Objective:To explore the adverse effects of maternal exposure to angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy on the fetus/neonate.Methods:Relevant databases at home and abroad were searched (up to April 2024), and case reports of ARB exposure during the second and third trimesters of pregnancy were collected. Data such as patient age, ARB drugs exposed to and the gestational age, concomitant drugs, maternal amniotic fluid examination, and fetal/neonatal outcomes were extracted from the literature. Descriptive statistical analysis was conducted on the information of ARB exposure during pregnancy.Results:A total of 37 case reports were included, describing the outcomes of 55 fetuses/neonates (including a pair of twins) exposed to ARBs in utero during the second and third trimesters of pregnancy of 54 pregnant women. Six kinds of ARBs were involved in the 54 pregnant women, including valsartan (31.5%, in 17 women), candesartan (25.9%, in 14 women), losartan (22.2%, in 12 women), olmesartan (11.1%, in 6 women), telmisartan (5.6%, in 3 women), and irbesartan (3.7%, in 2 women); 49 women (90.7%) took above ARBs continuously form pre-pregnancy or the first trimester of pregnancy to the second and third trimesters of pregnancy, which were mostly prescribed by non-obstetricians (internal medicine or general practice). In the 54 pregnant women, 46 had amniotic fluid examination during pregnancy, of which 45 (97.8%) had oligohydramnios or absence of amniotic fluid; 4 voluntarily induced labor to terminate pregnancy, and 50 reported the natural outcome of pregnancy and had 51 fetuses/newborns, 15 (29.4%) of which died in utero or within 1 week after birth, and 36 (70.6%) of which were discharged alive. Among the newborns, 81.3% (39/48) were premature infants, and 74.4% (32/43) were low birth weight infants. In the 55 fetuses/newborns, 48 (87.3%) had varying degrees of disease and developmental defects. The most commonly involved organ or system was kidney [72.7% (40/55)], and the major pathological change was renal tubular dysplasia; the following injury was lung/respiratory diseases and dysplasia with an incidence of [41.8% (23/55)], which was the main cause of fetal/neonatal death. Subsequently, abnormal development of skull/brain and limbs/hands and feet, abnormal circulatory system, abnormal coagulation, retinopathy, etc. have also been reported.Conclusion:ARBs exposure during the second and third trimesters of pregnancy poses significant risks to the fetus/neonate, often leading to developmental defects of renal tubular, lung, skull/brain, and limbs, and even death.

Objective:To explore the adverse effects of maternal exposure to angiotensin receptor blockers (ARBs) during the second and third trimesters of pregnancy on the fetus/neonate.Methods:Relevant databases at home and abroad were searched (up to April 2024), and case reports of ARB exposure during the second and third trimesters of pregnancy were collected. Data such as patient age, ARB drugs exposed to and the gestational age, concomitant drugs, maternal amniotic fluid examination, and fetal/neonatal outcomes were extracted from the literature. Descriptive statistical analysis was conducted on the information of ARB exposure during pregnancy.Results:A total of 37 case reports were included, describing the outcomes of 55 fetuses/neonates (including a pair of twins) exposed to ARBs in utero during the second and third trimesters of pregnancy of 54 pregnant women. Six kinds of ARBs were involved in the 54 pregnant women, including valsartan (31.5%, in 17 women), candesartan (25.9%, in 14 women), losartan (22.2%, in 12 women), olmesartan (11.1%, in 6 women), telmisartan (5.6%, in 3 women), and irbesartan (3.7%, in 2 women); 49 women (90.7%) took above ARBs continuously form pre-pregnancy or the first trimester of pregnancy to the second and third trimesters of pregnancy, which were mostly prescribed by non-obstetricians (internal medicine or general practice). In the 54 pregnant women, 46 had amniotic fluid examination during pregnancy, of which 45 (97.8%) had oligohydramnios or absence of amniotic fluid; 4 voluntarily induced labor to terminate pregnancy, and 50 reported the natural outcome of pregnancy and had 51 fetuses/newborns, 15 (29.4%) of which died in utero or within 1 week after birth, and 36 (70.6%) of which were discharged alive. Among the newborns, 81.3% (39/48) were premature infants, and 74.4% (32/43) were low birth weight infants. In the 55 fetuses/newborns, 48 (87.3%) had varying degrees of disease and developmental defects. The most commonly involved organ or system was kidney [72.7% (40/55)], and the major pathological change was renal tubular dysplasia; the following injury was lung/respiratory diseases and dysplasia with an incidence of [41.8% (23/55)], which was the main cause of fetal/neonatal death. Subsequently, abnormal development of skull/brain and limbs/hands and feet, abnormal circulatory system, abnormal coagulation, retinopathy, etc. have also been reported.Conclusion:ARBs exposure during the second and third trimesters of pregnancy poses significant risks to the fetus/neonate, often leading to developmental defects of renal tubular, lung, skull/brain, and limbs, and even death.

Objective:To investigate the current status of endoscopic treatment for gastroesophageal varices in portal hypertension in China, and to provide supporting data and reference for the development of endoscopic treatment.Methods:In this study, initiated by the Liver Health Consortium in China (CHESS), a questionnaire was designed and distributed online to investigate the basic condition of endoscopic treatment for gastroesophageal varices in portal hypertension in 2022 in China. Questions included annual number and indication of endoscopic procedures, adherence to guideline for preventing esophagogastric variceal bleeding (EGVB), management and timing of emergent EGVB, management of gastric and isolated varices, and improvement of endoscopic treatment. Proportions of hospitals concerning therapeutic choices to all participant hospitals were calculated. Guideline adherence between secondary and tertiary hospitals were compared by using Chi-square test.Results:A total of 836 hospitals from 31 provinces (anotomous regions and municipalities) participated in the survey. According to the survey, the control of acute EGVB (49.3%, 412/836) and the prevention of recurrent bleeding (38.3%, 320/836) were major indications of endoscopic treatment. For primary [non-selective β-blocker (NSBB) or endoscopic therapies] and secondary prophylaxis (NSBB and endoscopic therapies) of EGVB, adherence to domestic guideline was 72.5% (606/836) and 39.2% (328/836), respectively. There were significant differences in the adherence between secondary and tertiary hospitals in primary prophylaxis of EGVB [71.0% (495/697) VS 79.9% (111/139), χ2=4.11, P=0.033] and secondary prophylaxis of EGVB [41.6% (290/697) VS 27.3% (38/139), χ2=9.31, P=0.002]. A total of 78.2% (654/836) hospitals preferred endoscopic therapies treating acute EGVB, and endoscopic therapy was more likely to be the first choice for treating acute EGVB in tertiary hospitals (82.6%, 576/697) than secondary hospitals [56.1% (78/139), χ2=46.33, P<0.001]. The optimal timing was usually within 12 hours (48.5%, 317/654) and 12-24 hours (36.9%, 241/654) after the bleeding. Regarding the management of gastroesophageal varices type 2 and isolated gastric varices type 1, most hospitals used cyanoacrylate injection in combination with sclerotherapy [48.2% (403/836) and 29.9% (250/836), respectively], but substantial proportions of hospitals preferred clip-assisted therapies [12.4% (104/836) and 26.4% (221/836), respectively]. Improving the skills of endoscopic doctors (84.2%, 704/836), and enhancing the precision of pre-procedure evaluation and quality of multidisciplinary team (78.9%, 660/836) were considered urgent needs in the development of endoscopic treatment. Conclusion:A variety of endoscopic treatments for gastroesophageal varices in portal hypertension are implemented nationwide. Participant hospitals are active to perform emergent endoscopy for acute EGVB, but are inadequate in following recommendations regarding primary and secondary prophylaxis of EGVB. Moreover, the selection of endoscopic procedures for gastric varices differs greatly among hospitals.

A preterm male infant suffered from continuous anuria for 20 hours, with systemic edema, serum creatinine 238 μmol/L, creatinine clearance rate 19.45 ml/min, cystatin C 5.05 mg/L, serum albumin 28.8 g/L, β 2 microglobulin 6.52 mg/L, and urinary microalbumin 120.2 mg/L. He was diagnosed with acute kidney failure and hypoalbuminemia. Before his birth, his mother had been treated with sacubitril valsartan sodium tablets (50 mg, twice daily), bumetanide tablets (1 mg, once daily), clopidogrel hydrogen sulfate tablets (75 mg, once daily) and pitavastatin calcium tablets (2 mg, once daily) for 9 days due to misdiagnose. The acute kidney failure and hypoalbuminemia was considered to be associated with in utero exposure to sacubitril valsartan in the third trimester, and symptomatic and supportive treatments such as intravenous albumin supplementation, furosemide, and dopamine were given. After 56 hours of birth, his urine volume obviously increased; after 5 days, his urine volume returned to normal; after 8 days, his renal function basically returned to normal.

A preterm male infant suffered from continuous anuria for 20 hours, with systemic edema, serum creatinine 238 μmol/L, creatinine clearance rate 19.45 ml/min, cystatin C 5.05 mg/L, serum albumin 28.8 g/L, β 2 microglobulin 6.52 mg/L, and urinary microalbumin 120.2 mg/L. He was diagnosed with acute kidney failure and hypoalbuminemia. Before his birth, his mother had been treated with sacubitril valsartan sodium tablets (50 mg, twice daily), bumetanide tablets (1 mg, once daily), clopidogrel hydrogen sulfate tablets (75 mg, once daily) and pitavastatin calcium tablets (2 mg, once daily) for 9 days due to misdiagnose. The acute kidney failure and hypoalbuminemia was considered to be associated with in utero exposure to sacubitril valsartan in the third trimester, and symptomatic and supportive treatments such as intravenous albumin supplementation, furosemide, and dopamine were given. After 56 hours of birth, his urine volume obviously increased; after 5 days, his urine volume returned to normal; after 8 days, his renal function basically returned to normal.

ABSTRACT: Meningiomas are the most common primary intracranial neoplasm with diverse pathological types and complicated clinical manifestations. The fifth edition of the WHO Classification of Tumors of the Central Nervous System (WHO CNS5), published in 2021, introduces major changes that advance the role of molecular diagnostics in meningiomas. To follow the revision of WHO CNS5, this expert consensus statement was formed jointly by the Group of Neuro-Oncology, Society of Neurosurgery, Chinese Medical Association together with neuropathologists and evidence-based experts. The consensus provides reference points to integrate key biomarkers into stratification and clinical decision making for meningioma patients. REGISTRATION Practice guideline REgistration for transPAREncy (PREPARE), IPGRP-2022CN234.
Humans ; Meningioma/pathology* ; Consensus ; Neurosurgical Procedures ; Meningeal Neoplasms/pathology*

BACKGROUND: Restriction is a reliable means in the study of psychological stress, and restriction stress can suppress cellular immunity of T lymphocytes through hypothalamus-pituitary-adrenal axis.OBJECTIVE: To investigate the changes of Th1/Th2 balance due to restriction stress in cancer-loaded rats and the growth of cancer so as to explore the effect of psychological stress on cancer cells.DESIGN:Case control study based on experimental animal as subjects.SETTING: Teaching and Research Department of Microbiology and Immunology of Beijing University of Traditional Chinese Medical.MATERIALS: This study was carried out in the Immunology Laboratory of Beijing Traditional Chinese Medical University. Kunming rats of 6-8weeks old were selected. They were raised for 3 days before experiment to adapt to the environment and numbered according to their weight. Rats with the highest and lowest body weight were excluded, and the rest were randomly divided into 4 groups of 16 rats (8 male rats and 8 female rats)weighing 18 to 20 g.METHODS: S180 cancer cells were collected at 7 days of celiac subculture and rinsed with normal saline before made into cell suspensions of 1×1010 L-1 with RPMI 1640 medium. Rats were given subcutaneous injection of 0.2 mL cell suspension at the right axilla in cancer group and cancer-combined restriction group. Meanwhile, the same dosage of normal saline was used instead in normal control group and pure restriction group in the same way. After injection, movements of rats in pure restriction group and cancer-combined restriction group were restricted in specially-made tubes for 8 hours a day. Ten days later rats were killed to remove the tumor and thymus which were then weighed for calculating the thymus index. MTT colorimetry and mitogen-activated immunoblast method were used to examine the proliferation of spleen T lymphocytes and the production of Thl-type cytokines, such as interleukin-2(IL-2), interferon-γ (IFN-γ); meanwhile,ELISA technique was used to detect the level of serum Th2-type cytokines,such as interleukin-4(IL-4) and interleukin-10(IL-10).MAIN OUTCOME MEASURES: Primary outcomes: effect of restriction stress on T lymphocyte' production of IL-2 and interferon-γ, and on IL-4and IL-10 as well as the effect in promoting the cancer growth in cancer-loaded rats. Secondary outcomes: effect of restriction stress on T-lymphocyte proliferation and thymus index.RESULTS: Restriction stress significantly increased the cancer weight and decreased thymus index and the proliferation of spleen T lymphocytes. Meanwhile, IL-2 and IFN-γ produced by spleen cells also decreased, with serum IL-4 and IL-10 level obviously increased in cancer-loaded rats.CONCLUSION:The cellular immunity of cancer-loaded rats was obviously suppressed due to restriction stress, which was presented by decreased Thl-type cytokine production and increased Th2-type cytokine production,resulting in Thl/Th2 cytokine imbalance towards Th2. It may be the important mechanism of its promoting effect on the growth of cancer.

AIM To determine the antagonistic activities of new endothelin receptor antagonist CPU0214 on the left ventricle membranes and the aorta ring contraction in normal rat and its reduction effect on the mean arterial pressure in conscious DOCA salt hypertensive rats. METHODS Left ventricle membranes of normal rat hearts achieved for competition binding assay was used to investigate the antagonistic effects of CPU0214. Aorta ring contraction induced by ET 1 in normal rat was used to investigate the antagonistic activity of CPU0214. DOCA salt hypertensive rats were induced by injection of deoxycorticosterone acetate (DOCA, sc) following with 1% NaCl as drinking for 4 wk. A multiple physiological recorder was used to record the mean arterial pressure of femoral artery. The endothelin receptor change in the left ventricle membranes of DOCA salt hypertensive rat was measured by binding assays. Intraperitoneal injection of CPU0214 was used to investigate its effect on reduction of mean arterial pressure. RESULTS In the left ventricle the IC 50 of endothelin receptor antagonist CPU0214 is 16 nmol?L -1 and CPU0214 (10 ?mol?L -1 ) inhibited the ET 1 induced isolated aorta rings contraction in normal rats. Mean arterial pressure as well as B max and K d of left ventricle were increased significantly in DOCA salt hypertensive rat. CPU0214 (60 mg?kg -1 ip) significantly reduced the mean arterial pressure of conscious DOCA salt hypertensive rats especially during 60～90 min after administration. CONCLUSIONS CPU0214 has significantly antagonistic effects on the left ventricle membrane and the isolated aorta ring contraction in normal rat, which is verified by CPU0214 as a strong endothelin receptor antagonist. Furthermore its effect on the mean blood pressure reduction in conscious DOCA salt hypertensive rats, which is manifested as an abnormal endothelin system, shows its prosperity of drug development value as a new endothelin receptor antagonist.