OBJECTIVE: High-altitude hypoxia exposure often damages hippocampus-dependent learning and memory. Nogo-A is an important axonal growth inhibitory factor. However, its function in high-altitude hypoxia and its mechanism of action remain unclear. METHODS: In an in vivo study, a low-pressure oxygen chamber was used to simulate high-altitude hypoxia, and genetic or pharmacological intervention was used to block the Nogo-A/NgR1 signaling pathway. Contextual fear conditioning and Morris water maze behavioral tests were used to assess learning and memory in rats, and synaptic damage in the hippocampus and changes in oxidative stress levels were observed. In vitro, SH-SY5Y cells were used to assess oxidative stress and mitochondrial function with or without Nogo-A knockdown in Oxygen Glucose-Deprivation/Reperfusion (OGD/R) models. RESULTS: Exposure to acute high-altitude hypoxia for 3 or 7 days impaired learning and memory in rats, triggered oxidative stress in the hippocampal tissue, and reduced the dendritic spine density of hippocampal neurons. Blocking the Nogo-A/NgR1 pathway ameliorated oxidative stress, synaptic damage, and the learning and memory impairment induced by high-altitude exposure. CONCLUSION: Our results demonstrate the detrimental role of Nogo-A protein in mediating learning and memory impairment under high-altitude hypoxia and suggest the potential of the Nogo-A/NgR1 signaling pathway as a crucial therapeutic target for alleviating learning and memory dysfunction induced by high-altitude exposure. GRAPHICAL ABSTRACT available in www.besjournal.com.
Animals ; Oxidative Stress ; Hippocampus/metabolism* ; Rats ; Nogo Proteins/genetics* ; Male ; Rats, Sprague-Dawley ; Hypoxia/metabolism* ; Altitude ; Synapses ; Humans ; Altitude Sickness/metabolism*

Objective To investigate the factors influencing prognosis in patients with acute myocardial infarction complicated with cardiogenic shock undergoing primary percutaneous coronary intervention(PPCI).Methods Patients with acute myocardial infarction complicated with cardiogenic shock who underwent PPCI at our hospital between January 2015 and December 2019 were enrolled.Clinical baseline characteristics,coronary angiography and PCI-related parameters,and mechanical support information were collected.The patients were followed up for one year and divided into survival and death groups based on their survival status within one year.Differences in various factors between the two groups were compared.Results A total of 40 patients were enrolled,including 26 in the survival group and 14 in the death group.There were no differences in baseline data,diagnosis,risk factors,and comorbidities between the two groups.The survival group had a lower heart rate and higher blood pressure trend at admission compared to the death group.Myocardial enzymes were significantly lower in the survival group compared to the death group(median CK peak:496.00(198.25,2 830.00)U/L vs.3 040.00(405.75,5 626.53)U/L,P=0.003;median CK-MB peak:52.65(31.75,219.50)U/L vs.306.00(27.25,489.63)U/L,P=0.006).When comparing coronary angiography and PCI-related indicators between the two groups,the survival group had a higher rate of complete revascularization compared to the control group(53.85％vs.21.43％,P=0.048).The survival group had a higher proportion of extracorporeal membrane oxygenation(ECMO)combined with intra-aortic balloon pump(IABP)support compared to the control group[38.46％vs.7.14％,P=0.034].Conclusions Survival in patients with acute myocardial infarction complicated with cardiogenic shock undergoing PPCI is associated with lower level of myocardial enzymes,ECMO combined with IABP support and complete revascularization.

Objective To evaluate the effects of various polysorbates(PS)on the stability of different types of monoclonal antibody(mAb)drugs.Methods Three types of monoclonal antibodies mAbA(IgG1 proantibody drug),mAbB(IgG1 mAb)and mAbC(IgG1 mAb with Fc N297A mutation)were used as model proteins,and different kinds or contents of PS were added into the mAb formulations respectively to investigate the influencing factors.The effects of PS on the stability of mAb drugs were evaluated comprehensively by detecting the changes of quality attributes,such as protein aggregates and insoluble particles.Results PS20 and PS80 showed no significant difference in inhibiting the formation of aggregates and charge variants in the three mAbs(P>0.05),while the addition of PS80 in mAbB and PS20 in mAbC significantly inhibited the increase of insoluble particles respectively(P<0.05);The content of PS20 showed a significant effect on the detection indexes of charge variants and insoluble particles in mAbC(P<0.05).Conclusion Different types of mAbs have different sensitivities to various kinds and contents of PS.Therefore,when designing the formulation of mAbs,it is necessary to select appropriate kinds and contents of PS to further improve the stability of mAb drugs.

OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

BACKGROUND: It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time. The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse (POP) over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011. METHODS: A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1, 2004 and September 30, 2018 were included from 22 tertiary academic medical centers. The data were reported voluntarily and obtained from a database. We compared the proportion of each procedure in the 7 years before and 7 years after September 30, 2011. The data were analyzed by performing Z test (one-sided). RESULTS: The number of different procedures during October 1, 2011-September 30, 2018 was more than twice that during October 1, 2004-September 30, 2011. Regarding pelvic floor surgeries related to POP, the rate of synthetic mesh procedures increased from 38.1% (5298/13,906) during October 1, 2004-September 30, 2011 to 46.0% (14,107/30,688) during October 1, 2011-September 30, 2018, whereas the rate of non-mesh procedures decreased from 61.9% (8608/13,906) to 54.0% (16,581/30,688) (Z = 15.53, P < 0.001). Regarding synthetic mesh surgeries related to POP, the rates of transvaginal placement of surgical mesh (TVM) procedures decreased from 94.1% (4983/5298) to 82.2% (11,603/14,107) (Z = 20.79, P < 0.001), but the rate of laparoscopic sacrocolpopexy (LSC) procedures increased from 5.9% (315/5298) to 17.8% (2504/14,107). CONCLUSIONS: The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly. The rate of TVM procedures decreased while the rate of LSC procedures increased significantly. TRIAL REGISTRATION NUMBER NCT03620565, https://register.clinicaltrials.gov.
China ; Female ; Gynecologic Surgical Procedures/adverse effects* ; Humans ; Pelvic Floor/surgery* ; Pelvic Organ Prolapse/surgery* ; Surgical Mesh/adverse effects* ; Treatment Outcome ; Vagina

Objective: To observe the clinical effect and safety of Shanhaidan Granules (SHDG) combined with tadalafil tablets (TT) in the treatment of ED. METHODS: In this open multi-center case-control clinical trial, we enrolled 247 ED patients according to the designed criteria, and treated them orally with SHDG at 10 g per time tid (n = 74), TT at 5 mg per time bid (n = 52), or SHDG + TT at the above doses (n = 121), all for 8 weeks. Before and after medication, we recorded the IIEF-6, erection hardness scores (EHS), traditional Chinese medicine syndromes (TCMS) scores, penile cavernous blood flow parameters and adverse reactions, and compared them between the 3 groups of patients. RESULTS: After 8 weeks of treatment, all the patients showed significantly increased IIEF-6, EHS and TCMS scores in comparison with the baseline (P < 0.05). The total effectiveness rates in the SHDG, TT and SHDG + TT groups were 60.8%, 67.3% and 69.4% respectively based on the IIEF-6 scores, remarkably higher in the TT and SHDG + TT groups than in the SHDG group (P < 0.05), and 40.5%, 32.7% and 63.6% respectively according to the TCMS scores, markedly higher in the SHDG and SHDG + TT groups than in the TT group (P < 0.05). Single-center data manifested significantly increased peak systolic velocity (PSV) of the penile artery in the SHDG + TT and TT groups (P < 0.05). The improvement values of relevant parameters were remarkably higher in the SHDG + TT group than in the TT and SHDG groups, so were IIEF-6 scores in the TT than in the SHDG group, and TCM syndromes in the SHDG than in the TT group. No medication-related adverse events were found in any of patients after treatment, except for some mild side effects including muscle soreness and gastrointestinal reactions in a few cases, all soon relieved, none with abnormalities in blood and urine routine tests or hepatic and renal function indicators. CONCLUSIONS Shanhaidan Granules combined with tadalafil can significantly improve the erectile function and reduce TCM syndromes in ED patients, and therefore can be applied effectively and safely in clinical practice./.
Erectile Dysfunction/drug therapy* ; Humans ; Male ; Medicine, Chinese Traditional ; Penile Erection ; Syndrome ; Tadalafil/therapeutic use*

Background:The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma;therefore,the use of morcellation is limited in the USA.A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy.Methods:A national multicenter study was performed in China.From 2002 to 2014,33,723 cases were retrospectively selected.We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application.A total of 62 cases were finally pathologically confirmed as malignant postoperatively.Additionally,the medical records of the 62 patients were analyzed in details.Results:The proportion of postoperative malignancy after morcellation application was 0.18％ (62/33,723) for patients who underwent laparoscopic myomectomy.Nearly 62.9％ (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery.And,23 (37.1％) patients showed rapid growth at the final preoperative ultrasound.With respect to the pathological types,38 (61.3％) patients had detectable endometrial stromal sarcoma,13 (21.0％) had detectable uterine leiomyosarcoma,only 3 (3.2％) had detectable carcinosarcoma,and 5 (8.1％) patients with leiomyoma had an undetermined malignant potential.Conclusions:The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy.Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential,and morcellation should be avoided.

Phase 1 clinical trials is a key step for new drugs from basic experiments to human verification.Developed countries have formulated the corresponding laws , regulations and policies and guiding principles.Association The British Pharmaceutical Industry ( ABPI ) released a 2012 version of guidelines for phase 1 clinical trials.It provided professional guidances for some important problems in phase 1 clinical trials ( such as risk assessment , contracts and agreements , confidentiality , subjects , in-vestigational medicinal products and so on ).This paper makes a brief in-troduction of guiding principles for phase 1 clinical trials on the 2012 ver-sion of the ABPI.

OBJECTIVETo observe the pregnancy promoting effect of L-carnitine combined with intracytoplasmic sperm injection (ICSI) in treating male infertility with oligoasthenozoospermia.

METHODSWe assigned 129 patients with oligoasthenozoospermia to receive 2 weeks of oral L-carnitine followed by ICSI (medication group, n = 42) and ICSI alone (control group, n = 87). We compared the sperm concentration and motility, the percentage of grade a + b sperm, and sperm deformity before and after L-carnitine medication, as well as the rates of fertilization, cleavage, available embryo and clinical pregnancy between the two groups.

RESULTSThe percentage of grade a + b sperm was significantly increased after L-carnitine medication as compared with the baseline ([13.5 +/- 10.7] % vs [9.6 +/- 7.2] %, P<0.05), and so was the rate of available embryo in the medication group after ICSI in comparison with that of the control group (77.50% vs 69.04%, P<0.05).

CONCLUSIONShort-term medication of L-carnitine can improve sperm quality and raise the success rate of ICSI.

Adult ; Asthenozoospermia ; therapy ; Carnitine ; administration & dosage ; therapeutic use ; Female ; Humans ; Infertility, Male ; therapy ; Male ; Oligospermia ; therapy ; Pregnancy ; Pregnancy Outcome ; Sperm Injections, Intracytoplasmic ; methods