR and sequencing from F0 bred with WT mice, and then homozygous GT mice and WT mice were obtained by mating with each other. The phenotype of the model was then further verified by detecting tail hemorrhage time, saphenous vein bleeding time, platelet aggregation, expression and function of αIIbβ3 on the surface of platelet. RESULTS: The bleeding time of GT mice was significantly longer than that of WT mice (P<0.01). Induced by collagen, thrombin, and adenosine diphosphate (ADP), platelet aggregation in GT mice was significantly inhibited (P<0.01, P<0.01, P<0.05). Flow cytometry analysis showed that the expression of αIIbβ3 on the platelet surface of GT mice decreased significantly compared with WT mice (P<0.01), and binding amounts of activated platelets to fibrinogen were significantly reduced after thrombin stimulation (P<0.01). The spreading area of platelet on fibrinogen in GT mice was significantly smaller than that in WT mice (P<0.05). CONCLUSION A GT mouse model with ITGA2B c.2659 C>T (p.Q887X) nonsense mutation has been established successfully by CRISPR/Cas9 technology. The aggregation function of platelet in this model is defective, which is consistent with GT performance.
Animals ; CRISPR-Cas Systems ; Codon, Nonsense ; Disease Models, Animal ; Fibrinogen/genetics* ; Humans ; Integrin alpha2/genetics* ; Mice ; Oligonucleotides ; Platelet Glycoprotein GPIIb-IIIa Complex/genetics* ; RNA, Guide ; Thrombasthenia/genetics* ; Thrombin/genetics*

OBJECTIVE: To describe the distribution and trend of infantile epilepsy among infants under 36 months in Ningbo, Zhejiang Province. METHODS: Using the birth cohort design, we retrospectively collected the local born infants in Ningbo national health information platform from 2015 to 2019, and took the first visit of epilepsy in the electronic medical record of the platform as the new case. The incidence density and 95% confidence interval (CI) of epilepsy were estimated by Poisson distribution. RESULTS: From 2015 to 2019, a total of 294 900 children were born in Ningbo, with male accounting for 51.92%. The total person-years of observation were 595 300, while the median follow-up person-years was 2.31 [interquartile range (IQR): 1.90]. There were 575 new onset epilepsy patients during the whole observation period. The total number of visits was 2 599, with an average of 4.52. The total incidence density was 96.59/100 000 person-years (95%CI: 88.85-104.82). The median age of onset was 13 months (IQR: 15), 0-12 months old infants had the highest incidence density (102.18/100 000 person-years), 25-36 months old infants had the lowest incidence density (89.68/100 000 person-years), and the difference was not statistically significant (P>0.05). The incidence density of male was 97.58/100 000 person-years, female was 95.53/100 000 person-years, and the difference was not statistically significant (P>0.05). Fenghua was the highest (130.54/100 000 person-years, 95%CI: 94.47-175.83) and Ninghai was the lowest (66.44/100 000 person-years, 95%CI: 47.02-91. 19), with significant difference (P < 0.05). There was no significant difference in the incidence density in different birth years (P>0.05). There was significant difference in the incidence density between 0-12 months old infants in different calendar years (P_trend < 0.05). In this age group, the incidence density was the lowest in 2015 (69.41/100 000 person-years, 95%CI: 41.79-108.39), and the highest in 2019 (225.61/100 000 person-years, 95%CI: 186.10-271.03). There was no significant difference in the incidence density between 13-24 and 25-36 months old infants in different calendar years (P>0.05). CONCLUSION The incidence density of epilepsy in 0-36 months old infants in Ningbo City from 2015 to 2019 was low as a whole, and there was no difference in age group, gender, and year of birth. The incidence density of 0-12 months old infants increased with the year.
Child, Preschool ; Cities ; Epilepsy/epidemiology* ; Female ; Humans ; Incidence ; Infant ; Infant, Newborn ; Male ; Retrospective Studies

Objective:To investigate the application value of molecular detection in the differential diagnosis of ovarian adult granulosa cell tumors (AGCT) by analyzing FOXL2, AKT1 and DICER1 mutations in these tumors.Methods:A total of 48 cases of ovarian sex cord-stromal tumor (SCST) were selected from July 2012 to June 2019 in Beijing Obstetrics and Gynecology Hospital, including 21 adult granulosa cell tumors (AGCT), 15 fibromas/fibrothecomas, 8 Sertoli-Leydig cell tumors (SLCT) and 4 other types of ovarian SCST. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissue sections. Polymerase chain reaction amplification for FOXL2, AKT1 and DICER1 genes was performed, followed by sequencing using capillary electrophoresis. Fisher exact test was used to compare the prevalence difference of FOXL2, AKT1 and DICER1 mutations among the groups. P<0.05 was considered significant. Results:Eighteen of the 21 (85.7%) AGCT harbored FOXL2 mutation. Compared with other SCST (13.0%, 3 of 23; including fibromas/fibrothecomas and SLCT), FOXL2 mutation was significantly higher in AGCT ( P<0.001). In addition, FOXL2 mutation was also detected in one fibrothecoma, two SLCT and two gynandroblastomas. DICER1 mutation was identified in four of eight SLCT, and these cases were moderately to poorly differentiated. FOXL2 mutation was found in one SLCT with DICER1 mutation. There was no DICER1 mutation in other ovarian SCST. No AKT1 mutation was detected in all the patients. Conclusions:FOXL2 mutation is a highly specific biomarker for adult AGCT and may be helpful to resolve problematic cases. Diagnosis should also be taken into consideration of the clinical and histological features as FOXL2 mutation is also found in other SCST. The detection of DICER1 mutation is helpful for the differential diagnosis of ovarian SLCT. Synchronous DICER1 and FOXL2 mutation in the SLCT has been observed, and its significance needs to be further studied.

Objective: To analyze the prevalence and risk factors of hypertension combined with diabetes in the middle to elder population in the Nan’an district of Chongqing, and to provide evidence for formulating relevant prevention and control strategies. Methods: Middle or elder adults were enrolled by a Stratified multistage cluster sampling method. Questionnaire survey and the related measurements were conducted. The epidemiology of hypertension combined with diabetes was analyzed descriptively, and the risk or protective factors were analyzed by logistic regression method. Results: A total of 24 792 people were surveyed, with 1 547 patients identified as having hypertension combined with diabetes. The overall prevalence rate appeared as 6.2%, of which 6.0% in males and 6.4% in females, respectively. The prevalence of hypertension combined with diabetes in the general population was increasing with age (χ²=343.766, P<0.001). Factors as age, education, smoking, marital status, exercise, BMI, triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol were related to the prevalence of hypertension and diabetes. High density lipoprotein cholesterol appeared as a protective factor for hypertension combined with diabetes (OR=0.817, 95%CI: 0.715-0.934). Age, education, low density lipoprotein cholesterol and lack of exercise all appeared as risk factors for hypertension combined with diabetes (P<0.05), respectively. Conclusions The prevalence rate of hypertension combined with diabetes in the middle or elder adults in Nan’an of Chongqing seemed high. Attention should be paid to the health status of people being elderly, overweight or obese, low cultural level, smoking, triglyceride abnormality, total cholesterol abnormality and high low density lipoprotein cholesterol, so as to reduce the risk on hypertension combined with diabetes.

Xiyanping Injection is a commonly used medicine in clinical treatment,which is recommended by many pediatric disease guidelines/consensus. However,the instraction is relatively simple and lack of guidance for clinical application,which affects the efficacy and brings safety risks. Therefore,more detailed clinical guidance is urgently needed. This consensus is formulated by clinical experts of traditional Chinese medicine and Western medicine in pediatrics. This consensus follows Manual for the clinical experts consensus of Chinese patent medicine which published by China Association of Chinese Medicine. The study identified clinical problems using clinical investigation,searched the literature based on PICO clinical problems,using GRADE system to carry out evidences evaluation,classification and recommendation,and adopted the nominal grouping method to reach expert consensus. The consensus combines evidence-based evidence with expert experience,sufficient evidence of clinical problems would lead to " recommendations",and clinical problems with insufficient evidence will lead to " consensus suggestions". This expert consensus recommends the indications,intervention time for treatment,route of drug administration,dose conversion,the indications of being used alone,suitability and taboos of medicine combination,and introduces the safety and clinical application,to provide reference for clinical using.
Child ; China ; Consensus ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Injections ; Medicine, Chinese Traditional ; Nonprescription Drugs ; Pediatrics

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Objective To analyze and validate the key molecular targets correlated with the overall survival of patients with HER2-positive breast cancer.Methods First,the survival time and transcriptome data of patients with HER2-positive breast cancer in stage Ⅰ / Ⅱ and Ⅲ/Ⅳ were downloaded from the TCGA database.The significantly differential genes between overall survival ＜2 years and ＞8.5 years in stage Ⅰ / Ⅱ were picked out by edgeR package,and the pathways were enriched by KEGG.Similarly,the differential genes between overall survival ＜2 years and ＞7 years in stage Ⅲ/Ⅳ were analyzed.Furthermore,KEGG pathway analysis was performed using the differential genes overlapped by stage Ⅰ /Ⅱ and Ⅲ/Ⅳ.Second,the relationships between the expression levels of key node genes and other genes in enriched pathway and the overall survival of patients with HER2-positive breast cancer were validated by KMplot database.Last,the correlation between the activity of pathway enriched in KEGG and the resistance to anti-HER2 treatment was validated in HER2-positive breast cancer cell line BT474.Results In patients with stage Ⅰ / Ⅱ HER2-positive breast cancer whose overall survival was ＜2 years,PI3K/AKT was the 9th signaling pathway enriched by up-regulated differential genes.In patients with stage Ⅲ/Ⅳ whose overall survival was ＜2 years,PI3K/AKT was the 2nd signaling pathway enriched by up-regulated differential genes.Furthermore,PI3K/AKT was the first signal pathway enriched by the overlapping upregulated genes of patients in stage Ⅰ / Ⅱ and Ⅲ / Ⅳ whose overall survival was ＜2 years.Patients with high expression of PI3K and AKT (key node genes) or CFAP221 and COL4A6 (other genes) of PI3K/AKT pathway had shorter overall survival than those with low expression.PI3K inhibitors could enhance the growth inhibitory effect of HER2 small molecule inhibitor on HER2-positive breast cancer cell line BT474.Conclusions The overexpression of PI3K/AKT pathway is associated with the shorter overall survival in HER2-positive breast cancer patients,and associated with anti-HER2 resistance in HER2-positive breast cancer cell line.