Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Objective To summarize the experience of integrative palliative care at Peking Union Medi-cal College Hospital and provide a reference for promoting the integrative palliative care model.Methods Twenty cases receiving integrative palliative care at Peking Union Medical College Hospital were collected.The clinical characteristics,reasons for initiating integrative palliative care,the process of integrative palliative care,and feedback from these cases were summarized.Results Insomnia(11 cases,55％)and pain(9 cases,45％)were the most common symptoms requiring control in the 20 cases.The integrative palliative care team assisted in medical decision-making for 17 cases(85％),prepared end-of-life for 9 cases(45％),assisted in the transfer for 3 cases(15％),and provided comfort care for all the 20 cases(100％).Conclusions The integrative palliative care model can help alleviate suffering in end-of-life patients and provide support to patients'families and the original medical teams.This model is worth further promotion within class A tertiary hospitals.

Objective:To evaluate the role of Kv7.2 in the dorsal root ganglion (DRG) in reduction of paclitaxel-induced neuropathic pain (NPP) by morphine in rats.Methods:SPF healthy male Sprague-Dawley rats, aged 5 weeks, weighing 140-160 g, were randomly selected. This experiment was performed in two parts. Experiment Ⅰ Seventy-two rats were divided into control group (group C), control + morphine group (group C+ M), NPP-1 group (group NPP1) and NPP-1 + morphine group (group NPP1+ M), with 18 animals in each group. Experiment Ⅱ Twenty-four rats were divided into NPP2 group, NPP2+ ML252 group, NPP2+ morphine group (NPP2+ M group), and NPP2 + morphine + ML252 group (NPP2+ M+ ML252 group), with 6 animals in each group. The model of NPP was developed by intraperitoneal injection of paclitaxel 2 mg/kg, once every 2 days for 4 times. After preparation of the model, morphine 5 mg/kg was subcutaneously injected in C+ M group, NPP1+ M group, NPP2+ M group and NPP2+ M+ ML252 group, and potassium channel inhibitor ML252 10 mg/kg was intraperitoneally injected for 7 consecutive days in NPP2+ ML252 group and NPP2+ M+ ML252 group. Six rats were randomly selected from each group on the 1st, 3rd and 7th days after the end of continuous administration in experiment Ⅰ and from each group on the 7th day after the end of continuous administration in experiment Ⅱ for measurement of the mechanical paw withdrawal threshold (MWT) and cold paw withdrawal latency (CWL). At the end of the behavioral assessment, the rats were sacrificed and the DRG was removed for determination of Kv7.2 expression by Western blot. On the 1st day after the end of continuous administration in experiment Ⅰ, the expression of Kv7.2 mRNA in DRG was detected using quantitative real-time polymerase chain reaction, and immunofluorescence was used to detect the co-expression of Kv7.2 with neurons and glial cells in group C.Results:Experiment Ⅰ Compared with C group, the MWT was significantly increased, the expression of Kv7.2 protein and mRNA was up-regulated at each time point ( P<0.05), and no significant change was found in the CWL in C+ M group ( P>0.05), and the MWT was significantly decreased, the CWL was shortened, and the expression of Kv7.2 protein and mRNA was down-regulated at each time point in NPP1 group ( P<0.05). Compared with NPP1 group, the MWT was significantly increased, the CWL was prolonged, and the expression of Kv7.2 protein and mRNA was up-regulated at each time point in NPP1+ M group ( P<0.05). Kv7.2 in DRG was expressed in peptideergic small and medium diameter neurons, non-peptideergic small and medium diameter neurons and large diameter neurons, but not in glial cells. Experiment Ⅱ Compared with NPP2 group, no significant change was found in the expression of MWT, CWL and Kv7.2 in NPP2+ ML252 group ( P>0.05), and the MWT was significantly increased, CWL was prolonged, and the expression of Kv7.2 in DRG was up-regulated in NPP2+ M group ( P<0.05). Compared with NPP2+ M group, the MWT was significantly decreased, CWL was shortened, and the expression of Kv7.2 in DRG was down-regulated in NPP2+ M+ ML252 group ( P<0.05). Conclusions:Down-regulation of Kv7.2 expression in DRG is involved in the reduction of paclitaxel-induced NPP by morphine in rats.

BACKGROUND: Abnormal type I collagen (COL1) expression is associated with the development of many cardiovascular diseases. The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression, but the underlying molecular mechanisms are still not fully understood. METHODS: Gain- and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen (COL1A2). Co-immunoprecipitation assay was performed to observe the interaction between two proteins. RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5. RESULTS: In this study, we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells (VSMCs). We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway. CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta. Mechanistically, circZBTB46 mediates the interaction between Smad2 and PDLIM5, resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression. Furthermore, we found that the expression of TGF-beta and COL1A2 is decreased, while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues, indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development. CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs, highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.

Objective To explore the risk factors for intracranial infection in patients after neurosurgery,con-struct and validate a Nomogram prediction model.Methods Data of 978 patients who underwent neurosurgery in a hospital in Nanjing from January 1,2019 to December 31,2022 were retrospectively analyzed.Independent risk fac-tors were screened through logistic univariate and multivariate analyses.Modeling variables were screened through Lasso regression.A Nomogram model was constructed and internally validated by logistic regression.Effectiveness of the model was evaluated with receiver operating characteristic(ROC)curve,calibration curve and decision curve.Results Among 978 patients underwent neurosurgery,293 had postoperative intracranial infection,with an inci-dence of healthcare-associated infection of 29.96％.There was no significant difference in age,gender,proportion of coronary heart disease,cerebral infarction,diabetes and hypertension between the infected group and the non-in-fected group(all P＞0.05).Multivariate logistic analysis showed that postoperative intracranial hypertension,fe-ver,increased neutrophil percentage in blood routine examination,turbid cerebrospinal fluid,positive Pan's test,decreased glucose concentration,abnormal ratio of cerebrospinal fluid/serum glucose,positive microbial culture,absence of indwelling external ventricular drainage tubes,presence of indwelling lumbar cistern drainage tubes,use of immunosuppressive agents,and long duration of surgery were independent risk factors for postoperative intracra-nial infection in patients who underwent neurosurgery(all P＜0.05).Fifteen variables were screened out through Lasso regression.Fourteen variables were finally included for modeling after collinear screening,missing data impu-tation(random forest method)and checking pairwise interaction items.A Nomogram prediction model was con-structed,with the area under ROC curve,sensitivity,specificity,and accuracy of 0.885,0.578,0.896,and 0.704,respectively.Internal validation of the model was conducted.The modeling and validation groups presented similar effects.The calibration curve and decision curve also indicated that the model had good predictive efficacy.Conclusion The constructed Nomogram prediction model for postoperative intracranial infection after neurosurgery is scientific,and the prediction indicators are easy to obtain.The model presents with high stability,reliability,and application value,thus can provide reference for the assessment of postoperative intracranial infection after neuro-surgery.

Objective: To investigate the effects of high risk factors questionnaire (HRFQ), Asia-Pacific colorectal screening (APCS) score and their combinations with fecal immunochemical test (FIT) in screening advanced colorectal neoplasia, in order to provide an evidence for further optimization of cancer screening program. Methods: A retrospective cohort study method was used to summarize and analyze the results of colorectal tumor screening in Jiashan County, Zhejiang Province from March 2017 to July 2018. Those with severe diseases that were not suitable for colonoscopy and those with mental and behavioral abnormalities who can not cooperate with the screening were excluded. Those who met any one or more of the followings in the HRFQ questionnaire were classified as high-risk people of HRFQ: (1) first-degree relatives with a history of colorectal cancer; (2) subjects with a history of cancer or any other malignant tumor; (3) subjects with a history of intestinal polyps; (4) those with two or more of the followings: chronic constipation (constipation lasted for more than 2 months per year in the past two years), chronic diarrhea (diarrhea lasted for more than 3 months in the past two years, and the duration of each episode was more than one week), mucus and bloody stools, history of adverse life events (occurring within the past 20 years and causing greater trauma or distress to the subject after the event), history of chronic appendicitis or appendectomy, history of chronic biliary disease or cholecystectomy. In this study, those who were assessed as high risk by HRFQ were recorded as "HRFQ (+)", and those who were not at high risk were recorded as "HRFQ (-)". The APCS questionnaire provided risk scores based on 4 risk factors including age, gender, family history and smoking: (1) age: 2 points for 50-69 years old, 3 points for 70 years old and above; (2) gender: 1 point for male, 0 point for women; (3) family history: 2 points for first-degree relatives suffering from colorectal cancer; (4) smoking: 1 point for current or past smoking, 0 point for non-smokers. The population was divided into low-risk (0-1 point), intermediate-risk (2-3 points), and high-risk (4-7 points). Those who were assessed as high risk by APCS were recorded as "APCS (+)", and those with intermediate and low risk were recorded as "APCS (-)". The hemoglobin threshold for a positive FIT was set to 100 μg/L. Those who were assessed as high risk by APCS with positive FIT were recorded as "APCS+FIT (+)". Those who were assessed as high risk by APCS with negative FIT, those who were assessed by APCS as low-middle risk with positive FIT, and those who were assessed by APCS as low-middle with negative FIT were all recorded as "APCS+FIT(-)". Observation indicators in this study were as follows: (1) the screening compliance rate of the cohort and the detection of advanced colorectal tumors; (2) positive predictive value, negative predictive value, sensitivity and specificity of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors; (3) comparison of the detection rate between HRFQ and APCS questionnaire for different colorectal lesions. Using SPSS 21.0 software, the receiver operating characteristic (ROC) curve was drawn to evaluate the clinical value of HRFQ and APCS combined with FIT in screening advanced colorectal tumors. Results: From 2017 to 2018 in Jiashan County, a total of 53 268 target subjects were screened, and 42 093 people actually completed the questionnaire, with a compliance rate of 79.02%. A total of 8145 cases underwent colonoscopy. A total of 3607 cases among HRFQ positive population (5320 cases) underwent colonoscopy, and the colonoscopy compliance rate was 67. 80%; 8 cases were diagnosed with colorectal cancer and 88 cases were advanced colorectal adenoma. A total of 2977 cases among APCS positive population (11 942 cases) underwent colonoscopy, and the colonoscopy compliance rate was 24.93%; 17 cases were diagnosed with colorectal cancer and 148 cases were advanced colorectal adenoma. The positive rate of HRFQ screening was lower than that of APCS [12.6% (5320/42 093) vs. 28.4% (11 942/42 093), χ²=3195. 547, P<0.001]. In the FIT positive population (6223 cases), a total of 4894 cases underwent colonoscopy, and the colonoscopy compliance rate was 78.64%; 34 cases were diagnosed with colorectal cancer and 224 cases were advanced adenoma. The positive predictive values of HRFQ and APCS and their combination with FIT for screening advanced colorectal tumors were 2.67%, 5.54%, 5.44%, and 8.56%; negative predictive values were 94.89%, 96.85%, 96.11% and 96.99%; sensitivity was 29.27%, 50.30%, 12.20 % and 39.02%; specificity was 55.09%, 64.03%, 91.11% and 82.51%, respectively. The ROC curves constructed by HRFQ, APCS, FIT, HRFQ+FIT and APCS+FIT indicated that APCS+FIT presented the highest efficacy in screening advanced colorectal tumors (AUC: 0.608, 95%CI: 0.574-0.642). The comparison of the detection rates of different colorectal lesions between HRFQ and APCS questionnaires showed that there were no significant differences in detection rate of inflammatory polyps and hyperplastic polyps between the two questionnaires (both P>0.05). However, as compared to HRFQ questionnaire, APCS questionnaire had higher detection rates in non-advanced adenomas [26.10% (777/2977) vs. 19.43% (701/3607), χ²=51.228, P<0.001], advanced adenoma [4.97% (148/2977) vs. 2.44% (88/3607), χ²=30.249, P<0.001] and colorectal cancer [0.57% (17 /2977) vs. 0.22% (8/3607), χ²=5.259, P=0.022]. Conclusions: APCS has a higher detection rate of advanced colorectal tumors than HRFQ. APCS combined with FIT can further improve the effectiveness of advanced colorectal tumor screening.
Adenoma/diagnosis* ; Aged ; Asia ; Colonoscopy ; Colorectal Neoplasms/pathology* ; Constipation ; Diarrhea ; Early Detection of Cancer/methods* ; Feces ; Female ; Humans ; Male ; Mass Screening/methods* ; Middle Aged ; Retrospective Studies ; Risk Factors ; Surveys and Questionnaires

Objective: To analyze the clinical and genetic characteristics of 33 children with congenital lipoid adrenal hyperplasia (CLAH) caused by StAR gene defects. Methods: The clinical, biochemical, genetic, and follow-up (until December 2021) data of 33 children diagnosed with CLAH from 2006 to 2021 were retrospectively analyzed in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Results: Of the 33 children with CLAH, 17 had a karyotype of 46, XX and 16 had a karyotype of 46, XY; 31 were female and 2 were male by social gender. Classic type and non-classic type were found in 30 and 3 children respectively. The age at diagnosis was 9.0 (3.0, 34.5) months. All the 30 cases with classic CLAH presented within the first year of life with skin hyperpigmentation (28 cases, 93%), vomiting and(or) diarrhea (19 cases, 63%), no increase in body weight (8 cases, 27%), elevated adrenocorticotropic hormone levels (21cases (70%)>275 pmol/L), decreased cortisol levels (47 (31,126) nmol/L), hyponatremia ((126±13) mmol/L), hyperkalemia ((5.7±1.1) mmol/L), and normal 17α-hydroxyprogesterone levels (30 cases, 100%). All these with classic CLAH exhibited female external genitalia. Three children with non-classic CLAH (including 2 cases of 46, XY and 1 case of 46, XX) also showed signs and symptoms of adrenal insufficiency, but 2 of them had an age of onset later than 1 year of age, including 1 case of 46, XY with male external genitalia and 1 case of 46, XX with female external genitalia. The other 46, XY patient with non-classic CLAH presented with adrenal insufficiency at 2 months of age, showing micropenis and hypospadias. In the 17 females with 46, XX, 4 older than 10 years of age showed spontaneous pubertal development. A total of 25 StAR gene pathogenic variants were identified in 33 patients, with p.Q258* (18/66, 27%), p.K236Tfs*47 (8/66, 12%) and p.Q77* (6/66, 9%) being the common variantion. Six novel variants were found, including c.358T>G, c.713_714del, c.125del, c.745-1G>A, c.179-2A>C, and exon 1 deletion. Conclusions: Patients with classic CLAH typically present with signs and symptoms of primary adrenal insufficiency in the early infancy period and female external genitalia. p.Q258*, p.K236Tfs*47 and p.Q77* are common variants in CLAH patients.
Adrenal Hyperplasia, Congenital/genetics* ; Adrenal Insufficiency ; Adrenocorticotropic Hormone ; Child, Preschool ; China ; Disorder of Sex Development, 46,XY ; Female ; Humans ; Hydrocortisone ; Hydroxyprogesterones ; Hyperplasia ; Infant ; Male ; Mutation ; Phosphoproteins/genetics* ; Retrospective Studies

In this paper， the name， classification， origin and other aspects of Schizonepetae Herba in the famous classical formulas were researched by referring to the related herbal literature， medical books and prescription books in the past dynasties. The results showed that Schizonepetae Herba first appeared in Shennong Bencaojing （《神农本草经》） as Jiasu， while Jingjie first appeared in Wupu Bencao （《吴普本草》）， and the name of Jingjie was mainly used as the rectification of name in later generations. The name of Jiasu is mostly derived from its smell， and the name of Jingjie is mostly derived from its pronunciation. Schizonepeta tenuifolia has been highly praised in the past as a original material， and its genuine producing area is Jiangsu， Hebei and other places， medicinal part is whole herb with spike. In modern times， the quality of Schizonepetae Herba is best described as having thin stems， green spike， and aroma. In clinical application， the raw products of Schizonepetae Herba is mainly used， and the carbonisata is mainly used for hemostasis. Famous classical formulas of Huaihuasan and Danggui Yinzi are all made of Schizonepetae Spica， so it is recommended to use the dried panicle of S. tenuifolia. In Liangxue Dihuangtang， Schizonepetae Herba Carbonisata is used， therefore， it is suggested to adopt the processing method of Schizonepetae Herba Carbonisata in the 2020 edition of Chinese Pharmacopoeia.

Ephedrae Herba is a commonly used medicine for dispersing wind and cold， which has a long medicinal history. By referring to the herbal literature， medical books and prescription books， this paper intends to carry out herbal textual research on the name， origin， medicinal part， producing area， harvesting and processing methods of Ephedrae Herba in famous classical formulas， in order to provide the basis for the development of relevant famous classical formulas. According to textual research， the main base of ancient Ephedrae Herba was Ephedra sinica. The medicinal part is the herbaceous stems of Ephedrae Herba. Before the Northern and Southern dynasties， the origin of the records was Jindi and Hedong， which is now Shanxi province. In the Northern and Southern dynasties and later generations， the producing area expanded， and now it is mainly distributed in Hebei， Shanxi， Shaanxi， Inner Mongolia， Gansu， Liaoning and other places， among which Inner Mongolia is the main producing area. The harvesting and processing methods in the past dynasties are to harvest the stems in autumn， dry them in the shade or air to 70%-80% dry， and then dry them in the sun. The processing methods in the past dynasties mainly include removing the knots， wine-fried， honey-fried， processing with vinegar and so on， at present， only honey-fried is still in use. Based on the research results， it is suggested that Ephedrae Herba in famous classical formulas should be selected the dry herbaceous stems of E. sinica. If the processing requirements are not indicated， it is suggested to use raw products of Ephedrae Herba.

The multi-component pharmacokinetic study of Chinese herbal extracts elaborates the in vivo processes,including absorption,distribution,metabolism,and excretion,of multiple bioactive components,which is of significance in revealing pharmacodynamic material basis of Chinese herbal medicine. In recent years,with the innovation in ideas,and development of techniques and methods on traditional Chinese medicine( TCM) research,the pharmacokinetic studies of Chinese herbal extracts were extensively performed,and notable progress has been made. This paper reviewed the advancement of multi-component pharmacokinetics of Chinese herbal extracts in recent five years from analysis technology of biological sample,the pharmacokinetic characteristics of Chinese herbal medicine with complex system,and the impacts of processing and pathological state on pharmacokinetics of Chinese herbal extracts,aiming to provide a reference for quality control,product development and rational medication of Chinese herbal extracts.
China ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Quality Control