Objective To observe the efficacy and safety of repetitive transcranial magnetic stimulation(rTMS)on refractory tinnitus and the differences of resting-state functional magnetic resonance imaging(rs-fMRI)imaging between before and after treatment,and to explore the possible central mechanism of rTMS regulation of tinnitus.Methods Thirty-seven patients with refractory tinnitus admitted in Affiliated Hospital of North Sichuan Medical College from September 2022 to February 2023 were selected and were divided into experimental group(n=20)and control group(n=1 7).The experimental group was given true rTMS treatment,and the control group was given sham stimulation with the same parameters.Tinnitus handicap inventory(THI)score,tinnitus loudness visual analogue scale(VAS)score and rs-fMRI scan were performed before and after treatment.Regional homogeneity(ReHo)was calculated after scanning,and the different brain regions were selected as the area of interest(ROI)and the whole brain functional connection(FC)was performed.Results There were no significant differences in age,gender,education level,tinnitus side,course of disease,hearing level,self-rating depression scale,self-rating anxiety scale the experimental group and control group.There were no significant differences in THI and VAS scores between the two groups before treatment;the THI and VAS scores in the experimental group decreased after 2 weeks of rTMS treatment(P＜0.001),while there was no significant difference in the two scores in the control group before and after treatment.Only 3 patients in the experimental group experienced left facial muscle tremor or transient mild scalp pain during treatment,without other serious side effects.The ReHo of the left cerebellar area 9 increased in the experimental group after rTMS(P＜0.005);the ReHo values in the right inferior temporal gyrus,left posterior central gyrus and left anterior central gyrus increased in the control group after intervention(P＜0.005).The FCs between the right inferior temporal gyrus and the left orbital inferior frontal gyrus,the left anterior cingulate gyrus increased in the experimental group(P＜0.005),and FC between the right inferior temporal gyrus and the left superior marginal gyrus decreased(P＜0.005).The FCs between the right cuneus and the left fusiform gyrus,right superior occipital gyrus decreased in the experimental group after rTMS(P＜0.005).The FC between the right cuneus and the left fusiform gyrus increased in the control group after intervention(P＜0.005),while other FCs remained unchanged.Conclusions rTMS has a certain therapeutic effect on refractory tinnitus with higher safety;regulation of auditory brain network and related non-auditory brain network may be one of the central mechanisms of rTMS treating refractory tinnitus.

[Objective]To evaluate the efficacy and safety of total oral regimens containing pomalidomide as a second-line treatment strategy in multiple myeloma.[Methods]A total of 22 patients with multiple myeloma placed on total oral regimens containing pomalidomide as a second-line therapy from March 2020 to December 2023 were retrospectively analyzed to evaluate the treatment response,survival and safety.[Results]The median age of the 22 patients was 71.5 years old. The total oral treatment regimens containing pomalidomide included IPD (7 cases),PCD (11 cases),XPD (2 cases),and PD (2 cases). The median number of treatment cycles was 14. Among the 13 patients with prior lenalidomide exposure,ORR was 53.85％,of which 23.08％ was ≥VGPR. In 9 patients without prior lenalidomide exposure,the ORR was 77.78％,and of which 55.56％ was ≥VGPR. There was no significant difference in ORR between these two groups (P=0.38). In 12 patients with high genetic risk,the ORR was 50％,and ≥VGPR was 16.67％. The median follow-up time was 10.6 months. Disease progressed in 10 patients and death occurred in 6 patients of them. The median progression free survival (PFS) was not reached (not reached and 10.6 months in non-lenalidomide-exposure patients or lenalidomide-exposure patients,respectively).The high grade treatment-related adverse events (AEs)(≥3 ) were reported in 18.18％ patients,including granulocytopenia,thrombocytopenia,and pulmonary infection. There was no treatment-related death.[Conclusion]Total oral regimens containing pomalidomide as a second-line therapy is generally effective and safe for multiple myeloma patients.

The mechanism of tinnitus remains undear.Currently,in addition to tinnitus induced by ear disea-ses,various systems of the body are also involved in the pathogenesis of tinnitus.Obstructive sleep apnea hypopnea syndrome(OSAHS)may be related to tinnitus,which has garnered increasing attention in recent years.This article reviews the latest research progress on the occurrence and possible mechanism of tinnitus in OSAHS,shedding new light on the treatment of tinnitus.

Objective: To establish a microwave digestion-inductively coupled plasma mass spectrometry assay for simultaneous determination of multiple elements in placenta. Methods: Fresh placental tissues were dried at 60 ℃ for 15 h and ground into power. Then, 0.3 g homogenized samples were digested in a microwave digestion system. The interference from mass spectrometry was removed using the kinetic energy discrimination model in the inductively coupled plasma mass spectrometry, and the baseline interference was removed by online internal standards. The contents of 17 elements were determined in placental specimens using the established microwave digestion -inductively coupled plasma mass spectrometry assay, including V, Ni, Co, Fe, Cr, Cu, Zn, Mn, As, Sn, Sb, Ba, Se, Cd, Pb, Hg and Tl. Results: Good linearity was shown for V, Ni, Co, Cr, As, Se, Cd, Pb and Tl at 1 to 50 µg/L, Fe at 100 to 5 000 µg/L, Zn, Cu, Mn and Ba at 10 to 500 µg/L, Sn and Sb at 0.1 to 5 µg/L, and Hg at 0.2 to 2 µg/L, with all correlation coefficients of 0.999 8 and higher. The detection limits of these 17 elements ranged from 0.5 to 100 μg/kg, with relative standard deviations of 2.1% to 6.5%, and recovery rates of 83.3% to 110.0%. The determination results of 17 elements were all within the normal reference range defined in the certified reference materials of chicken (GBW10018). Conclusions The microwave digestion-inductively coupled plasma mass spectrometry established based on optimized pretreatments and mass spectrometry detection conditions, is feasible for simultaneous determination of multiple elements in placenta.

OBJECTIVE To establish the fingerprint of Tibetan medicine Adhatoda vasica ，and determine the contents of vasicine and vasicinone ，so as to comprehensively evaluate its quality combined with chemical pattern recognition. METHODS Using vasicine as control ，HPLC fingerprints of 11 batches of A. vasica were established with Similarity Evaluation System for Chromatographic Fingerprints of TCM （2012 edition）. The common peaks were identified and their similarities were evaluated. Cluster analysis （CA），principal component analysis （PCA）and orthogonal partial least squares-discriminant analysis （OPLS-DA） were performed by using SPSS 25 software and SIMCA 14.1 software. The variable importance in the projection （VIP）value＞1.0 was used as the standard to screen the differential components affecting the quality of A. vasica ；the contents of vasicine and vasicinone were determined by HPLC simultaneously. RESULTS A total of 23 common peaks were found ，and peak 2 was identified as vasicine ，and peak 4 was identified as vasicinone. Their similarities ranged 0.920-0.994. The results of CA showed that 11 batches of samples were clustered into 3 categories（distance was 14）：S1-S8 as one category （origin：Yunnan，Tibet），S9 as one category （origin：Yunnan），S10-S11 as one category （origin：Sichuan）；the results of P CA and OPLS-DA showed that S 9 and S10-S11 were divided into one category respectively ，and S1-S8 were further divided into 2 categories：S1，S4 as one category，S2-S3，S5-S8 as one category ；the common peaks with VIP value ＞1.0 included peak 2，peak 16，peak 21，peak 17，peak 1 and peak 13. Among 11 batches of samples ， contents of vasicine and vasicinone were 4.12-10.22 and 0.60-3.26 mg/g， respectively. CONCLUSIONS Established edu.cn HPLC fi ngerprint and content determination method are simple and accurate ，and can be used for the quality evaluation of Tibetan medicine A. vasica ，by combining with chemical pattern recognition. Vasicine and other components may be the differential components that affect the quality of the drug.

Objective:To evaluate the prognostic value of extravascular lung water index (EVLWI) , soluble intercellular adhesion molecule-1(sICAM-1) and Krebs yon den lungen-6 (KL-6) in severe pneumonia patients with Severe Acute Respiratory Syndrome (ARDS).Methods:A prospective study was conducted in Respiratory Intensive Care Unit of the Affiliated Zhengzhou Central Hospital of Zhengzhou University from October 2017 to February 2020. The study included 65 severe pneumonia patients with ARDS, who was performed by measurement of pulse index continuous cardiac output and survived more than 3days after admission. The Extravascular Lung Water Index (EVLWI) , sICAM-1, KL-6 and Oxygenation Index(OI) on 1st, 3rd and 5th day were detected. APACHEⅡ score, patient survival events (days) and survival outcome were recorded. Correlation analysis between EVLWI, sICAM-1, KL-6 and OI was performed on the 1st, 3rd and 5th day after admission. Independent risk factors of mortality in severe pneumonia patients with ARDS were analyzed by multiple logistic regression. Receiver operating characteristic curve was drawn, and the prognostic value of each parameter was assessed finally.Results:The PCT, EVLWI, sICAM-1, KL-6 and APACHEⅡ score in the death group were significantly higher than those in the survival group ( P<0.05) at RICU admission, and the length of RICU stay was significantly shorter than that in the survival group ( P<0.05), while differences in other clinical characteristics between two groups were not statistically significant ( P>0.05) . These parameters including levels of EVLWI, sICAM-1, KL-6, Procalcitonin and APACHE Ⅱscore in the death group were significantly higher than those in the survival group on the 1st, 3rd and 5th day ( P<0.05), whereas the OI was significantly lower than that of the survival group on the 3rd and 5th day ( P<0.05). Logistic regression analysis showed that EVLWI, sICAM-1, KL-6 level were significantly related with the mortality of these patients. The levels of sICAM-1, kl-6 and EVLWI on 1st, 3rd and 5th day after RICU admission showed a significant negative correlation with OI ( P<0.001). Whereas, The levels of sICAM-1, kL-6 on 1st, 3rd and 5th day showed a significant positive correlation with EVLWI ( P<0.001). The sensitivity and specificity of sICAM-1, KL-6 combined with EVLWI in prognosis evaluation on 1st, 3rd and 5th day were 75.0%, 84.4%, 85.0%, 66.7%, 80.0%, 86.7%, respectively. The AUC was 0.864, 0.881, 0.892 on 1st, 3rd and 5th day, respectively ( P<0.001), which had a better prognostic value than each of them. Conclusions:EVLWI, sICAM-1 and KL-6 were independent risk factors for the prognosis of severe pneumonia patients with ARDS. The combination of EVLWI, sICAM-1 and KL-6 might be important in early predicting the prognosis of the 28d mortality.

Objective:To analyze the epidemiological and clinical characteristics of imported COVID-19 cases after SARS-CoV-2 vaccination and to provide evidence for the prevention and control of COVID-19.Methods:The imported COVID-19 cases in Chengdu as of April 15, 2021 were divided into the vaccinated group and unvaccinated group according to the history of SARS-CoV-2 vaccination. The epidemiological and clinical data of the cases were collected retrospectively, and the differences in epidemiological and clinical characteristics of the two groups were compared. Laboratory tests consisted of nucleic acid test, clinical index test, serum antibody test and lymphocyte test. Software WPS2019 was used for data management and software R 4.0.3 was used for statistical analysis.Results:A total of 75 COVID-19 cases were included in the analysis, in which 20 had received SARS-CoV-2 vaccination and only 4 with clinical symptoms, 55 patients did not receive SARS-CoV-2 vaccination, and 16 had clinical symptoms. In vaccinated group, the first injection time of vaccination ranged from July to November 2020, and 10 cases received two doses of vaccine simultaneously and 10 cases received two doses of vaccine at intervals of 14-57 days. The intervals between the completion of vaccination and the onset ranged from 87 days to 224 days. The differences in classification and clinical type between the two groups were significant. Significant differences were observed in case classification and clinical type between vaccinated group and unvaccinated group ( P<0.05). The vaccinated group had a relatively high proportion of asymptomatic infections (40.00%, 8/20), while mild infections were mainly observed in the unvaccinated group(76.36%,42/55). The differences in Ct values (ORF1ab gene and N gene) at the diagnosis were not significant between vaccinated group and unvaccinated group ( P>0.05), similar results were also observed in lymphocyte subtypes, procalcitonin and C-reactive protein level comparisons. Serum amyloid A level was higher in unvaccinated group than in vaccinated group ( P<0.05). However, the SARS-CoV-2 related serum antibody of IgM, IgG and total antibody levels were significantly higher in vaccinated group ( P<0.05). Conclusions:Risk of infection still exists with SARS-CoV-2 after vaccination, which can facilitate the production of specific serum antibody of IgM and IgG when people are exposed to the virus. It has a certain protective effect on SARS-CoV-2 infected persons. Vaccination can reduce the clinical symptoms and mitigate disease severity.

Objective:To explore the MRI features of neonatal deep cerebral arterial infarctions.Methods:The medical and MRI datas of 23 neonates with deep cerebral arterial infarctions from January 2011 to December 2018 in Beijing Children′s Hospital, Capital Medical University were retrospectively analyzed. Both 11 males and 12 females with ages between 1-28 d were recruited and MRI were performed within 2-20 d after symptom onset. The MRI featurs including location, morphology, signal characteristics, enhancement features and other accompanied signs were reviewed.Results:A total of 15 cases with arterial infarction and 8 cases with complication of purulent meningitis were identified. The median age at presentation were 2 d and 7 d respectively. The unilateral involvement were demonstrated in all neonates with arterial infarctions. Among them, 11 had deep infarcts and the main branch of the middle cerebral artery was involved in 4 neonates. MRI showed slightly hypo-intensity on T 1WI and slightly hyper-intensity on T 2WI with indistinct boundary and focal punctate hyper-intensity on T 1WI and hypo-intensity on T 2WI. In 8 cases secondary to purulent meningitis, unilateral involvement was found in 5 cases and bilateral involvement in 3 cases. All cases showed hypo-intensity on T 1WI and hyper-intensity on T 2WI with indistinct boundary. Among them, 7 cases were heterogeneous, with small cystic changes which appeared as slightly hyper-intensity on T 1WI and slightly hypo-intensity on T 2WI peripherally, as well as nodular or patchy restricted diffusion. Marked swelling of the lesion was found in 6 cases. Multiple patchy or ring enhancement was revealed in 5 cases. Iso-intensity and restricted diffusion in posterior horn of the lateral ventricle were found in 2 cases. Restricted diffusion in frontotemporal subarachnoid space was found in 5 cases. One case showed subdural effusion. Conclusion:Neonatal deep cerebral arterial infarctions have certain characteristic appearance on MRI. Lesions secondary to purulent meningitis can be bilateral involvement with heterogeneous MRI intensities, and different period of infarction signs could be found concurrently. MRI is beneficial to the differential diagnosis.

Objective: To learn the human resource development of provincial,municipal and county-level centers for disease control and prevention（CDCs）in Zhejiang Province from 2010 to 2017,and to provide evidence for optimizing human resource allocation . Methods: We obtained the human resource data of CDCs in Zhejiang Province from national information system for disease control and prevention,and analyzed the changes in the number of permanent staffs,the number of permanent staffs per ten thousand permanent residents as well as the composition of the age,education level,professional background and title in provincial,municipal and county-level CDCs from 2010 to 2017 . Results: The number of the permanent staffs of CDCs in Zhejiang Province increased from 4 592 to 4 835 from 2010 to 2017. In 2017,the number of permanent staffs in overall,provincial,municipal and county-level CDCs per ten thousand permanent residents were 0.855,0.068,0.186 and 0.600,respectively,all of which did not meet the standard. The main age group of CDC staffs changed from 25-34 years old in 2010 to 35-44 years old in 2017. The staffs of overall,provincial,municipal and county-level CDCs mainly had Bachelor's degrees in 2010,while the staffs of provincial CDCs mainly had Master's degrees and above in 2017. The percentages of staffs who had Bachelor's degrees and above in overall,provincial,municipal and county-level CDCs in 2017 increased to 75.12%,90.36%,80.76% and 71.65%,respectively. The CDC staffs were mainly public health professionals,and the percentage increased from 2010 to 2017. The percentages of public health and laboratory medicine professionals in overall,provincial,municipal and county-level CDCs in 2017 increased to 71.56%,79.17%,70.14% and 71.15%,respectively. The CDC staffs mainly had intermediate title,and the percentage of senior title in overall,provincial,municipal and county-level CDCs in 2017 increased to 25.58%,38.80%,32.99% and 21.79%,respectively . Conclusion From 2010 to 2017,the structure of education level,professional background and title of CDC staffs in Zhejiang Province were further optimized,but there was a lack of permanent staffs and a decrease in the staffs under 35 years old.

Health impact assessment（HIA）is an evidence-based methodology to assess the potential impacts of a policy,program or project and to make recommendations for health improvement. HIA can promote the cooperation between health and non-health sectors,raise the awareness about health in decision-makers,increase the participation of stakeholders and change health inequality. This paper reviews the international studies into HIA from 2000 to 2018,providing reference for HIA development in China.