Objective:To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China.Methods:Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed.Results:6 893 patients in CP ( n=6 453, 93.6%) or AP ( n=440, 6.4%) receiving initial imatinib ( n=4 906, 71.2%), nilotinib ( n=1 157, 16.8%), dasatinib ( n=298, 4.3%) or flumatinib ( n=532, 7.2%) -therapy. With the median follow-up of 43 ( IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance ( n=1 055, 15.3%), intolerance ( n=248, 3.6%), pursuit of better efficacy ( n=168, 2.4%), economic or other reasons ( n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph + ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph + ACA, poorer TFS; Ph + ACA, poorer OS. Conclusion:At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

Objective: To summarize the global research hotspots and trends of family intervention on autism spectrum disorder (ASD), to provide ideas for the development of localized research on family intervention for ASD in China. Methods: This study used the bibliometric software CiteSpace to conduct visual analysis on emerging cutting edge documents in the Web of Science core database in the field of family intervention for autism in the past 20 years (2001-2020). Data collection used 7 subject terms related to family caregiver intervention in February 2021. A total of 2 342 literature was obtained after data sorting. Results: The number of international publications has risen rapidly since 2013. The average annual number of international publications was 29 during 2001- 2012, then 250 during 2013-2020, which increased by 8 times. Among them, the United States ranked the top of publication with 1 295 articles, while publications from two universities in Canada and the United Kingdom showed higher impacts. The high frequency keywords that reflected the international hotspots included children, adolescent, mother, behavior, and stress; the high centrality keywords included follow up, intellectual disability, early recognition, young children and language. Conclusion The research hotspots in the field of ASD family intervention in the past 20 years included targets, strategies and forms, as well as the implementation effects of ASD family interventions. The trends of research in the past five years (2016-2020) mainly focus on the intervention studies of children, adolescents and adults with ASD and the randomized controlled trials of ASD family intervention focusing on caregivers.

Objective:To explore the role and mechanism of kidney brain protein (KIBRA) down-regulation in cognitive dysfunction caused by chronic cerebral hypoperfusion.Methods:Ninety male SPF grade Sprague Dawley (SD) rats were divided into four groups according to random number table: sham operation group ( n=15), chronic hypoperfusion group (2VO group, n=25), chronic hypoperfusion stereotaxic injection of AAV-KIBRA group (2VO+ AAV-KIBRA group, n=25), chronic hypoperfusion stereotaxic injection of AAV-Vector group (2VO+ AAV-vector group, n=25). Chronic cerebral hypoperfusion model was established by bilateral ligation of common carotid artery, and stereotactic injection of 2 μL AAV-KIBRA or AAV-vector was performed for 30 days.Morris water maze, in vitro electrophysiology, p21-activated kinase 3(PAK3) activity detection, Western blot, immunoprecipitation and Golgi staining were used to detect spatial learning and memory ability, long-term potentiation(LTP), KIBRA level expression, PAK3 activity changes and the distribution of dendritic spines.SPSS 16.0 statistical software was used for statistical data.One-way ANOVA was used to compare the differences between groups.LSD test was used to compare the significance of data differences between the two groups.Welch test was used for uneven variance. Results:After 1 month of chronic cerebral hypoperfusion, the level of KIBRA in the hippocampus of rats was detected by homogenate and Western blot, and it was found that the level of KIBRA in 2VO group was lower than that of sham group(73.49±4.12)% ( P<0.01). AAV-KIBRA injection in hippocampal CA1 region significantly up-regulated the level of KIBRA to (91.91±7.01)% over 2VO group ( P<0.01). Morris water maze test showed that the latency of the 2VO group(3rd-7th day trail data: (48.18±2.82)s, (43.45±2.27)s, (32.27±2.22)s, (26.55±2.37)s, (17.18±2.67)s) were significantly longer than those of the sham group((41.67±2.74)s, (32.58±2.57)s, (22.50±2.94)s, (16.91±2.39)s, (8.75±1.52)s) (all P<0.05), and the latencies of the 2VO+ AAV-KIBRA group 3rd-7th day trail data: (43.83±2.95)s, (35.25±2.15)s, (26.58±2.03)s, (19.92±2.17)s, (17.75±1.35)s) was significantly shorter than that of the 2VO group ((all P<0.01). The Morris water maze test with the platform removed showed that the latency of rats in the 2VO group to reach the platform region was significantly longer than that of the sham group, while the latency of rats in the 2VO+ AAV-KIBRA group to reach the platform region was significantly shorter than that in the 2VO group ( P<0.01). At the same time, the retention time and the crossing times in the platform region of 2VO group were less than those of the sham group ( P<0.01), but the retention time and the crossing times in the platform region of 2VO+ AAV-KIBRA group were significantly higher than those in the 2VO group ( P<0.01). The electrophysiological records of the brain slices showed that the relative excitatory postsynaptic field potential of 2VO group (1.43±7.43) was significantly lower than that of sham group (2.21±6.54) after high frequency stimulation, while the relative excitatory postsynaptic field potential of 2VO+ AAV-KIBRA group (1.90±8.15) was higher than that of 2VO group ( P<0.01). Immunoprecipitation in rat hippocampus revealed that PAK3 could be detected by Western blot assay when KIBRA was precipitated.The results showed that the relative enzyme activity of PAK3 in 2VO hippocampal tissue (0.64±0.04) was significantly lower than that in sham group (1.02±0.07), while the relative enzyme activity of PAK3 in 2VO+ AAV-KIBRA group (0.86±0.03) was significantly higher than that in 2VO group.Golgi staining showed that the density of dendritic spines in 2VO hippocampal neurons((6.85±0.43)/10 μm) was significantly lower than that in sham group((11.83±0.58)/10 μm), while the density of dendritic spines in 2VO+ AAV-KIBRA group((10.22±0.39)/10 μm) was significantly higher than that in 2VO group. Conclusion:The down-regulated of KIBRA after chronic cerebral hypoperfusion plays a key role in cognitive dysfunction and is also involved in the decrease of synaptic functional plasticity.The downregulation of KIBRA is involved in the structural plasticity of dendrites through the regulation of PAK3 activity.Therefore, KIBRA may be an important target for the prevention and treatment of cognitive function of chronic cerebral hypoperfusion.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.

Objective:To explore the effect of early quantitative pulmonary rehabilitation assessment in adult Intensive Care Unit (ICU) patients with mechanical ventilation in high altitude area.Methods:From March 2019 to October 2021, convenience sampling was used to select 287 adult ICU patients with mechanical ventilation of Qinghai Red Cross Hospital as the research object. According to the time of admission, the patients were divided into the control group (142 cases) and the experimental group (145 cases) . The control group was given the routine pulmonary rehabilitation, and the experimental group received the early pulmonary rehabilitation based on quantitative assessment. The Acute Physiology and Chronic Health EvaluationⅡ (APACHEⅡ) score and the Intensive Care Units Mobility Scale (IMS) score were compared between the two groups before enrollment, on the eighth and sixteenth days of pulmonary rehabilitation. The oxygenation index of the two groups of patients before enrollment and on the first, fourth, sixth, eighth and sixteenth days of pulmonary rehabilitation, the time of ICU stay, the time of mechanical ventilation, the success rate of ventilator removal and the complications of the two groups of patients with mechanical ventilation were also compared.Results:On the eighth and sixteenth days of pulmonary rehabilitation, the APACHE Ⅱ score of the experimental group was lower than that of the control group, and the IMS score was higher than that of the control group, with statistical differences ( P<0.05) . On the sixth, eighth and sixteenth days of pulmonary rehabilitation, the oxygenation index of the experimental group was higher than that of the control group, and the difference was statistically significant ( P<0.05) . The ICU stay time and mechanical ventilation time in the experimental group were lower than those in the control group, and the success rate of ventilator removal in the experimental group was higher than that in the control group, with statistical differences ( P<0.05) . Conclusions:Implementing early pulmonary rehabilitation for adult ICU patients with mechanical ventilation in high altitude area is conducive to promoting pulmonary rehabilitation of patients, improving the success rate of ventilator removal, and reducing patients' ICU stay time, mechanical ventilation time and the occurrence of complications.

Transjugular intrahepatic portosystemic shunt (TIPS) can effectively reduce the portal venous pressure and relieve the clinical complications related to portal hypertension. However, hepatic encephalopathy (HE) is still the main complication post TIPS. Studies have shown that patients over 65 years old with liver function reserve in Child-Pugh grade C are the high-HE-risk group post TIPS, and early TIPS treatment can benefit the survival of these high-risk patients. In this study, TIPS was used to treat 60 cases aged > 65 years old and liver function reserve in Child-Pugh grade C (decompensated liver cirrhosis) with esophagogastric variceal bleeding. The clinical results of 1-year was observed and the porto systemic gradient (PSG) was evaluated. The relationship between the incidence of HE and the PSG of patients with and without HE were compared to evaluate the effect of PSG on the incidence of HE.

Objective: To identify differentially expressed genes in the transcriptome of the lesional versus nonlesional skin tissues of patients with moderate and severe atopic dermatitis (AD) , and to elucidate their roles in the pathogenesis of AD. Methods: From July to October in 2016, lesional and nonlesional skin tissues were obtained from 5 outpatients of Han nationality with AD in Guangzhou Institute of Dermatology, Institute of Dermatology, Guangzhou Medical University. The next-generation high-throughput transcriptome-wide RNA sequencing (RNA-seq) was performed to identify differentially expressed genes, which were subjected to GO function annotation and KEGG pathway analysis. Real-time fluorescence-based quantitative PCR (qRT-PCR) was conducted to verify differences in candidate gene expression between lesional and nonlesional skin tissues. Results: An average of 10.96 GBs sequence reads were acquired among 10 samples. A total of 21 729 genes were detected, including 19 268 known genes and 2 545 predicted novel genes. A total of 23 153 new transcripts were detected, of which 18 889 were new alternative splicing subtypes of known protein-coding genes, 2 545 were transcripts belonging to new protein-coding genes, and the remaining 1 719 belonged to long-stranded non-coding RNA. Totally, 78 differentially expressed genes were identified between the lesional and nonlesional skin tissues, including 69 upregulated and 11 downregulated genes in the lesional skin tissues. Among them, there were several genes known to be associated with AD inflammation (CXCL1/2/8, IL6/IL1β, MMP1, SERPINB4, S100A2, GZMB, OASL, OSM) and barrier (KRT16, FABP5, CYP1A1) and keratinocyte differentiation (IL-20) . GO analysis revealed that functions of 72 differentially expressed genes could be annotated. KEGG pathway analysis showed that the differentially expressed genes were grouped into 132 signaling pathways, of which 13 were significantly enriched, including the interleukin (IL) -17 pathway, NOD-like receptor signaling pathway, Toll-like receptor signaling pathway, etc. qRT-PCR showed that the mRNA expression levels of candidate genes CXCL1, KRT6A, IL36A, SERPINB4 and PSAPL1 was consistent with the transcriptome sequencing results. Conclusions Differentially expressed genes and related important regulatory signaling pathways were identified between the lesional and nonlesional skin tissues of patients with AD at the transcriptional level, and the IL-17 pathway was found to be mostly enriched in AD lesions in patients of Han nationality. These findings provide an important basis for further study on the pathogenesis of AD..

OBJECTIVETo observe the clinical efficacy of acupuncture and moxibustion periodic therapy on folli-cular maldevelopment differentiated as spleen and kidneydeficiency.

METHODSSixty patients of follicular maldevelopment differentiated as spleen and kidneydeficiency were randomized as an observation group and a control group, 30 cases in each one. The conventional acupuncture-moxibustion therapy was used in the control group and the acupuncture-moxibustion periodic therapy was applied to the observation group. In the control group, the acupoints were selected in terms of spleen and kidneydeficiency, such as Guanyuan (CV 4), Qihai (CV 6), Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3), Xuehai (SP 10) and Zigong (EX-CA 1). In the observation group, the acupoints were selected in terms of the physiological characteristics of follicular phase, ovulatory phase, luteal phase and menstrual phase. The main acupoints were Zusanli (ST 36), Sanyinjiao (SP 6), Taixi (KI 3) and Xuehai (SP 10). The acupoints for benefiting kidneywere added in the follicular phase, such as Guanyuan (CV 4) and Dahe (KI 12), etc. The acupoints for regulatingand activating blood circulation were added in the ovulatory phase, such as Hegu (LI 4) and Taichong (LR 3), etc. The moxibustion was added for tonifying kidneyin the luteal phase, such as Qihai (CV 6) and Guanyuan (CV 4). The treatment was discontinued during the menstrual phase in the two groups. In the rest phases, acupuncture and moxibustion were given once every two days, 30 min each time. The overall efficacy, basal body temperature (BBT), follicular development, the average endometrial thickness and morphology as well as TCM syndrome score of spleen and kidneydeficiency were observed in the patients after 3-month menstrual periods. The adverse reactions were recorded in the two groups.

RESULTSIn the observation group, one case gave up the treatment due to the personal reason and another one stopped the treatment due to suffering from another kind of disease. 28 cases were included totally. In the control group, 3 cases were dropped out since attempting to receive in vitro fertilization-embryo transfer (IVF-ET) and 27 cases were finally included. The total effective rate was 92.9% (26/28) in the observation group, better than 85.2% (23/27) in the control group (<0.05). Except the endometrial morphology in the control group, after treatment, BBT, follicular development, the average endometrial thickness and morphology as well as TCM syndrome score were all improved apparently after treatment in the two groups (all<0.05). The improvements in follicular development, endometrial morphology and TCM syndrome score in the observation group were more obvious as compared with those in the control group (all<0.05). The incidence of the adverse reaction was 7.1% (2/28) in the observation group and was 3.7% (1/27) in the control group, indicating mild adverse reaction that could be relieved naturally.

CONCLUSIONSThe treatment with acupuncture and moxibustion achieves the significant efficacy on follicular maldevelopment differentiated as spleen and kidneydeficiency. Compared with conventional acupuncture-moxibustion therapy, the periodic therapy of acupuncture and moxibustion achieves the much better clinical efficacy.

OBJECTIVE:To investigate the compatibility stability of Fat-soluble vitamin (Ⅱ)/Water-soluble vitamin for in-jection with common electrolytes. METHODS:Referring to clinical common dose,Fat-soluble vitamin (Ⅱ) for injection/Wa-ter-soluble vitamin for injection collective packing [containing Fat-soluble vitamin(Ⅱ) for injection 2 ampoules and Water-soluble for injection 1 ampoule] were respectively mixed with Glucose injection,Potassium chloride injection,Concentrated sodium chlo-ride injection,Sodium bicarbonate injection,Potassium aspartate injection,Potassium aspartate and magnesium aspartate injection, Sodium glycerophosphate injection,Multi-trace elements injection (Ⅱ) to obtain mixture A-H. At room temperature (25 ℃),these mixtures were investigated in terms of appearance,pH value,osmotic pressure molar concentration and the number of insolu-ble particles at 0,1,2,3,4 h. The contents of bacterial endotoxin were tested at 0,4 h. RESULTS:Within 4 h after mixing, there was no significant change in appearance of those mixtures;pH value of mixture H changed greatly (RSD=5.13%,n=5), and that of mixture D and G increased significantly. The osmotic pressure molar concentration of those mixtures had no significantly change(RSD<2%,n=5)and lower than 600 mOsmol/kg. The bacterial endotoxin tests of those mixtures were negative. Two and four hours after mixing,the number of insoluble particles ≥10 μm in mixture B was increased significantly;2,3,4 h after mix-ing,the number of insoluble particles ≥10 μm in mixture E,F,H were increased significantly;0 ,1,2,3,4 h after mixing,the number of insoluble particles ≥10 μm in mixture G was increased significantly. There was statistical significance in the number of insoluble particle ≥10 μm in above mixtures compared to mixture A at the same time point(P<0.05),but it was in line with the standard of 2015 pharmacopeia. One,two,three and four hours after mixing,the number of insoluble particle ≥10 μm in mixture D was increased significantly,there was statistical significance compared to mixture A at the same time point(P<0.05);the num-ber of insoluble particle ≥10 μm in mixture D was beyond prescribed scope of pharmacopeia at 2,3,4 h after mixing. Within 4 h after mixing,both the number of insoluble particle ≥10 μm in mixture C and the number of insoluble particle ≥25 μm in edch mixture had no significant change,in accordance with pharmacopeia standard. CONCLUSIONS:Fat-soluble vitamin (Ⅱ)/Wa-ter-soluble vitamin for injection is not suitable for mixing with Multi-trace elements injection(Ⅱ),Sodium glycerophosphate injec-tion or Sodium bicarbonate injection due to great change of pH value and the number of insoluble particles.

Objective To understand the various HPV types and the factors influencing their distribution among women with normal cervical cytology in the Shanghai area, to provide basic data for cervical cancer prevention and vaccine use.Methods A questionnaire-based survey was conducted among 3 372 married women in the Shanghai area. A PCR reverse dot blot (PCR-RDB) method was adopted for HPV genotyping of cervical exfoliated cell samples from 3 206 women. Odds ratio (OR) for HPV infection were analyzed using logistic regression. Results Of the 3 206 women investigated, 669 (20.87%) were positive for HPV infection. The highest incidence of HPV infections was seen in the age groups of 55-59 years, 50-54 years and 45-49 years, with the rates of positive detection being 27.67%, 21.65%, and 21.55%, respectively. While 70.4% of the positive cases had a single infection, 29.6% showed multiple infections. In cases with multiple infections, double infection was predominant (20.63%). The top five high-risk gene types were HPV52(3.65%),HPV53(2.71%),HPV51(2.03%),HPV58(1.87%),and HPV16 (1.40%). The top three low-risk gene types were HPV81 (2.03%), HPV42 (1.43%), and HPV55 (1.31%). Among the women with HPV infections,there were 483 having medium-high-risk HPV infection.There were significant differences in the age,the age at first sexual activity,sexual activities per week,education,and alcohol consumption between HPV positive and HPV negative patients. Age stratification showed that the infection rates in the 55-59 years old group were significantly higher than that in the other age groups(χ2=15.349, P=0.000). Both single factor and multivariate non-conditional logistic regression analyses showed that higher education and the start of sexual activity at a later age were protective factors for medium-high-risk HPV infection,with regression coefficients of-0.165 and-0.08,respectively (P<0.01) in the multivariate analysis. The risk factors included age between 55- 59 years, menstrual status (menopause), sexual activity (≥3 times per week) and alcohol consumption. High-risk HPV infections also had the same risk factors,and the odds ratios were 1.558,1.275,and 1.678,respectively(P<0.01).However, 55-59 years of age and alcohol consumption are independent risk factors for medium-high risk HPV infection. Conclusions High-risk HPV in women of Shanghai is commonly caused by HPV52, HPV53, HPV51,HPV58,and HPV16.The high-risk group includes women who are 55-59 years old.While drinking is an independent risk factor for medium-high risk HPV infection, a moderate sex life and delayed age at first sex can reduce the risk of high-risk HPV infections.