OBJECTIVE: To study the in vitro and in vivo antitumor effects of the polysaccharide of Alocasia cucullata (PAC) and the underlying mechanism. METHODS: B16F10 and 4T1 cells were cultured with PAC of 40 µg/mL, and PAC was withdrawn after 40 days of administration. The cell viability was detected by cell counting kit-8. The expression of Bcl-2 and Caspase-3 proteins were detected by Western blot and the expressions of ERK1/2 mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). A mouse melanoma model was established to study the effect of PAC during long-time administration. Mice were divided into 3 treatment groups: control group treated with saline water, positive control group (LNT group) treated with lentinan at 100 mg/(kg·d), and PAC group treated with PAC at 120 mg/(kg·d). The pathological changes of tumor tissues were observed by hematoxylin-eosin staining. The apoptosis of tumor tissues was detected by TUNEL staining. Bcl-2 and Caspase-3 protein expressions were detected by immunohistochemistry, and the expressions of ERK1/2, JNK1 and p38 mRNA were detected by qRT-PCR. RESULTS: In vitro, no strong inhibitory effects of PAC were found in various tumor cells after 48 or 72 h of administration. Interestingly however, after 40 days of cultivation under PAC, an inhibitory effect on B16F10 cells was found. Correspondingly, the long-time administration of PAC led to downregulation of Bcl-2 protein (P<0.05), up-regulation of Caspase-3 protein (P<0.05) and ERK1 mRNA (P<0.05) in B16F10 cells. The above results were verified by in vivo experiments. In addition, viability of B16F10 cells under long-time administration culture in vitro decreased after drug withdrawal, and similar results were also observed in 4T1 cells. CONCLUSIONS Long-time administration of PAC can significantly inhibit viability and promote apoptosis of tumor cells, and had obvious antitumor effect in tumor-bearing mice.
Mice ; Animals ; Alocasia/metabolism* ; MAP Kinase Signaling System ; Caspase 3/metabolism* ; Apoptosis ; RNA, Messenger/metabolism*

Objective:To discuss the changes of serum levels of Klotho and fibroblast growth factor 23(FGF23)in the small for gestational age(SGA)infants after birth,and to clarify their relationships with growth and development.Methods:A total of 35 SGA and 53 appropriate for the gestational age(AGA)infants were selected and divided into SGA group(n=35)and AGA group(n=53),including 51 infants in premature group,among them 20 infants in preterm SGA group and 31 infants in preterm AGA group;among them 37 infants in full-term group,15 infants in full-term SGA group and 22 infants in full-term AGA group.The clinical materials of the infants in various groups were collected.The levels of Klotho and FGF23 in serum and clinical biochemical markers of the infants on the 7th and 14th days after birth were detected.The relationships between the levels of Klotho and FGF23 in serum on the 7th and 14th days postnatally and newborn growth indicators such as body weight,body length,head circumference,chest circumference,and Kopu index,as well as their correlations with calcium and phosphorus metabolism were analyzed.Results:Compared with AGA group,the body weight,body length,head circumference,chest circumference,and Kopu index of the infants in SGA group were decreased(P<0.05).On the 7th and 14th days after birth,compared with preterm group,the serum levels of Klotho and FGF23 of the infants in full-term group were significantly increased(P<0.01).Compared with the 7th day after birth,the levels of serum Klotho of the infants in preterm and full-term groups on the 14th day were significantly increased(P<0.01),and the levels of FGF23 in serum were decreased(P<0.01).Compared with AGA group,the levels of serum Klotho and FGF23 of the infants in SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).Compared with the 7th day after birth,the levels of serum Klotho of the infants in both AGA and SGA groups on the 14th days after birth were significantly increased(P<0.01),and the FGF23 levels were decreased(P<0.05 or P<0.01).Compared with preterm AGA group,the levels of Klotho and FGF23 in serum of the infants in preterm SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).Compared with full-term AGA group,the levels of Klotho and FGF23 in serum of the infants in full-term SGA group on the 7th and 14th days after birth were significantly decreased(P<0.05 or P<0.01).In SGA group,the serum levels of Klotho and FGF23 on the 7th day after birth were positively correlated with the gestational age,body weight,body length,head circumference,chest circumference,and Kopu index(P<0.05 or P<0.01);there was a positive correlation between the serum level of Klotho and the serum level of FGF23(P<0.05).In terms of calcium-phosphorus metabolism,in SGA group,the serum level of Klotho on the 7th day after birth was positively correlated with serum phosphorus level(P<0.01),and the level of serum FGF23 on the 7th day after birth was positively correlated with serum calcium and phosphorus levels(P<0.05 or P<0.01).Conclusion:Klotho and FGF23 proteins are closely associated with growth and development and phosphate metabolism of the infants.The expression levels of Klotho and FGF23 in serum of the SGA infants postnatally are lower,but the secretion of Klotho is increased with the gradul improvement of each organ,and the decrease of FGF23 may be the adaptive response.

Hepatitis E is a globally distributed infection that varies in seroprevalence between developed and developing regions.In the less developed regions of Asia and Africa,a high seropositivity rate has been reported for hepatitis E virus(HEV)antibodies.Although acute hepatitis E is often self-limited and has a favorable prognosis,some populations experience severe manifestations,which may progress to liver failure.Moreover,some immunocompromised patients are at risk of developing chronic HEV infection and cirrhosis.Proactive screening,reducing misdiagnosis,improving patient management,timely anti-viral therapy for severe and chronic cases,and vaccination of high-risk groups are important measures to reduce the morbidity of hepatitis E.This review focused on the clinical presentation,management,and prevention of hepatitis E.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To establish a method for rapid screening and quantifying the illegal addition of metolazone in tablet candy by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF/MS).Methods The component in samples was extracted with acetonitrile,then purified by Captiva EMR-Lipid purification column,detected by UPLC-Q-TOF/MS with Agilent RRHD Eclipse Plus C18 chromatographic column(100 mm×2.1 mm,1.8μm)under Targeted MS/MS mode.Results The linear regression analysis data for the calibration plots showed a good linear relationship over the concentration range of 50-1 000 ng·mL-1 for metolazone(r=0.999 0);the value of detection limit and quantification limit was found to be 1.0 μg.g1 and 2.5 μg·g-1.The average recovery rate was 98.15％(RSD=2.2％,n=18).Conclusion The method had the advantages of simple operation,qualitative and quantitative accuracy.It could be applied to daily inspection.

Abstract: Objective To investigate the nutritional status of patients with pulmonary tuberculosis and its effects on conventional anti-tuberculosis treatment, so as to provide a basis for improving the efficacy of conventional treatment of pulmonary tuberculosis. Methods The relevant data of 168 patients with pulmonary tuberculosis admitted to Suining Central Hospital from April 2020 to April 2022 were retrospectively analyzed. Nutritional status of the patients before treatment was investigated using the Mini Nutritional Assessment (MNA) score, and the influencing factors of nutritional status before treatment were analyzed. Therapeutic effects of anti-tuberculosis drugs in the non-nutritional risk group and the nutritional risk group were comparatively analyzed. Results Among the 168 patients, 64 were assessed as having good nutritional status before treatment, 59 had the risk of malnutrition and 45 were malnourished according to the MNA score. Univariate analysis and linear regression analysis showed that age, underlying diseases, and clinical symptoms were factors affecting the MNA score before treatment (t=3.173, 3.718, 2.018, P all<0.05); whereas gender and education level were not factors affecting MNA score before treatment (t=0.065, 0.059, P all>0.05). According to the MNA score before treatment, the patients were dividedinto a non-nutritional risk group (MNA score > 23.5) and a nutritional risk group (MNA score ≤23.5). The negative conversion rate of sputum bacteria, effective rate of focal absorption in the non-nutritional risk group were 92.19% (59/64)and90.63% (58/64) , respectively, which were significantly higher than corresponding 79.85% (82/104)and76.92% (80/104) in the nutritional risk group. The drug resistance rate, adverse reaction rate, and average treatment cost of the no nutritional risk group and nutritional risk group were 7.81% (5/64) and 21.15% (12/104), 15.63% (10/64) and 31.73% (33/104), (0.62±0.13) million yuan and (0.89±0.26) million yuan, respectively, with significant differences (χ2=5.228, 5.071, 7.685, 5.396, 7.728, P all<0.05). Conclusions Patients with pulmonary tuberculosis exhibit poor nutritional status before treatment. The patients’nutritional status is easily affected by age, underlying diseases, and clinical symptoms, thereby affecting the effect of anti-tuberculosis treatment. Therefore, early nutritional intervention for tuberculosis patients should be recommended in order to prevent malnutrition and enhance the effectiveness of anti-tuberculosis treatment.

As the most common congenital disease, congenital heart disease has more and more survivors, which also means that more and more patients need to transition from teenagers to adults. This article starts from the concept of transitional care for patients with congenital heart disease, and probes into the definition, current situation, timing, influencing factors and intervention measures of transitional care for patients with congenital heart disease, so as to provide good transitional care for patients with congenital heart disease.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment

INTRODUCTION: Hospital-at-home programmes are well described in the literature but not in Asia. We describe a home-based inpatient substitutive care programme in Singapore, with clinical and patient-reported outcomes. METHODS: We conducted a retrospective cohort study of patients admitted to a hospital-at-home programme from September 2020 to September 2021. Suitable patients, who otherwise required hospitalisation, were admitted to the programme. They were from inpatient wards, emergency department and community nursing teams in the western part of Singapore, where a multidisciplinary team provided hospital-level care at home. Electronic health record data were extracted from all patients admitted to the programme. Patient satisfaction surveys were conducted post-discharge. RESULTS: A total of 108 patients enrolled. Mean age was 67.9 (standard deviation 16.7) years, and 46% were male. The main diagnoses were skin and soft tissue infections (35%), urinary tract infections (29%) and fluid overload (18%). Median length of stay was 4 (interquartile range 3-7) days. Seven patients were escalated back to the hospital, of whom 2 died after escalation. One patient died at home. There was 1 case of adverse drug reaction and 1 fall at home, and no cases of hospital-acquired infections. Patient satisfaction rates were high and 94% of contactable patients would choose to participate again. CONCLUSION Hospital-at-home programmes appear to be safe and feasible alternatives to inpatient care in Singapore. Further studies are warranted to compare clinical outcomes and cost to conventional inpatient care.
Aftercare ; Aged ; Female ; Hospitalization ; Humans ; Length of Stay ; Male ; Patient Discharge ; Retrospective Studies ; Singapore

Objective:To determine the expression of matrix metalloproteinase 13 (MMP13) in patients with psoriasis, and to evaluate the effect of tazarotene and narrow-band ultraviolet B (NB-UVB) on the expression of MMP13 in mice with psoriasis-like dermatitis.Methods:Lesional skin tissues and normal skin tissues were collected from 18 patients with psoriasis vulgaris and 10 healthy controls respectively, who were enrolled from General Hospital of Tianjin Medical University between May 2019 and August 2019, and serum samples were collected from all the subjects. A total of 25 specific pathogen-free (SPF) male BALB/c mice were randomly divided into control group, imiquimod group, imiquimod+NB-UVB group, imiquimod+tazarotene group and imiquimod+tazarotene+NB-UVB group. The control group received topical vaseline cream on the back once every morning; imiquimod group and imiquimod+NB-UVB group received imiquimod cream on the back once every morning; imiquimod+tazarotene group and imiquimod+tazarotene+NB-UVB group received imiquimod cream on the back once every morning, and tazarotene cream on the back once at night; imiquimod+NB-UVB group and imiquimod+tazarotene+NB-UVB group received NB-UVB irradiation on the back every other day at noon, with the dose being 300 mJ/cm 2 in the first session and increasing by 50 mJ/cm 2 in every session. The modeling lasted 7 days. After successful modeling, blood samples were obtained from the eyeballs of the mice, and skin tissues were resected from the back of the mice after being sacrificed by cervical dislocation on day 8. Changes in the epidermal thickness and pathological manifestations were observed by hematoxylin and eosin (HE) staining, protein expression of MMP13 in skin tissues was determined by immunohistochemical study, and the serum level of MMP13 was detected by enzyme-linked immunosorbent assay. Comparisons between 2 groups were performed by using two-independent-sample t test, comparisons among several groups by using one-way analysis of variance, multiple comparisons by using least significant difference- t test, and comparisons of enumeration data by using chi-square test. Results:The skin lesions of the patients with psoriasis were strongly positive for MMP13, and the MMP13 expression levels in the epidermis and serum (84.11±17.16, 13.29±3.95 μg/L, respectively) were significantly higher in the patients with psoriasis than in the healthy controls (11.98±4.08, 7.46±1.58 μg/L, respectively, both P< 0.01) . Compared with the control group (1.26±0.04 μm, 25.40±2.34, 185.76±7.22 μg/L, respectively) , a significant increase was observed in the epidermis thickness (7.93±0.59 μm, P< 0.01) , as well as MMP13 levels in the epidermis and serum in the imiquimod group (147.14±5.53, 215.98±15.17 μg/L, respectively, both P< 0.01) . Compared with the imiquimod group, the imiquimod+tazarotene group, imiquimod+NB-UVB group, and imiquimod+tazarotene+NB-UVB group all showed significantly decreased epidermal thickness (3.56±0.37 μm, 3.83±0.39 μm, 2.14±0.34 μm, respectively, all P< 0.05) , MMP13 levels in the epidermis (120.42±3.23, 91.08±0.46, 71.12±7.11, respectively, all P< 0.05) and serum (197.39±3.92 μg/L, 196.13±11.76 μg/L, 183.21±14.99 μg/L, respectively, all P< 0.05) . Conclusions:MMP13 protein expression markedly increased in the skin lesions and sera of patients with psoriasis, and decreased in skin lesions and sera of mice with psoriasis-like dermatitis after the treatment with tazarotene and NB-UVB. MMP13 may be involved in the development of psoriasis, and tazarotene and NB-UVB may inhibit the development of psoriasis by reducing the expression of MMP13.