Background: Twenty-four-hour urinary free cortisol (UFC) measurement is the initial diagnostic test for Cushing’s syndrome (CS). We compared UFC determination by both direct and extraction immunoassays using Abbott Architect, Siemens Atellica Solution, and Beckman DxI800 with liquid chromatography-tandem mass spectrometry (LC-MS/MS). In addition, we evaluated the value of 24-hr UFC measured by six methods for diagnosing CS. Methods: Residual 24-hr urine samples of 94 CS and 246 non-CS patients were collected.A laboratory-developed LC-MS/MS method was used as reference. UFC was measured by direct assays (D) using Abbott, Siemens, and Beckman platforms and by extraction assays (E) using Siemens and Beckman platforms. Method was compared using Passing–Bablok regression and Bland–Altman plot analyses. Cut-off values for the six assays and corresponding sensitivities and specificities were calculated by ROC analysis. Results: Abbott-D, Beckman-E, Siemens-E, and Siemens-D showed strong correlations with LC-MS/MS (Spearman coefficient r = 0.965, 0.922, 0.922, and 0.897, respectively), while Beckman-D showed weaker correlation (r = 0.755). All immunoassays showed proportionally positive bias. The areas under the curve were 0.975 for Abbott-D, 0.972 for LCMS/MS, 0.966 for Siemens-E, 0.948 for Siemens-D, 0.955 for Beckman-E, and 0.877 for Beckman-D. The cut-off values varied significantly (154.8–1,321.5 nmol/24 hrs). Assay sensitivity and specificity ranged from 76.1% to 93.2% and from 93.0% to 97.1%, respectively. Conclusions Commercially available immunoassays for measuring UFC show different levels of analytical consistency compared to LC-MS/MS. Abbott-D, Siemens-E, and Beckman-E have high diagnostic accuracy for CS.

【Objective】 To study the changes of platelet components(PC), apheresis platelets (AP) and pooled platelet concentrates (PPC) production of 19 provincial blood centers before and during the COVID-19 epidemic. 【Methods】 The data related to the collection of AP and the preparation of PPC from 2016 to 2021 of 19 provincial blood centers was collected. The production of PC, AP and PPC during the four years before the epidemic (i.e. 2016-2019) and during the COVID-19 epidemic (i.e. 2020 and 2021) were calculated respectively, and the change of production was analyzed. 【Results】 The total production of PC in 19 blood centers steadily increased from 2016 to 2019, with a decrease of 4.16% in 2020 and an increase of 15.60% in 2021, exceeding the output before the COVID-19 epidemic. In 2020, the production of PC of 42.11% (8/19) blood centers decreased compared with 2019, while 94.74% (18/19) in 2021 increased compared with 2020. The changes of AP output was basically consistent with the trend of PC. The total production of PPC in 2017 and 2018 both doubled compared to the previous year, while decreased by 67.98% in 2019, increased by 30.38% in 2020 and decreased by 27.08% in 2021. 【Conclusion】 The total production of PC kept increasing steadily between 2016 and 2019, but decreased in 2020 under the COVID-19 epidemic, with some blood centers being significantly affected. In 2021, with the strong support from government and various measures by blood centers, the total production of PC increased.

Severe muscle injury is hard to heal and always results in a poor prognosis. Recent studies found that extracellular vesicle-based therapy has promising prospects for regeneration medicine, however, whether extracellular vesicles have therapeutic effects on severe muscle injury is still unknown. Herein, we extracted apoptotic extracellular vesicles derived from mesenchymal stem cells (MSCs-ApoEVs) to treat cardiotoxin induced tibialis anterior (TA) injury and found that MSCs-ApoEVs promoted muscles regeneration and increased the proportion of multinucleated cells. Besides that, we also found that apoptosis was synchronized during myoblasts fusion and MSCs-ApoEVs promoted the apoptosis ratio as well as the fusion index of myoblasts. Furthermore, we revealed that MSCs-ApoEVs increased the relative level of creatine during myoblasts fusion, which was released via activated Pannexin 1 channel. Moreover, we also found that activated Pannexin 1 channel was highly expressed on the membrane of myoblasts-derived ApoEVs (Myo-ApoEVs) instead of apoptotic myoblasts, and creatine was the pivotal metabolite involved in myoblasts fusion. Collectively, our findings firstly revealed that MSCs-ApoEVs can promote muscle regeneration and elucidated that the new function of ApoEVs as passing inter-cell messages through releasing metabolites from activated Pannexin 1 channel, which will provide new evidence for extracellular vesicles-based therapy as well as improving the understanding of new functions of extracellular vesicles.
Creatine/metabolism* ; Extracellular Vesicles ; Muscle, Skeletal/metabolism* ; Myoblasts/metabolism* ; Regeneration ; Connexins/metabolism*

OBJECTIVE To establish and apply a method for simultaneous determination of the contents of dicentrine， protopine and coptisine in Tibetan Corydalis pallida of different origins， and to provide reference for origin determination and quality control of the kind of medicinal materials. METHODS Ultra performance liquid chromatography-tandem quadrupole mass spectrometry method was used. The determination was performed on Agilent EC-C18 column （100 mm×2.1 mm， 2.7 μm） with mobile phase consisted of acetonitrile-0.1% formic acid by gradient elution. The flow rate was 0.2 mL/min， and the column temperature was set at 35 ℃ . MS detection was carried out by electrospray ionization in positive modes， multiple reaction monitoring mode was used for quantitative analysis. RESULTS The injection mass concentrations of dicentrine， protopine， coptisine ranged from 5.88 to 117.60， 53.70 to 1 074.00， and 4.85 to 97.00 ng/mL， respectively， showing a good linear relationship with their respective peak areas （r＝0.998 2， 0.991 9， and 0.999 6， respectively）. The limits of quantitation were 2.35， 1.07 and 1.46 ng/mL； the limits of detection were 1.17， 0.54， 0.49 ng/mL， respectively. RSDs of precision， stability （24 h） and repeatability tests were all lower than 2.0％. The average recovery rates were 97.41%， 98.89% and 105.44%（ all RSDs＜5.0％， n＝6）. CONCLUSIONS The established method has good selectivity and high accuracy， and is suitable for the rapid analysis of dicentrine， protopine and coptisine in Corydalis. The total contents of three alkaloids in different original medicinal materials are from high to low in order of C. chrysosphaera， C. mucronifera， C. pygmaea， C. hendersonii and C. conspersa. The alkaloid contents in C. chrysosphaera and C. mucronifera are relatively similar， but no dicentrine has been detected in C. conspersa and C. hendersonii.

Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.

Objective To investigate the characteristics of hospitalized elderly schizophrenia patients combined with somatic diseases.Methods A cross-sectional study was conducted on hospitalized elderly schizophrenia patients using a questionnaire developed by ourselves at three mental health centers in Shanghai.Gender,age,length of education,course of disease,somatic diseases (hypertension,diabetes,hyperlipidemia,organic cerebral disease,and heart disease),antipsychotic medication as well as other relevant information were collected.Meanwhile,body mass index,body height and other relevant indexes were measured.Results Among 304 subjects,176 (57.9 ％) were complicated with somatic diseases,including 120 (39.5％) with hyperlipidemia,113 (37.2％) with hypertension and 78 (25.7％) with diabetes mellitus as the top three somatic diseases.Patients who were overweight or took atypical antipsychotics were more susceptible to somatic diseases (both P＜0.05);female patients were more susceptible to heart disease and diabetes than male patients (P ＜0.05);patients aged 70 years and over were susceptible to hypertension and hyperlipidemia than those under 70 years old (P＜0.05).Somatic diseases were related to age (over 70 years old),overweight and use of atypical antipsychotics in hospitalized elderly schizophrenia patients (P＜0.05).Conclusions The incidence of somatic diseases in hospitalized elderly schizophrenia patients is relatively high,and the most common somatic diseases are hyperlipidemia,hypertension and diabetes mellitus.Age,overweight and use of atypical antipsychotics are the influence factors for somatic diseases in these patients.

Objective To observe the anatomical and functional changes in patients with different degrees of myopic traction maculopathy (MTM) after vitrectomy.Methods It was a retrospective case series study.Forty-seven consecutive patients (47 eyes) diagnosed with MTM were studied between January 2010 and May 2014.There were 38 females (38 eyes) and 9 male (9 eyes),mean age was (65.13±6.98) years,mean axial length was (29.23±1.77) mm.The eyes was divided into 3 groups according to the macular morphologies on optical coherence tomography (OCT),including macular retinoschisis only group (MRS group,18 eyes),foveal retinal detachment group (FD group,13 eyes) and full-thickness macular hole group (MH group,16 eyes).All the eyes underwent minimum resolution angle in logarithmic (logMAR) best corrected visual acuity (BCVA),intraocular pressure,axial length,A or B-ultrasonography,fundus photography,OCT and microperimetry examinations.The average logMAR BCVA of 47 eyes was 1.43±0.52.The center retinal thickness (CRT) of eyes in MRS and FD group was (528.45± 167.61) μm.All the patients underwent pars plana vitrectomy combined with internal limiting membrane peeling.The mean follow-up period was 23.4 months.The changes of logMAR BCVA,microperimetry and macular microstructural were observed.Results At the final follow-up,the logMAR BCVA of 47 eyes was 0.86 ± 0.42,which improved compared with the preoperative vision (t=7.36,P＜ 0.001).The mean CRT of eyes in MRS and FD group was (250.90 ± 91.81) μm,which improved compared with the preoperative CRT (t=8.17,P＜0.001).In MRS group,the retina was attached in 18 eyes.In FD group,the retina was attached in 11 eyes,MH was observed in 2 eyes.In MH group,recurrent retinal detachment was observed in 1 eye.The differences of logMAR BCVA and retinal sensitivity among MRS,FD and MH groups were significant (x2 =6.38,11.08;P=0.030,0.004).Conclusion The macular structural and visual function in MTM eyes with macular retinoschisis only after vitrectomy are better than those in MTM eyes with MH and foveal retinal detachment.

Background: It remains controversial whether palliative primary tumor resection (PPTR) can provide survival benefits to the patients with metastatic colorectal cancer (mCRC) who have unresectable metastases. The aim of this study was to evaluate whether PPTR could improve the survival of patients with mCRC. Methods: We conducted a retrospective study on consecutive mCRC patients with unresectable metastases who were diagnosed at Sun Yat?sen University Cancer Center in Guangzhou, Guangdong, China, between January 2005 and December 2012. Overall survival (OS) and progression?free survival (PFS) after first?line chemotherapy failure were compared between the PPTR and non?PPTR patient groups. Results: A total of 387 patients were identified, including 254 who underwent PPTR and 133 who did not. The median OS of the PPTR and non?PPTR groups was 20.8 and 14.8 months (P < 0.001), respectively. The median PFS after first?line chemotherapy was 7.3 and 4.8 months (P < 0.001) in the PPTR and non?PPTR groups, respectively. A larger proportion of patients in the PPTR group (219 of 254, 86.2%) showed local progression compared with that of patients in the non?PPTR group (95 of 133, 71.4%; P < 0.001). Only patients with normal lactate dehydrogenase (LDH) levels and with carcinoembryonic antigen (CEA) levels <70 ng/mL benefited from PPTR (median OS, 22.2 months for the PPTR group and 16.2 months for the non?PPTR group; P < 0.001). Conclusions: For mCRC patients with unresectable metastases, PPTR can improve OS and PFS after first?line chemo?therapy and decrease the incidence of new organ involvement. However, PPTR should be recommended only for patients with normal LDH levels and with CEA levels <70 ng/mL.

Objective To explore the effect of pacifiers plus touching intervention on venipuncture-induced pains in newborn babies.Methods Ninety two neonates undergoing venous puncturing were randomly divided into touching intervention group and pacifiers plus touching group.During and after the venipuncture,the neonatal pain score,heart rate and blood oxygen saturation were compared between the two groups.Results The degree of pain perception in the pacifiers plus touching group was significantly lower than that in the only touching group(P<0.001).During and afterpuncturing the heart rate of the pacifiers plus touching group was significantly lower than that in the only touching group.However,the blood oxygen saturation was significantly higher(P<0.05). Conclusion Pacifiers plus touching can effectively relieve venipuncture-induced pains in neonates.

Objective To investigate the effects of cochlear implantation on residual hearing and to evaluate the potential impact of long -term electrical stimulations on residual hearing .Methods 58 hearing impaired children with cochlear implants were included in this study .All subjects could cooperate with behavioral audiometry .Audio-metric evaluations were carried out pre -implantation and 3 ,12 ,24 months post -implantation respectively .Of 58 subjects ,43 were followed up more than 1 year and 17 were followed up more than 2 years .Results All 58 subjects showed significant differences (P<0 .05) between pre- and 3 months post-implantation of residual hearing at the individual frequencies of 0 .25 ,0 .5 ,1 ,2 and 4 kHz .43 subjects followed up more than 1 year showed statistic differences (P<0 .05) between pre- and 3 months post -implantation ,pre- and 12 months post-implantation at 0 .25 ,0 .5 ,1 ,2 and 4 kHz respectively .Comparing 3 months with 12 months post -implantation ,there were sta-tistic differences at 0 .25 and 0 .5 kHz ,while no significant difference (P>0 .05) at 1 ,2 and 4 kHz .Of 17 subjects followed up more than 2 years ,there were significant differences (P<0 .05) between pre- and various return visits post-implantation .Post-implantation return visits ,there were significant differences between 3 months and 12 , 24 months at 0 .25 and 0 .5 kHz respectively ,not any significant differences on 1 ,2 and 4 kHz .There were no sig-nificant differences on each frequency between 12 months and 24 months post- implantation .Conclusion Residual hearing after cochlear implantation could decrease to some extent for various reasons .There were significant differ-ences between 3 and 12 months post-implantation at 0 .25 and 0 .5 kHz .Not any significant differences were ob-served between 12 months and 24 months post-implantation at each frequency .