Aim To investigate the involvement of mesencephalic astrocyte-derived neurotrophic factor(MANF)in rifampicin(RFP)-induced cholestatic liv-er injury.Methods We investigated the impact of MANF gene deletion on rifampicin-induced BAT ex-pression in mice by the MANF gene knockout mouse model.We investigated the influence of MANF knock-down on nuclear factor erythroid 2-related factor 2(Nrf2)in HepG2 cells by the MANF knockdown cell model.Results Compared with the wild-type(WT)mice,the mRNA and protein expression levels of bile salt export pump(BSEP)and multidrug-resistant asso-ciated protein4(MRP4)significantly increased in WT mice treated with RFP.However,compared to the WT mice treated with RFP,the mRNA and protein expres-sion levels of BSEP,Multidrug resistance protein 1(MDR1),multidrug resistance associated proteins 2/3/4(MRP2/3/4),and organic solute transport pro-teins α(OST α)were significantly reduced.In cell experiments we found that MANF knockdown weakened the expression of Nrf2 and its nuclear translocation by RFP.Conclusion MANF may regulate adaptive BAT expression by modulating Nrf2 expression,thereby pla-ying a protective role in RFP-induced liver injury.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Humans ; Adolescent ; Fractures, Avulsion ; Fractures, Bone ; Fracture Fixation, Internal ; Ischium/surgery*

Elemene, derived from Curcuma wenyujin, one of the "8 famous genuine medicinal materials of Zhejiang province," exhibits remarkable antitumor activity. It has gained wide recognition in clinical practice for effectiveness on tumors. Dr. XIE Tian, introduced the innovative concept of "molecular compatibility theory" by combining Chinese medicine principles, specifically the "monarch, minister, assistant, and envoy" theory, with modern biomedical technology. This groundbreaking approach, along with a systematic analysis of Chinese medicine and modern biomedical knowledge, led to the development of elemene nanoliposome formulations. These novel formulations offer numerous advantages, including low toxicity, well-defined composition, synergistic effects on multiple targets, and excellent biocompatibility. Following the principles of the "molecular compatibility theory", further exploration of cancer treatment strategies and methods based on elemene was undertaken. This comprehensive review consolidates the current understanding of elemene's potential antitumor mechanisms, recent clinical investigations, advancements in drug delivery systems, and structural modifications. The ultimate goal of this review is to establish a solid theoretical foundation for researchers, empowering them to develop more effective antitumor drugs based on the principles of "molecular compatibility theory".
Humans ; Retrospective Studies ; Antineoplastic Agents/therapeutic use* ; Neoplasms/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Sesquiterpenes/therapeutic use*

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To analyze factors affecting outcomes of single-dose methotrexate(MTX)treatment in patients with ectopic pregnancy.Methods The data of 416 patients with ectopic pregnancy treated by single-dose MTX injection in Obstetrics and Gynecology Hospital,Fudan University from Jan 2019 to Dec 2022 were retrospectively analyzed.MTX was administered on day 1,and the serum β-human chorionic gonadotrophin(β-hCG)levels were measured on posttreatment day 4 and day 7.If serum β-hCG level decreased less than 15%,it was considered as treatment failure,thus the patient was included in the failure group.If serum β-hCG level decreased more than 15%,it was considered as effective initial treatment and β-hCG levels were measured weekly until back to nonpregnant level,thus the patient was included in the success group.Clinical data and treatment outcomes were collected and outcomes-related risk factors were analyzed.Results There were 70 patients in failure group and 346 patients in success group.The proportion of patients with increased β-humanchorionic gonadotrophin(β-hCG)level before MTX treatment in failure group was significantly higher than that of patients in success group(55.2%vs.35.8%,P=0.007)and the proportion of patients with decreased β-hCG level before MTX treatment in failure group was significantly lower than that of patients in success group(43.1%vs.63.6%,P=0.007).Monocyte counts in failure group was significantly lower than that in success group[(0.43±0.13)×109/L vs.(0.47±0.17)×109/L,t=-2.001,P=0.047)].The differences of basal β-hCG level,change speed of β-hCG level,serum albumin,serum creatinine,white blood cell,neutrocyte,mean platelet volume,neutrocyte-lymphocyte ratio,platelet-lymphocyte ratio and lymphocyte-monocyte ratio between the two groups were not significant.Logistic regression analysis suggested the changing patterns of serum β-hCG level and monocyte counts were associated with treatment outcomes.Decreased β-hCG level(OR=2.313,95%CI:1.222-4.379,P=0.010)and monocyte counts≥0.6×109/L(OR=4.018,95%CI:1.207-13.378,P=0.023)were positively correlated with treatment success.Conclusion Decreased β-hCG level MTX treatment and monocyte counts≥0.6×109/L were two independent risk factors for the successful treatment of ectopic pregnancy.

Nasopharyngeal carcinoma (NPC) is the third most common malignancy with a high recurrence and metastasis rate in South China. Natural compounds extracted from traditional Chinese herbal medicines have been developed and utilized for the treatment of a variety of cancers with modest properties and slight side effects. Maackiain (MA) is a type of flavonoid that was first isolated from leguminous plants, and it has been reported to relieve various nervous system disorders and exert anti-allergic as well as anti-inflammatory effects. In this study, we demonstrated that MA inhibited proliferation, arrested cell cycle and induced apoptosis in nasopharyngeal carcinoma CNE1 and CNE2 cells in vitro and in vivo. The expression of the related proteins associated with these processes were consistent with the above effects. Moreover, transcriptome sequencing and subsequent Western blot experiments revealed that inhibition of the MAPK/Ras pathway may be responsible to the anti-tumor effect of MA on NPC cells. Therefore, the effects of MA and an activator of this pathway, tertiary butylhydroquinone (TBHQ), alone or combination, were investigated. The results showed TBHQ neutralized the inhibitory effects of MA. These data suggest that MA exerts its anti-tumor effect by inhibiting the MAPK/Ras signaling pathway and it has the potential to become a treatment for patients with NPC.
Humans ; Nasopharyngeal Carcinoma/pathology* ; Cell Line, Tumor ; Cell Proliferation ; Apoptosis ; Signal Transduction ; Nasopharyngeal Neoplasms/pathology*

Objective:To explore the neural mechanism of language dysfunction in patients with subacute stroke using functional near-infrared spectroscopy (fNIRS).Methods:Sixteen patients with non-fluent aphasia after subacute stroke (aphasia group), 16 patients with non-aphasia after stroke (non-aphasia group), and 16 healthy middle-aged and elderly subjects (control group) were enrolled into our study. The 6-min resting-state data of fNIRS were collected. Four language-related regions, Broca area, Wernicke area, dorso lateral prefrontal cortex (DLPFC), and supplementary motor area (SMA), were selected as regions of interest (ROIs), and the whole brain functional connection strength and functional connection strength in ROIs and between each two ROIs were analyzed by NirSpark software.Results:Compared with the control group (0.53±0.15) and non-aphasia group (0.47±0.12), the aphasia group had significantly decreased whole brain functional connection strength (0.29±0.14, P<0.05). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the left Wernicke area, right Wernicke area, left Broca area, left SMA area, right SMA area and left DLPFC area ( P<0.05, FDR). Compared with the control group and non-aphasia group, the aphasia group had significantly decreased functional connection strength in the right Wernicke-left Wernicke area, right Wernicke-right Broca area, right Wernicke-left Broca area, right Wernicke-right DLPFC area, right Wernicke-left DLPFC area, right Wernicke-right SMA area, right Wernicke-left SMA area, left Wernicke-right Broca area, left Wernicke-left Broca area, left Wernicke-right DLPFC area, left Wernicke-left DLPFC, left Wernicke-right SMA area, left Wernicke-left SMA area, right Broca-left Broca area, right Broca-left DLPFC area, right Broca-right SMA area, right Broca-left SMA area, left Broca-right DLPFC area, left Broca-left DLPFC area, left Broca-right SMA area, left Broca-left SMA area, right DLPFC-left DLPFC area, right DLPFC-right SMA area, right DLPFC-left SMA area, left DLPFC-right SMA area, left DLPFC-left SMA area, and right SMA-left SMA area ( P<0.05, FDR). Conclusion:Abnormal functional connectivity strength of the whole brain and language-related key brain areas might be the neural mechanism of language dysfunction in patients with non-fluent aphasia after subacute stroke.

Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Male ; Mice ; Animals ; Keratin-18 ; Actins ; Desmin ; Liver ; Hepatocytes ; Hepatic Stellate Cells

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis