Objective To explore the clinical effect of intravenous immunoglobulin(IVIG)on chronic obstructive pulmonary disease(COPD)and fungal infection.Methods Seventy-two COPD patients with fungal infection were randomly and equally divided into conventional and intervention group.Patients in conventional group were treated with common schedule for COPD plus antifungal agents;patients in intervention group received 1 0 g/d IVIG besides routine therapy.Length of hospital stay and prognosis were recorded,and therapeutic effectiveness were evaluated. Results The effectiveness rate of intervention group was significantly higher than that of conventional group ([88.89%,32/36]vs [66.67%,24/36]);the average length of hospital stay was significantly shorter than conven-tional group ([12.62±7.51]d vs [20.81±6.92]d),and mortality was lower than conventional group ([5.56%, 2/36]vs [22.22%,8/36]),the differences were statistically significant (P<0.05).Conclusion IVIG for treating COPD with invasive pulmonary fungal infection can improve therapeutic efficacy,shorten length of hospital stay and decrease mortality rate.

Objective To investigate the influence and the clinical significance of interleukin-2 (IL-2) on T lymphocyte subgroup after chemotherapy in acute myeloid leukemia patients. Methods Fiftyfour acute myeloid leukemia patients were divided into treatment group (chemotherapy combined with IL-2,28 cases) and control group (pure chemotherapy,26 cases) by radom digits table. In treatment group, IL-2400 000 U was dripped after chemotherapy for 14 days. Then the T lymphocyte subgroup change before and after treatment was examined. Results After 14 days' treatment, the levels of CD3 (0.6026±0.2275 ),CD4(0.4972±0.1224),CD56(0.3016±0.1053 ) in treatment group were significantly higher than those before treatment(0.3926±0.2010,0.2264±0.1190,0.1729±0.1226) and in control group (0.4352±0.1930,0.2738±0.1362,0.1937±0.1268)(P< 0.05). Conclusion IL-2 treatment can obviously raise the levels of T lymphocyte subgroup and can raise the immunologic function.

Objective To investigate the effect of intrathecal injection of Tanshinone Ⅱ A on bone cancer pain behavior and spinal IL-1 β,IL-6,TNF-α expression.Methods According to the random number table method,84 C3H/HeNCrlVr male mice were divided into:(1) Tanshinone ⅡA 10 μg group:the tumor mice were treated by intrathecal administration (once daily on the days 14-20 after inoculation of tumor cells) with Tanshinone ⅡA 10 μg; (2)Tanshinone ⅡA 20 μg group:the tumor mice were treated with Tanshinone ⅡA 20 μg; (3)Tanshinone ⅡA 40 μg group:the tumor mice were treated with Tanshinone ⅡA 40 μg; (4) normal control group:the mice were given food and water ad libitum; (5) DMSO+Sham group:the sham mice were treated with the same volume of 5％DMSO; (6) Tanshinone ⅡA+Sham group:the sham mice were treated with Tanshinone ⅡA 40 μg; (7)DMSO+Tumor group:the tumor mice were treated with the same volume of 5％DMSO.The mice pain behaviors were assessed with the paw withdrawal thermal latency (PWTL) at the corresponding time points,then the mice were killed and the samples of spinal cord were detected by real-time PCR.Results The basic values of PWTL had no significant differences among all groups (P＞0.05).At day 14 after operation,no significant difference (P＞0.05) was found in the PWTL value between normal control group and the sham operation group.But in tumor group,the PWTL value was significantly lower than that of normal control group (P＜0.05).At day 21 after operation,the PWTL and the level of spinal IL-1 β,IL-6,TNF-α expression had no significant differences (P＞0.05) among normal control group,Tanshinone ⅡA+Sham group and DMSO+Sham group.The PWTL ((6.19± 1.26)s) in DMSO+ Tumor group was significantly lower than that of normal control group((16.01± 1.59)s) (P＜0.05),but the level of IL-1β,IL-6,TNF-α expression was higher than that of normal control group.Compared with the normal group,the PWTL ((9.83±1.26)s;(10.29±2.95) s) of Tanshinone Ⅱ A 20 μg and 40 μg group was higher,and the level of spinal IL-1β,IL-6,TNF-α expression was lower (P＜0.05).The PWTL and the levels of spinal IL-1β,IL-6,TNF-αexpression had no significant differences between Tanshinone ⅡA 10 μg group ((6.67 ± 0.96) s) and DMSO + Tumor group(P＞0.05).Conclusion Intrathecal injection of Tanshinone Ⅱ A plays a role in anti-cancer pain,and inhibition of spinal inflammatory cytokine release may be one of its mechanisms.

Purpose: Our research aimed to investigate the influence of miR-103a-3p on the growth and apoptosis of colorectal cancer (CRC) cells. Materials and Methods: Bioinformatics was employed to analyze differentially expressed microRNAs and predict target genes. qRT-PCR was applied to detect the expression of miR-103a-3p in CRC and normal cells. HCT116 and Caco-2 were chosen, and miR-103a-3p mimics, miR-103a-3p inhibitor, as well as specific siRNAs targeting GREM2, were constructed. We subsequently evaluated alternations in cell proliferation, cell cycle and cell cycle regulators, apoptosis, and related proteins (Bcl-2 and Bax) by CCK-8 testing, Western blotting, luciferase reporter, colony formation, and Annexin V-FITC/PI. Possible binding sites for miR-103a-3p on the 3'UTR of GREM2 were checked with luciferase assay, and the impact of GREM2 on miR-103a-3p activity was also validated with above biological function testing. Additionally, the effect of miR-103a-3p knockdown in CRC cells and the molecular mechanism of miR-103a-3p targeting GREM2 were also studied. Results: Bioinformatics analysis revealed that miR-103a-3p expression increased remarkably in CRC, and targeted regulatory correlation existed between miR-103a-3p and GREM2. MiR-103a-3p inhibitor significantly impeded proliferative capacity and caused cell cycle arrest, as well as apoptosis, in HCT116 and Caco-2 cells. Consistent with this finding, overexpression of GREM2 showed similar effects to miR-103a-3p inhibition. Moreover, we demonstrated that miR-103a-3p connected target GREM2 and GREM2 knockdown reversed the effects of miR-103a-3p inhibitor on HCT116 and Caco-2 cell proliferation, cell cycle, and apoptosis. Further study showed that miR-103a-3p targeting GREM2 appeared to affect CRC progression via the transforming growth factor-β pathway. Conclusion MiR-103a-3p could augment CRC progression by targeting GREM2 and that miR-103a-3p/GREM2 could be potential novel targets for CRC therapy.

Objective To investigate the current staffing of nurses and need of hospital nursing human resources in China.Methods Data were collected from 181 secondary and tertiary hospitals and 9774 nurses in mainland China by questionnaires.Results The average doctor-nurse ratio was 1 ∶ 1.39 in tertiary hospitals and 1 ∶ 1.31 in secondary hospitals.The doctor-nurse ratios in 164 hospitals (97.6％) and the proportion of nurses in health care staff in 105 hospitals (61.8％) had not reached the standard set by the Ministry of Health of China.62.3％ nurses held secondary diploma for their initial nursing education.The constituent ratio of nurses held secondary diploma decreased,while the ratio of nurses held advanced diploma and bachelor degree increased in the last 5 years from 2003 to 2007.Sixty percent of newly employed nurses were contract nurses in 2003.The proportion increased to 78％ in 2007,and in some regions it accounted for more than 90％ of new nurses.The needs and constituent ratio of nurses with.secondary diploma and advanced diploma would decrease while nurses with bachelor degree and master degree would increase in the next 5 years (from 2009 to 2013).Conclusions The nursing shortage is still severe in China,and nursing staff mainly held secondary diploma for their initial nursing education.Most of new nurses were employed as conwact nurses.The need of hospitals for nurses has increased,especially for nurses with higher educational level such as bachelor degree and master degree,while the need for secondary diploma hold ers have decreased.The need for advanced diploma holders has increased in the last 5 years and would decrease in the next 5 years,but they would still be the majority of employed nurses.The authors suggested that the staffing of nursing manpower,the work environments and career development of contract nurses should be improved,and the initial nursing education should be upgraded to meet the needs of hospitals.

Objective To investigate the value of third generation dual-source CT in early differential diagnosis of intracranial hemorrhage and iodinated contrast medium after endovascular treatment of acute ischemic stroke (AIS).Methods Totally 78 patients with AIS underwent endovascular treatment were prospectively enrolled.Dual-energy CT (DECT) examination (80 kV/Sn150 kV) of the head was performed after treatment with a third generation dual-source CT scanner.Iodine overlay maps and virtual non-contrast images were post-processed.Taking conventional brain CT images obtained 24 48 h after AIS attack as references,the accuracy,sensitivity,specificity,positive predictive value (PPV) and negative predictive value (NPV) of DECT for identifying hemorrhage were computed respectively.Results Totally 31 patients with 53 foci of intracranial hyper-attenuation were finally enrolled.Among 53 foci,26 were correctly diagnosed as hemorrhage by DECT,23 were correctly diagnosed as iodinated contrast medium,while 1 calcification was misdiagnosed as hemorrhage combined with iodinated contrast medium,3 were misdiagnosed as contrast medium which showed delayed hemorrhagic transformation.The sensitivity,specificity and accuracy of DECT was 89.66％ (26/29),95.83％ (23/24) and 92.45％ (49/53),PPV and NPV was 96.30％ (26/27) and 88.46％ (23/26),respectively.Conclusion The third generation dual-source CT is available in early and accurate diagnosis of hemorrhagic transformation after endovascular treatment of AIS,which can help clinicians to adjust the subsequent treatment strategies in time.

Objective:To study the clinical characteristics of ureaplasma urealyticum (UU) infection in preterm infants with gestational age <34 weeks.Methods:From January 2017 to December 2021, premature infants with gestational age <34 weeks admitted to neonatal department of our hospital were enrolled in this prospective cohort study. UU-DNA from respiratory tract samples were examined using quantitative fluorescence polymerase chain reaction method. The infants were assigned into UU (+) group and UU (-) group. Perinatal factors and clinical characteristics were compared between the two groups.Results:A total of 182 preterm infants were enrolled, including 59 cases (32.4%) in UU (+) group and 123 (67.6%) in UU (-) group. UU (+) group had significantly lower gestational age and birth weight and significantly higher incidences of vaginal delivery, premature rupture of membranes (PROM) >18 h and maternal chorioamnionitis than UU (-) group ( P<0.05). Compared with UU (-) group, UU (+) group had significantly higher leucocyte count, neutrophil count and interleukin-6 at 1, 24 and 72 h after birth ( P<0.05). No significant differences existed in C-reactive protein and procalcitonin between the two groups at each time point ( P>0.05). In UU (+) group, the incidences of intrauterine pulmonary infection and bronchopulmonary dysplasia (BPD) were higher and the incidence of respiratory distress syndrome was lower than UU (-) group ( P<0.05). No significant differences existed in the incidences of intraventricular hemorrhage, periventricular leukomalacia, feeding intolerance, necrotizing enterocolitis, retinopathy of prematurity between the two groups ( P>0.0 5). UU (+) group had significantly longer duration of oxygen therapy than UU (-) group ( P<0.05). No significant differences existed in the duration of invasive mechanical ventilation and hospital stay between the two groups ( P>0.05). Conclusions:Preterm infants <34 weeks with positive UU in respiratory tract secretions have higher incidences of vaginal delivery, PROM>18 h and maternal chorioamnionitis. Leukocyte and neutrophil count and interleukin -6 are higher in these infants. They need prolonged oxygen therapy and have increased risks of intrauterine pulmonary infection and BPD.

OBJECTIVE: To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells. METHODS: MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo. RESULTS: Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation. CONCLUSIONS Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Antineoplastic Agents ; Apoptosis ; Bortezomib ; Cell Line, Tumor ; Drug Synergism ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Proteolysis ; Proto-Oncogene Proteins c-bcl-2 ; Pyrroles

ObjectiveTo understand the usage of antibiotics in outpatients in a county of Zhejiang Province from 2015 to 2020， so as to provide a basis for further standardizing the clinical application of antibiotics in this region. MethodsOutpatient records and prescription records of 146 public medical institutions from 2015 to 2020 were extracted from the electronic medical record data sharing platform system of medical institutions in a county of Zhejiang Province. The utilization rates and the number of types of antibiotics used in outpatient patients were described. According to the drug anatomy， therapeutic and chemical classification system （ATC）， clinical application classification and dosage form， the use status of different types of antibiotics was observed. The annual percentage change （APC） was used to analyze the time trend of antibiotic use. Among the antibiotic prescriptions in each year， the proportions of prescriptions aimed for different use reasons and patients were compared to analyze the changes in the structures of antibiotic prescriptions. ResultsDuring 2015‒2020， a total of 2 861 438 prescriptions were issued in146 primary public medical institutions in this county， including 314 642 prescriptions for antibiotics， and the overall utilization rate of antibiotics was 11%. The utilization rate of antibiotics showed a decreased trend across the years （from 14.23% in 2015 to 7.59% in 2020，APC=-11.51%， 95%CI=-0.01%‒-21.7%， t=-12.05， P<0.001） and an obvious seasonal variation character （higher in winter and spring， lower in summer and autumn）. Cefoxitin sodium for injection was the most used antibiotic in 2015， and cefuroxime was the most used antibiotic from 2015 to 2020， respectively. The utilization rates of cephalosporins （APC=-11.06%， 95%CI=0‒-20.89%， t=-22.233， P<0.001）， quinolones （APC=-9.74%， 95%CI=0‒-18.53%， t=-7.652， P=0.002）， macrolides （APC=-17.52%， 95%CI=0‒-17.52%， t=-3.626， P=0.022） and lincoamides （APC=-49.01%， 95%CI=0‒-74%， t=-3.35， P=0.029） showed a decreasing trend across the years. There were differences in the distribution of drug use reasons （χ²=9 458.427， P<0.001）， as well as the age （χ²=5 421.709， P<0.001） and sex （χ²=245.322， P<0.001） of patients. During the observation period， 50.69% of antibiotic prescriptions were used to treat respiratory diseases， with the highest proportion of 57.67% in 2015 and the lowest proportion of 34.93% in 2020. 58.37% of patients were aged 50‒70 years， with a decreasing proportion of patients under 50 years （17.83% in 2015， 6.64% in 2020） and an increasing proportion of patients over 70 years （24.1% in 2015， 38.41% in 2020）. ConclusionThe utilization rate of antibiotics used in outpatients from primary public medical institutions in a county of Zhejiang Province shows a decreasing trend across the years， but higher than that of secondary and above hospitals in China， and also higher than that of primary medical institutions in economically-developed areas. The management and monitoring of the clinical use of antibiotics in the county should be actively strengthened.