Objective To observe the effect of abdominal massage combined with thumb-tack needling for subcutaeous embedding on sleep homeostasis system in rats with anxiety insomnia.Methods Forty rats were randomly divided into normal group,model group,abdominal massage group,thumb-tack needling for subcutaeous embedding group and abdominal massage plus thumb-tack needling for subcutaeous embedding group,with 8 rats in each group.Except for the normal group,the rats in the other groups were used to replicate the model of anxiety insomnia by multi-factor compound stimulation.After the corresponding intervention,Morris water maze test was used to detect the level of learning and memory.Open field test was used to detect the degree of anxiety stress.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hypothalamic ventral lateral preoptic nucleus(VLPO)neurons.Immunohistochemistry,real-time quantitative polymerase chain reaction(qRT-PCR)and Western Blot were used to detect the protein and mRNA expression of N-methyl-D-aspartate(NMDA)receptor subunits NR1,NR2B and calmodulin kinase Ⅱ(CaMK Ⅱ)in hypothalamic VLPO area,respectively.Results Compared with the normal group,the daytime anxiety symptoms of the rats in the model group were aggravated,the sleep latency was prolonged and the duration was shortened(P＜0.01).The average total swimming distance and average escape latency of the water maze directional navigation experiment were increased(P＜0.01).The number of crossing the hidden platform and the retention time of the target quadrant in the space exploration experiment were decreased(P＜0.01).The movement distance,the number of central grid crossings and the retention time of the central grid in the open field experiment were significantly reduced(P＜0.01).There was no significant difference in the modification frequency and the number of uprights(P＞0.05).Neurons in the VLPO brain region showed pathological damage.The protein and mRNA expression levels of NR1 and CaMK Ⅱ were decreased(P＜0.01)in VLPO brain region,and the protein and mRNA expression levels of NR2B were increased(P＜0.01).Compared with the model group,the level of learning and memory in the water maze test and the degree of anxiety stress in the open field test were significantly restored in the abdominal massage group,the thumb-tack needling for subcutaeous embedding group and the abdominal massage combined with thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01),the neuronal damage in the VLPO brain region was improved,the protein and mRNA expression levels of NR1,CaMK Ⅱ were increased(P＜0.05 or P＜0.01),and the protein and mRNA expression levels of NR2B were decreased(P＜0.05 or P＜0.01).The improvement effect of the above indexes in the abdominal massage plus thumb-tack needling for subcutaeous embedding group was superior to that in the abdominal massage group or thumb-tack needling for subcutaeous embedding group(P＜0.05 or P＜0.01).Conclusion Abdominal massage combined with thumb-tack needling for subcutaeous embedding can promote sleep and anti-anxiety in rats with anxiety insomnia.The related mechanism may be related to adjusting the dynamic balance between NR1/NR2B in VLPO brain area and up-regulating the expression level of CaMK Ⅱ,improving the function of neurons in VLPO brain area,and then restoring the regulation of sleep homeostasis system.

OBJECTIVE: To investigate the involvement of endothelial cells (ECs)-derived exosomes in the anti-apoptotic effect of Danhong Injection (DHI) and the mechanism of DHI-induced exosomal protection against postinfarction myocardial apoptosis. METHODS: A mouse permanent myocardial infarction (MI) model was established, followed by a 14-day daily treatment with DHI, DHI plus GW4869 (an exosomal inhibitor), or saline. Phosphate-buffered saline (PBS)-induced ECs-derived exosomes were isolated, analyzed by miRNA microarray and validated by droplet digital polymerase chain reaction (ddPCR). The exosomes induced by DHI (DHI-exo), PBS (PBS-exo), or DHI+GW4869 (GW-exo) were isolated and injected into the peri-infarct zone following MI. The protective effects of DHI and DHI-exo on MI hearts were measured by echocardiography, Masson's trichrome staining, and TUNEL apoptosis assay. The Western blotting and quantitative reverse transcription PCR (qRT-PCR) were used to evaluate the expression levels of miR-125b/p53-mediated pathway components, including miR-125b, p53, Bak, Bax, and caspase-3 activities. RESULTS: DHI significantly improved cardiac function and reduced infarct size in MI mice (P<0.01), which was abolished by the GW4869 intervention. DHI promoted the exosomal secretion in ECs (P<0.01). According to the results of exosomal miRNA microarray assay, 30 differentially expressed miRNAs in the DHI-exo were identified (28 up-regulated miRNAs and 2 down-regulated miRNAs). Among them, DHI significantly elevated miR-125b level in DHI-exo and DHI-treated ECs, a recognized apoptotic inhibitor impeding p53 signaling (P<0.05). Remarkably, treatment with DHI and DHI-exo attenuated apoptosis, elevated miR-125b expression level, inhibited capsase-3 activity, and down-regulated the expression levels of proapoptotic effectors (p53, Bak, and Bax) in post-MI hearts, whereas these effects were blocked by GW4869 (P<0.05 or P<0.01). CONCLUSION DHI and DHI-induced exosomes inhibited apoptosis, promoted the miR-125b expression level, and regulated the p53 apoptotic pathway in post-infarction myocardium.
Mice ; Animals ; Tumor Suppressor Protein p53/metabolism* ; Endothelial Cells/metabolism* ; Exosomes/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Myocardium/metabolism* ; Myocardial Infarction/drug therapy* ; Apoptosis ; MicroRNAs/metabolism*

Objective: To analyze the short-time efficacy of empagliflozin in the treatment of glycogen storage disease type Ⅰb (GSD Ⅰb). Methods: In this prospective open-label single-arm study, the data of 4 patients were collected from the pediatric department in Peking Union Medical College Hospital from December 2020 to December 2022. All of them were diagnosed by gene sequencing and had neutropenia. These patients received empagliflozin treatment. Their clinical symptoms such as height and weight increase, abdominal pain, diarrhea, oral ulcer, infection times, and drug applications were recorded at 2 weeks, 1 month, 2 months, 3 months, 6 months, 9 months, 12 months, and 15 months after treatment to assess the therapeutic effect. The liquid chromatography-tandem mass spectrometry method was used to monitor the changes in 1, 5-anhydroglucitol (1, 5AG) concentration in plasma. At the same time, adverse reactions such as hypoglycemia and urinary tract infection were closely followed up and monitored. Results: The 4 patients with GSD Ⅰb were 15, 14, 4 and 14 years old, respectively at the beginning of empagliflozin treatment, and were followed up for 15, 15, 12 and 6 months, respectively. Maintenance dose range of empagliflozin was 0.24-0.39 mg/(kg·d). The frequency of diarrhea and abdominal pain decreased in cases 2, 3, and 4 at 1, 2 and 3 months of treatment, respectively. Their height and weight increased at different degrees.The absolute count of neutrophils increased from 0.84×10⁹, 0.50×10⁹, 0.48×10⁹, 0.48×10⁹/L to 1.48×10⁹, 3.04×10⁹, 1.10×10⁹, 0.73×10⁹/L, respectively. Granulocyte colony-stimulating factor was gradually reduced in 1 patients and stopped in 3 patient. Plasma 1, 5 AG levels in 2 children were significantly decreased after administration of empagliflozin (from 46.3 mg/L to 9.6 mg/L in case 2, and from 56.1 mg/L to 15.0 mg/L in case 3). All 4 patients had no adverse reactions such as hypoglycemia, abnormal liver or kidney function, or urinary system infection. Conclusion: In short-term observation, empagliflozin can improve the symptoms of GSD Ⅰb oral ulcers, abdominal pain, diarrhea, and recurrent infection, also can alleviate neutropenia and decrease 1, 5AG concentration in plasma, with favorable safety.
Humans ; Child ; Child, Preschool ; Adolescent ; Prospective Studies ; Glycogen Storage Disease Type I/drug therapy* ; Neutropenia ; Abdominal Pain ; Diarrhea/drug therapy* ; Hypoglycemia

The present study aims to investigate the correlation between irritant toxicity variation and lectin content variation during the processing of Pinelliae Rhizoma products and to explore the feasibility of Western blot as a method for the detection of lectin. We processed Pinelliae Rhizoma Praeparatum Cum Alumine, Pinelliae Rhizoma Praeparatum, and Pinelliae Rhizoma Praeparatumcum Zingibere et Alumine to different degrees and then analyzed their irritant toxicity via Draize rabbit eye test. Western blot was employed to determine the lectin content in Pinelliae Rhizoma products processed with different methods. The correlation between toxicity variation and lectin content variation was then analyzed. Different decoction pieces of Pinelliae Rhizoma were collected for the determination of lectin content. The three processed products of Pinelliae Rhizoma showed gradually decreased toxicity and lectin content as the processing continued. The decreasing trend of lectin content was consistent with that of irritant toxicity during processing, which indicated that the change in lectin content could reflect the trend of irritant toxicity. No band of lectin appeared in the Western blot of processed products of Pinelliae Rhizoma, which suggested that western blotting can be used for the detection of toxic lectin in the processed products of Pinelliae Rhizoma. Lectin should not be detected in the Pinelliae Rhizoma products processed according to the methods in the Chinese Pharmacopoeia.
Animals ; Drugs, Chinese Herbal/toxicity* ; Irritants ; Lectins ; Pinellia ; Rabbits ; Technology, Pharmaceutical/methods*

Objective: To investigate death and attrition in HIV-infected children under initial antiretroviral therapy (ART) and associated factors in Guangxi Zhuang autonomous region. Methods: This retrospective cohort study was conducted in HIV-infected children under initial ART in Guangxi from 2004 to 2019, data from ART information system of National comprehensive AIDS prevention and treatment information system. Cox proportional hazards models were used to assess factors associated with the death and attrition. Results: In 943 HIV-infected children, the overall mortality and attrition rates were 1.00/100 person-years and 0.77/100 person-years, respectively. The mortality and attrition rates within the first year of ART were 3.90/100 person-years and 1.67/100 person-years, respectively. The cumulative survival rate during the first, second, fifth and tenth year after ART was 96.14%, 95.80%, 93.68% and 91.54%, respectively. Multivariate Cox proportional hazards models results showed that being female (aHR=2.00, 95%CI: 1.17-3.40), CD4⁺T lymphocytes (CD4) counts before ART <200 cells/μl (aHR=2.79, 95%CI: 1.54-5.06), weight-for-age Z score before ART <-2 (aHR=2.38, 95%CI: 1.32-4.26), hemoglobin before ART <80 g/L (aHR=2.47, 95%CI: 1.24-4.92), initial ART with LPV/r (aHR=5.05, 95%CI: 1.15-22.12) were significantly associated with death; being female (aHR=2.23, 95%CI: 1.22-4.07) and initial ART with LPV/r (aHR=2.02, 95%CI: 1.07-3.79) were significantly associated with attrition. Conclusions: The effect of ART in HIV-infected children in Guangxi was better, but the mortality and attrition rates were high within the first year of treatment. It is necessary to strengthen the training in medical staff and health education in HIV-infected children and their parents in order to improve the treatment effect.
Anti-HIV Agents/therapeutic use* ; Child ; China/epidemiology* ; Female ; HIV Infections/drug therapy* ; Humans ; Male ; Proportional Hazards Models ; Retrospective Studies

OBJECTIVE: To construct a preoperative evaluation system for partial nephrectomy using CT three-dimensional visualization technology and to explore its practical value. METHODS: The clinical data of the patients who underwent partial nephrectomy for renal tumors in Department of Urology, Peking University First Hospital were collected retrospectively. At the same time, the homogenized standard data of patients who underwent partial nephrectomy for renal tumors were collected in 16 clinical centers in China. The CT three-dimensional visualization system was applied (IPS system, Yorktal) to evaluate tumor anatomy, blood supply, perirenal fat and other information. The parameters were summarized to build a three-dimensional nephrometry system, on the basis of which virtual surgery design and intraoperative navigation were completed. RESULTS: A three-dimensional visualization image was established based on the enhanced CT urography. The nephrometry system included the longest diameter and volume of the tumor, proportion volume of tumor invading the parenchyma, maximum depth of the tumor invading the parenchyma, contact surface area, flatness of the tumor surface, renal segment where the tumor was located, vascular variation, and perirenal fat. The average two-dimensional diameter of the tumor was (2.78±1.43) cm, the average three-dimensional maximum diameter was (3.09±1.35) cm, and the average postoperative pathological size was (3.01±1.38) cm. The maximum tumor diameter in the three-dimensional image was significantly related to the prolonged renal artery clamping time and intra-operative blood loss (r=0.502, P=0.020; r=0.403, P=0.046). The three-dimensional and pathological tumor volume were (25.7±48.4) cm³ and (33.0±36.4) cm³, respectively (P=0.229). The tumor volume was significantly related to the intraoperative blood loss (r=0.660, P < 0.001). The proportion volume of the tumor invading into renal parenchyma was significantly related to the prolongation of renal artery clamping and the occurrence of postoperative complications (r=0.410, P=0.041; r=0.587, P=0.005). The tumor contact surface area and the presence of vascular variation did not show correlation with the perioperative data and postoperative complications. While the preoperative evaluation was completed, the reconstructed three-dimensional image could be zoomed, rotated, combined display, color adjustment, transparency, and simulated cutting on the Touch Viewer system. The process generally consisted of showing or hiding the tissue, adjusting the transparency of the interested area, rotating and zooming the image to match the position of the surgical patient. Together, these functions met the requirements of preoperative virtual surgery plan and intraoperative auxiliary navigation. CONCLUSION Three-dimensional images can provide a more intuitive anatomical structure. The CT three-dimensional visua-lization system clearly displays tumor anatomical parameters, blood supply and perirenal fat. The three-dimensional nephrometry system for renal tumors can help predict the difficulty of partial nephrectomy and perioperative complications. Importing the reconstructed three-dimensional visualization image into the specified program or robot operating system can complete virtual surgery and intraoperative navigation, helping the surgeon to better grasp the surgical process. The indexes included in the nephrometry system and the score weights of each index need to be confirmed and perfected by multi-center study with large samples.
China ; Humans ; Kidney/surgery* ; Kidney Neoplasms/surgery* ; Laparoscopy ; Nephrectomy ; Retrospective Studies

Objective: To observe the effects of acupuncture plus spinal manipulations on the physical functioning and levels of alkaline phosphatase (ALP), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and osteoprotegerin (OPG) in patients with ankylosing spondylitis (AS). Methods: A total of 128 AS cases were allocated into a control group and an observation group using random number table method, with 64 cases in each group. Patients in both groups took sulfasalazine and meloxicam. Patients in the observation group received additional acupuncture plus spinal manipulations. The efficacy, Bath AS functional index (BASFI), Bath AS disease activity index (BASDAI), and the levels of ALP, ESR, CRP and OPG were compared between the two groups after eight weeks of treatment. Results: After treatment, the symptom scores of traditional Chinese medicine in both groups were decreased (all P<0.05), and these scores in the observation group were significantly lower than in the control group (all P<0.05); the VAS, BASFI and BASDAI scores in both groups were decreased (all P<0.05), and these scores in the observation group were significantly lower than in the control group (all P<0.05); and the ALP, ESR, CRP and OPG levels in both groups were decreased (all P<0.05), and these levels in the observation group were significantly lower than in the control group (all P<0.05). The total efficacy rate was 92.2％ in the observation group, versus 78.1％ in the control group, presenting a statistical significance (P<0.05). Conclusion: Conventional medication combined with acupuncture and spinal manipulations can improve clinical symptoms, accelerate the recovery of physical functioning, and reduce the ALP, ESR, CRP and OPG levels.

BACKGROUND: Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China. METHODS: The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD. RESULTS: A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05). CONCLUSION Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.
Birth Weight ; Bronchopulmonary Dysplasia ; China/epidemiology* ; Delivery Rooms ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Extremely Premature ; Infant, Newborn ; Male ; Pregnancy

BACKGROUND: Acute heart failure (AHF) is the most common disease in emergency departments (EDs). However, clinical data exploring the outcomes of patients presenting AHF in EDs are limited, especially the long-term outcomes. The purposes of this study were to describe the long-term outcomes of patients with AHF in the EDs and further analyze their prognostic factors. METHODS: This prospective, multicenter, cohort study consecutively enrolled 3335 patients with AHF who were admitted to EDs of 14 hospitals from Beijing between January 1, 2011 and September 23, 2012. Kaplan-Meier and Cox regression analysis were adopted to evaluate 5-year outcomes and associated predictors. RESULTS: The 5-year mortality and cardiovascular death rates were 55.4% and 49.6%, respectively. The median overall survival was 34 months. Independent predictors of 5-year mortality were patient age (hazard ratio [HR]: 1.027, 95 confidence interval [CI]: 1.023-1.030), body mass index (BMI) (HR: 0.971, 95% CI: 0.958-0.983), fatigue (HR: 1.127, 95% CI: 1.009-1.258), ascites (HR: 1.190, 95% CI: 1.057-1.340), hepatic jugular reflux (HR: 1.339, 95% CI: 1.140-1.572), New York Heart Association (NYHA) class III to IV (HR: 1.511, 95% CI: 1.291-1.769), heart rate (HR: 1.003, 95% CI: 1.001-1.005), diastolic blood pressure (DBP) (HR: 0.996, 95% CI: 0.993-0.999), blood urea nitrogen (BUN) (HR: 1.014, 95% CI: 1.008-1.020), B-type natriuretic peptide (BNP)/N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in the third (HR: 1.426, 95% CI: 1.220-1.668) or fourth quartile (HR: 1.437, 95% CI: 1.223-1.690), serum sodium (HR: 0.980, 95% CI: 0.972-0.988), serum albumin (HR: 0.981, 95% CI: 0.971-0.992), ischemic heart diseases (HR: 1.195, 95% CI: 1.073-1.331), primary cardiomyopathy (HR: 1.382, 95% CI: 1.183-1.614), diabetes (HR: 1.118, 95% CI: 1.010-1.237), stroke (HR: 1.252, 95% CI: 1.121-1.397), and the use of diuretics (HR: 0.714, 95% CI: 0.626-0.814), β-blockers (HR: 0.673, 95% CI: 0.588-0.769), angiotensin-converting enzyme inhibitors (ACEIs) (HR: 0.714, 95% CI: 0.604-0.845), angiotensin-II receptor blockers (ARBs) (HR: 0.790, 95% CI: 0.646-0.965), spironolactone (HR: 0.814, 95% CI: 0.663-0.999), calcium antagonists (HR: 0.624, 95% CI: 0.531-0.733), nitrates (HR: 0.715, 95% CI: 0.631-0.811), and digoxin (HR: 0.579, 95% CI: 0.465-0.721). CONCLUSIONS The results of our study demonstrate poor 5-year outcomes of patients presenting to EDs with AHF. Age, BMI, fatigue, ascites, hepatic jugular reflux, NYHA class III to IV, heart rate, DBP, BUN, BNP/NT-proBNP level in the third or fourth quartile, serum sodium, serum albumin, ischemic heart diseases, primary cardiomyopathy, diabetes, stroke, and the use of diuretics, β-blockers, ACEIs, ARBs, spironolactone, calcium antagonists, nitrates, and digoxin were independently associated with 5-year all-cause mortality.
Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Beijing/epidemiology* ; Biomarkers ; Cohort Studies ; Emergency Service, Hospital ; Follow-Up Studies ; Heart Failure/mortality* ; Humans ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Prospective Studies

【Objective】 To explore the maximum tolerated dose(MTD) of pegylated liposome doxorubicin(PLD) when combined with cisplatin as a modified regimen for osteosarcoma. 【Methods】 A total of 14 patients with pathologically confirmed metastatic or unresectable osteosarcoma received one cycle of PLD combined with cisplatin therapy. The study used a traditional 3+3 design, with three PLD dose levels(40, 50, and 60 mg/ m², day 1). It was designed to recruit three patients initially at each dose level. Cisplatin was given at a dose of 100 mg/m²(administered within four days) for each patients. Patients received prophylactic granulocyte stimulating factor therapy 48 h after chemotherapy. Toxicities were documented according to the the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0(NCI CTCAE v4.0) . 【Results】 Of the 14 patients, 9 were male and 5 female, with a median age of 20 years(range 14~43). Both of the patients at dose level of 60 mg/m² experienced dose-limiting toxicity(DLT) (grade 3 oral mucositis and grade 4 neutropenic fever). Only 1 of the 9 patients at dose level of 50 mg/m² experienced DLT(grade 4 thrombocytopenia lasting for more than 3 days) and thus the MTD was 50 mg/m². Most common grade 3~4 adverse events across all cohorts included neutropenia(12 cases, 12/14), thrombocytopenia(7 cases, 7/14), anemia(4 cases, 4/14) and oral mucositis(2 cases, 2/14). All the adverse events were relieved after symptomatic and supportive treatment. No treatment-related death was observed. 【Conclusions】 For advanced osteosarcoma, when combined with cisplatin, the MTD of PLD was 50 mg/m². The main DLT was oral mucositis and neutropenic fever. The adverse events can be relieved after symptomatic treatment.