Zhusha Anshenwan is a classical traditional Chinese medicine （TCM） formula originating from LI Dongyuan's Treatise on the Differentiation of Endogenous and Exogenous Injuries （Nei Wai Shang Bian Huo Lun） of the Jin-Yuan period. It is composed of five medicinal ingredients： Cinnabaris （Zhusha）， Coptidis Rhizoma （Huanglian）， Angelicae Sinensis Radix （Danggui）， Rehmanniae Radix （Shengdihuang）， and Glycyrrhizae Radix et Rhizoma （Gancao）. Under the guidance of TCM theory， this formula is used to treat syndromes of disturbed spirit， including insomnia， palpitations， and anxiety， caused by hyperactivity of heart fire and deficiency of Yin-blood， and it also exerts auxiliary anticonvulsant effects in epilepsy and related conditions. However， the potential neurotoxicity， hepatotoxicity， and nephrotoxicity of its monarch drug， Cinnabaris （mainly composed of mercuric sulfide， HgS）， together with the risk of in vivo accumulation， have rendered its clinical application controversial， and it has not yet been formally included in the Pharmacopoeia of the People's Republic of China. In addition， restrictions imposed by the Minamata Convention on Mercury have led to an increasing shortage of natural medicinal Cinnabaris resources， making the evaluation of the efficacy and safety of synthetic Cinnabaris particularly urgent. This contradiction highlights the complexity of safety evaluation for traditional medicines. Existing studies indicate that Zhusha Anshenwan exhibits definite pharmacological activities in calming the mind， improving sleep， and regulating emotional disorders. Moreover， other components of the formula may exert antagonistic effects on the toxicity of Cinnabaris， and reports of severe mercury poisoning caused by standardized clinical use of this prescription are extremely rare. Research suggests that other ingredients in the compound formula， such as Rehmanniae Radix， Coptidis Rhizoma， and Glycyrrhizae Radix et Rhizoma， may effectively alleviate the hepatorenal toxicity of Cinnabaris through mechanisms including modulation of the gut microbiota， formation of mercury complexes， and direct protection of target organs. This article aims to systematically review the progress in pharmacodynamic research on Zhusha Anshenwan， to explore its mechanisms of action in depth， and to analyze the toxicokinetic characteristics and safety risks of Cinnabaris， as well as the scientific connotations of toxicity reduction and efficacy enhancement achieved through compound compatibility. In addition， it compares Zhusha Anshenwan with other commonly used sedative formulas， with the aim of providing a scientific basis and forward-looking perspectives for the safe and rational application and in-depth development of this classical prescription in a modern context， and of emphasizing the important value of holistic research on TCM compound formulas in addressing the challenges of single-component toxicity.

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.
Humans ; Female ; Blood Platelets/pathology* ; Biomarkers, Tumor/genetics* ; Ovarian Neoplasms/pathology* ; China

Humans ; Female ; Deep Learning ; Ovarian Neoplasms/genetics* ; Carcinoma, Ovarian Epithelial/genetics* ; Neural Networks, Computer ; RNA

OBJECTIVES: To investigate the clinical characteristics, pathological features, treatment regimen, and prognosis of children with lupus nephritis (LN) and thrombotic microangiopathy (TMA), as well as the treatment outcome of these children and the clinical and pathological differences between LN children with TMA and those without TMA. METHODS: A retrospective analysis was conducted on 12 children with LN and TMA (TMA group) who were admitted to the Department of Nephrology, Children's Hospital of Nanjing Medical University, from December 2010 to December 2021. Twenty-four LN children without TMA who underwent renal biopsy during the same period were included as the non-TMA group. The two groups were compared in terms of clinical manifestations, laboratory examination results, and pathological results. RESULTS: Among the 12 children with TMA, 8 (67%) had hypertension and 3 (25%) progressed to stage 5 chronic kidney disease. Compared with the non-TMA group, the TMA group had more severe tubulointerstitial damage, a higher Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score at onset, and higher cholesterol levels (P<0.05). There were no significant differences between the two groups in the percentage of crescent bodies and the levels of hemoglobin and platelets (P>0.05). CONCLUSIONS There is a higher proportion of individuals with hypertension among the children with LN and TMA, as well as more severe tubulointerstitial damage. These children have a higher SLEDAI score and a higher cholesterol level.
Child ; Humans ; Lupus Nephritis/complications* ; Kidney/pathology* ; Retrospective Studies ; Thrombotic Microangiopathies/therapy* ; Prognosis ; Hypertension/complications* ; Cholesterol ; Lupus Erythematosus, Systemic

Objective: To clarify the molecular basis of patients with Bartter syndrome type I and explore the therapeutic effect of trafficking-defective variations by chemical chaperone 4-Phenylbutyric acid(4-PBA). Methods: The clinical characteristics, laboratory findings and genetic data of 3 patients diagnosed with Bartter syndrome type I who were admitted to Department of Nephrology, Children's Hospital of Nanjing Medical University from 2017 to 2018 were retrospectively analyzed. Wild type and variant SLC12A1 gene constructs were transiently overexpressed in HEK293 cells. Western blotting was used to detect the expression levels of Na⁺-K⁺-2Cl^-cotransporter(NKCC2) protein. Immunofluorescent staining was applied to investigate the subcellular localization of NKCC2 protein. In addition, the effect of the chemical chaperone 4-PBA on the expression and localization of the SLC12A1 gene variants was investigated. Unpaired t test was used for statistical analysis of 4-PBA treatment. Results: All the 3 patients (2 males and 1 female), aged 3.0, 4.0 and 1.2 years, respectively. All patients had antenatal onset with polyhydramnios and were born prematurely. After birth, all patients presented with hypochlorine alkalosis accompanied by hypokalemia and hyponatremia. Sequencing analysis revealed that the 3 patients were homozygotes or compound heterozygotes for variants in the SLC12A1 gene. In HEK293 cells, the surface expression of NKCC2 in 3 variants (p.L463S, p.L479V, p.507-510del) are all lower than in wild type (0.718±0.039, 0.287±0.081, 0.025±0.156 vs. 1.001±0.028, t=5.92, 8.35, 30.49, all P<0.01). Moreover, the total protein expression of p.L479V and p.507-510del group were all lower than that in wild type group (0.630±0.032, 0.043±0.003 vs. 1.000±0.111, t=3.21, 8.65, all P<0.05). 4-PBA treatment increased the mature protein expression level of the p.L463S and p. L479V group in 4-PBA treatment group are all higher than the untreated group (0.459±0.018 vs. 1.123±0.024, 0.053±0.012 vs. 1.256±0.037, t=2.75, 18.35, all P<0.05). Cytoplasmic retention of the L479V and 507-510del variants were observed by immunofluorescent staining. 4-PBA treatment could rescue a number of NKCC2 L479V variants to the membrane. Conclusions: The 3 SLC12A1 variants cause expression or subcellular localization defects of the protein. The findings that plasma membrane expression and activity can be rescued by 4PBA might help to develop novel therapeutic strategy for Bartter syndrome type Ⅰ.
Bartter Syndrome/genetics* ; Child, Preschool ; Female ; HEK293 Cells ; Homozygote ; Humans ; Infant ; Male ; Pregnancy ; Retrospective Studies ; Solute Carrier Family 12, Member 1/genetics*

Objective::To assess the clinical features of fetal growth restriction (FGR) in women with hypertensive disorders of pregnancy in China.Methods::This is a retrospective cohort study. The clinical data of 4 451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015. The mean maternal age was (31.0±5.4) years old. Participants were divided into FGR group ( n= 670) and non-FGR group ( n= 3 781). The incidence and clinical features of FGR, and its correlation with gestational age, previous FGR history, 24-hour urinary protein excretion, and hemolysis, elevated liver enzyme and low platelet count (HELLP) syndrome were analyzed. Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups. Results::The overall incidence of FGR was 15.1% (670/4 451). The FGR incidence was 22.4% (433/1 937) in women with severe preeclampsia and 18.6% (68/365) in women with chronic hypertension with superimposed preeclampsia, respectively. FGR was more prevalent in women who had preterm births than those who had term births (22.8% (432/1 898) vs. 9.3% (238/2 553), P < 0.001). It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia (18.4% (189/1 025) vs. 14.0% (481/3 426), P= 0.001). Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history (66.7% (4/6) vs. 15.7% (250/1 596), P= 0.007). The presence of abnormal results of the umbilical artery Doppler (13% (87/670) vs. 2.4% (89/3 781), P < 0.001) and the middle cerebral artery Doppler (3.3% (22/670) vs. 0.4% (15/3 781), P < 0.001) was higher in the FGR group compared with the non-FGR group, while the presence of increased uterine artery resistance was not statistically different (1.5% (10/670) vs. 0.8% (29/3 781), P= 0.072). The FGR group delivered earlier than the non-FGR group ((35.3±3.0) weeks vs. (36.4±4.3) weeks, P < 0.001) with lower birth weight (1 731.0±574.5) g vs. (2 753.9±902.1) g, P < 0.001, higher fetal or neonatal death (9.4% (63/670) vs. 4.2% (157/3 781), P < 0.001), and higher cesarean section rate (82.5% (553/670) vs. 70.2% (2 656/3 781), P < 0.001). In the FGR group, more neonates had 5-minute Apgar score ≤7 (7.9% (53/670) vs. 3.9% (149/3 780), P < 0.001), with higher neonatal intensive care unit admission rate (48.1 % (322/670) vs. 23.3% (881/3 781), P < 0.001). More cases of HELLP syndrome occurred in the FGR group (6.9% (46/670) vs. 3.2% (122/3 781), P < 0.001). Women with FGR had heavier 24-hour urinary protein excretion than those without FGR ((3.9±3.7) g vs. (3.1±4.2) g, P= 0.005). Conclusion::In pregnancies with hypertensive disorders, increased risks of FGR are associated with preterm birth, birth before 34 weeks, and a previous FGR history. FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler. When hypertensive disorders is complicated by FGR, there appears to be higher maternal morbidity including higher rate of HELLP syndrome, cesarean section, and heavier proteinuria, as well as worse neonatal outcomes.

Objective::To assess the clinical features of fetal growth restriction (FGR) in women with hypertensive disorders of pregnancy in China.Methods::This is a retrospective cohort study. The clinical data of 4 451 women with hypertensive disorders of pregnancy were retrospectively collected from 11 tertiary hospitals across ten provinces in China during January 2015 to December 2015. The mean maternal age was (31.0±5.4) years old. Participants were divided into FGR group ( n= 670) and non-FGR group ( n= 3 781). The incidence and clinical features of FGR, and its correlation with gestational age, previous FGR history, 24-hour urinary protein excretion, and hemolysis, elevated liver enzyme and low platelet count (HELLP) syndrome were analyzed. Student’s t-test and Chi-square test were used when comparing clinical features between FGR and non-FGR groups. Results::The overall incidence of FGR was 15.1% (670/4 451). The FGR incidence was 22.4% (433/1 937) in women with severe preeclampsia and 18.6% (68/365) in women with chronic hypertension with superimposed preeclampsia, respectively. FGR was more prevalent in women who had preterm births than those who had term births (22.8% (432/1 898) vs. 9.3% (238/2 553), P < 0.001). It was also more prevalent in women with early-onset preeclampsia than those with late-onset preeclampsia (18.4% (189/1 025) vs. 14.0% (481/3 426), P= 0.001). Women with a previous FGR history had a significantly higher FGR incidence than those without an FGR history (66.7% (4/6) vs. 15.7% (250/1 596), P= 0.007). The presence of abnormal results of the umbilical artery Doppler (13% (87/670) vs. 2.4% (89/3 781), P < 0.001) and the middle cerebral artery Doppler (3.3% (22/670) vs. 0.4% (15/3 781), P < 0.001) was higher in the FGR group compared with the non-FGR group, while the presence of increased uterine artery resistance was not statistically different (1.5% (10/670) vs. 0.8% (29/3 781), P= 0.072). The FGR group delivered earlier than the non-FGR group ((35.3±3.0) weeks vs. (36.4±4.3) weeks, P < 0.001) with lower birth weight (1 731.0±574.5) g vs. (2 753.9±902.1) g, P < 0.001, higher fetal or neonatal death (9.4% (63/670) vs. 4.2% (157/3 781), P < 0.001), and higher cesarean section rate (82.5% (553/670) vs. 70.2% (2 656/3 781), P < 0.001). In the FGR group, more neonates had 5-minute Apgar score ≤7 (7.9% (53/670) vs. 3.9% (149/3 780), P < 0.001), with higher neonatal intensive care unit admission rate (48.1 % (322/670) vs. 23.3% (881/3 781), P < 0.001). More cases of HELLP syndrome occurred in the FGR group (6.9% (46/670) vs. 3.2% (122/3 781), P < 0.001). Women with FGR had heavier 24-hour urinary protein excretion than those without FGR ((3.9±3.7) g vs. (3.1±4.2) g, P= 0.005). Conclusion::In pregnancies with hypertensive disorders, increased risks of FGR are associated with preterm birth, birth before 34 weeks, and a previous FGR history. FGR is related to higher occurrence of abnormal uterine artery Doppler and umbilical artery Doppler. When hypertensive disorders is complicated by FGR, there appears to be higher maternal morbidity including higher rate of HELLP syndrome, cesarean section, and heavier proteinuria, as well as worse neonatal outcomes.

BACKGROUND: An artificial intelligence system of Faster Region-based Convolutional Neural Network (Faster R-CNN) is newly developed for the diagnosis of metastatic lymph node (LN) in rectal cancer patients. The primary objective of this study was to comprehensively verify its accuracy in clinical use. METHODS: Four hundred fourteen patients with rectal cancer discharged between January 2013 and March 2015 were collected from 6 clinical centers, and the magnetic resonance imaging data for pelvic metastatic LNs of each patient was identified by Faster R-CNN. Faster R-CNN based diagnoses were compared with radiologist based diagnoses and pathologist based diagnoses for methodological verification, using correlation analyses and consistency check. For clinical verification, the patients were retrospectively followed up by telephone for 36 months, with post-operative recurrence of rectal cancer as a clinical outcome; recurrence-free survivals of the patients were compared among different diagnostic groups, by methods of Kaplan-Meier and Cox hazards regression model. RESULTS: Significant correlations were observed between any 2 factors among the numbers of metastatic LNs separately diagnosed by radiologists, Faster R-CNN and pathologists, as evidenced by rradiologist-Faster R-CNN of 0.912, rPathologist-radiologist of 0.134, and rPathologist-Faster R-CNN of 0.448 respectively. The value of kappa coefficient in N staging between Faster R-CNN and pathologists was 0.573, and this value between radiologists and pathologists was 0.473. The 3 groups of Faster R-CNN, radiologists and pathologists showed no significant differences in the recurrence-free survival time for stage N0 and N1 patients, but significant differences were found for stage N2 patients. CONCLUSION: Faster R-CNN surpasses radiologists in the evaluation of pelvic metastatic LNs of rectal cancer, but is not on par with pathologists. TRIAL REGISTRATION www.chictr.org.cn (No. ChiCTR-DDD-17013842).
Adult ; Aged ; Aged, 80 and over ; Artificial Intelligence ; Female ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neural Networks (Computer) ; Pathologists ; Radiologists ; Rectal Neoplasms ; diagnostic imaging ; mortality ; pathology

AIM To prepare nanostructured lipid carriers for volatile oils from Artemisiae argyi Folium.METHODS Heated melting-ultrasonic dispersion method was applied to preparing lipid carriers.Taking solid/liquid lipid ratio,amounts of lipid,emulsifier and volatile oils as influencing factors,and average paticle size as an evaluation index,the formulation was optimized by orthogonal test.With cineole,camphor and borneol as indices,GC-MS was adopted in the content determination of volatile oils.RESULTS The optimal formulation was determined to be 5 ∶ 5 for solid/liquid lipid ratio,1％,3％ and 0.5％ for amounts of lipid,emulsifier and volatile oils,respectively.The obtained clear and transparent lipid carriers demonstrated the average particle size of (72.33 ±1.93) nm,PDI of 0.273 ± 0.004 5,and Zeta potential of (-30.59 ± 1.42) mV,whose in vitro release rate was lower than that of raw medicine within 120 h,along with a higher stability under 4 ℃ than that under 25 ℃.The entrapment efficiencies of cineole,camphor and borneol were 87.49％,86.45％ and 92.12％ with the drug loadings of 8.25％,2.00％ and 3.38％,respectively.CONCLUSION It is suggested that nanostructured lipid carriers for volatile oils from Artemisiae argyi Folium should be stored under 4 ℃ with the features of sustainedrelease and stable physicochemical properties.

BACKGROUNDCongenital heart disease (CHD) is the most common congenital malformations with high mortality and morbidity. The prevalence of CHD reported previously ranged from 4 per 1000 live births to 50 per 1000 live births. In this cross-sectional study, we aimed to document the prevalence of CHD in Langfang district of Hebei Province, China by analyzing data collected by hospitals located in 11 the counties of the district, as supported by a public health campaign.

METHODSA total of 67,718 consecutive 3-month-old infants were included from July 19, 2012 to July 18, 2014. Structural abnormalities were diagnosed based on echocardiography findings, including two-dimensional and color Doppler echocardiography results.

RESULTSOf the 67,718 infants, 1554 were found to have cardiac structural abnormalities. The total prevalence of CHD was 22.9 per 1000 live births, a value significantly higher than the previously reported prevalence of 8 cases per 1000 live births. The top five most common cardiac abnormalities were as follows: atrial septal defect (ASD, 605 cases, 8.93‰); ventricular septal defect (550 cases, 8.12‰); patent ductus arteriosus (228 cases, 3.37‰); pulmonary stenosis (66 cases, 0.97‰); and tetralogy of Fallot (32 cases, 0.47‰). The CHD prevalence differed by gender in this study ( χ2 = 23.498,P < 0.001), and the majority of ASD cases were females. Regional differences in prevalence were also found ( χ2 = 24.602,P < 0.001); a higher prevalence was found in urban areas (32.2 cases per 1000 live births) than in rural areas (21.1 cases per 1000 live births). There was a significant difference in the prevalence of CHD in preterm versus full-term infants ( χ2 = 133.443,P < 0.001). Prevalence of CHD in infants of maternal aged 35 years or over was significantly higher ( χ2 = 86.917,P < 0.001).

CONCLUSIONSThe prevalence of CHD in Langfang district was within the range reported using echocardiography. Echocardiography can be used to early diagnose the CHD.

China ; Cross-Sectional Studies ; Ductus Arteriosus ; pathology ; Echocardiography ; Female ; Heart Defects, Congenital ; pathology ; Heart Septal Defects, Atrial ; pathology ; Humans ; Male ; Prevalence ; Pulmonary Valve Stenosis ; pathology ; Tetralogy of Fallot ; pathology