Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To analyze the metabolomics characteristics of chronic atrophic gastritis(CAG)patients with liver-stomach qi stagnation and spleen-stomach weakness syndromes based on non-targeted metabolomics technology,and to identify the serum differentiated metabolites related to traditional Chinese medicine(TCM)syndrome of CAG patients,so as to provide a reference for the objectification of syndrome differentiation.Methods Sixty patients with CAG were included,including 30 cases of liver-stomach qi stagnation syndrome and 30 cases of spleen-stomach weakness syndrome.Fasting blood of 5 mL was collected from the cubital vein of patients in the two groups,and the serum levels of metabolites were detected by ultra-high-performance liquid chromatography-mass spectrometry(UPLC-MS)methods.The principal component analysis(PCA),orthogonal partial least squares-discriminant analysis(OPLS-DA),and cluster analysis were used to screen the differentiated metabolites of CAG patients with liver-stomach qi stagnation syndrome and spleen-stomach weakness syndrome.Finally,metabolite pathway analysis was performed for the obtained differentiated metabolites using the KEGG database.Results The results for the screening of differentiated metabolites showed that significant differences of amino acid derivatives and small peptide metabolites were presented between CAG patients with liver-stomach qi stagnation syndrome and CAG patients with spleen-stomach weakness syndrome.The amino acid derivatives consisted of N-acetylglycine,histamine,O-phosphoserine,selenomethylselenocysteine,and methyl-tyrosine.And the small peptide metabolites consisted of tyrosine-leucine-phenylalanine,histidine-alanine-glutamate-lysine,L-asparagine-L-proline-L-serine,and L-isoleucine-L-isoleucine.Conclusion Differences in amino acid metabolism exist between CAG patients with liver-stomach qi stagnation syndrome and those with spleen-stomach weakness syndrome,and metabolites such as N-acetylglycine,intermethyltyrosine,and O-phosphoserine may be the potential biomarkers for distinguishing liver-stomach qi stagnation syndrome from spleen-stomach weakness syndrome in CAG patients.

ObjectiveTo explore the value of plasma free metanephrines， including metanephrine（MN） and normetanephrine（NMN）， collectively referred to as MNs in the diagnosis of pheochromocytoma and paraganglioma （PPGL）. MethodsThe study included 1 631 patients suspected of PPGL from December 2014 to December 2020 in SunYat-sen Memorial Hospital. In these subjects， Plasma free MNs were measured by liquid chromatography-tandem mass spectrometry（LC-MS/MS） before surgery. Receiver operating characteristic （ROC） curves were used to determine the sensitivity and specificity of plasma NMN and MN in the diagnosis of PPGL. ResultsOf the screened patients， 108 patients had pathologically confirmed PPGL and 1 523 patients had definitive diagnoses other than PPGL as a control group. The median value of plasma MN ［0.54（0.17~4.48） nmol/L vs. 0.15（0.11~0.21） nmol/L， P<0.001］ and NMN ［7.48（2.12~15.01） nmol/L vs. 0.32（0.22~0.46） nmol/L， P<0.001］ were significant higher in the PPGL group than in the control group. Using an upper cut-off of 0.395 nmol/L for MN， the sensitivity was 60.2% and the specificity was 97.8%； when using a cut-off of 1.105 nmol/L for NMN， the diagnostic sensitivity was 87.0%， and the specificity was 98.7%. The area under the ROC curve and 95% confidence interval of plasma MN and NMN combined were 0.800（0.743， 0.858）， 0.959（0.932， 0.98） and 0.970（0.944， 0.996）， respectively. Analyzing the false-positive results， it was found that in the control group， 3% of the false-positive cases appeared. The estimated glomerular filtration rate（eGFR） were significantly lower in the false-positive group than in the true-negative group ［74.42（51.04~96.96） mL/min vs. 88.51（72.80~101.83） mL/min， P=0.001］. In 212 patients with eGFR lower than 60 mL/min， the false positive rate was increased to 8%. If the upper limit of the reference interval was increased by 25%， the specificity was increased to 96.7%； when the upper limit of the reference interval was increased by 50%， the specificity was 98.6 %. ConclusionsPlasma free MNs has a great reliability in the diagnosis of PPGL. The negative predictive value is extremely high and close to 100%. Combination analysis of plasma MN and NMN can further improve diagnostic performance. However， a few false positive cases may appear and might be influenced by impaired renal function. In patients with eGFR lower than 60 mL/min， the false positive rate is significantly increasing， which need a 25%-50% increase in the expected upper limit of a reference range to guarantee high specificity.

OBJECTIVE: To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA). METHODS: A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also. RESULTS: A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study. CONCLUSIONS CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).
Humans ; Medicine, Chinese Traditional ; Osteoarthritis, Knee/therapy* ; Outpatients ; Quality of Life ; Treatment Outcome

【Objective】 To explore the clinical value of urinary aldosterone concentration(UAC) in primary aldosteronism(PA) screening and to evaluate the consistency of the two methods, liquid chromatography tandem mass spectrometry(LC-MS/MS) and chemiluminescence immunosorbent assay(CLIA), for determining UAC. 【Methods】 Among the 133 patients with suspected PA enrolled from October 2018 to August 2019, 55 were diagnosed with PA(30 with aldosteroneproducing adenoma and 25 with bilateral idiopathic hyperplasia) and 78 with essential hypertension(EH). Parallel determination of UAC was done with LC-MS/MS and CLIA assays on all subjects, then we compared the two methods and evaluated their correlation and consistency. Reciever operating characteristic(ROC) analysis was applied to assess the diagnostic accuracies, area under the curve(AUC) and cutoff values of UAC, plasma aldosterone concentration(PAC), random aldosterone to renin ratio(ARR) and urine aldosterone to renin ratio(UARR). Furthermore, ROC analysis of high urine sodium subgroup(urine sodium≥130 mmol/24h) was performed to evaluate the impact of sodium intake on PA screening. 【Results】 ①UACCLIA and UACLC-MS/MS were positively correlated(r=0.69, P < 0.001). Bland-Altman analysis showed poor consistency between CLIA and LC-MS/MS. ②The diagnostic efficiency of UAC and PAC in PA screening was equivalent (P > 0.05), while ARR was more efficient than UAC and PAC(P < 0.0001). AUC of UACCLIA, UACLC-MS/MS, PAC and ARR was 0.739, 0.659, 0.723, 0.943, respectively. The cutoff values for them were 5.1 μg/24 h, 11.6 μg/24 h, 27.6 ng/dL and 23.2 ng·dL^-1(/ μg·L^-1·h^-1), respectively. ③Both UARRCLIA and UARRLC-MS/MS performed as well as ARR in PA screening. AUC of UARRCLIA was 0.924 at the cutoff value of 1.75 μg·24h^-1(/ μg·L^-1·h^-1). While AUC of UARRLC-MS/MS was 0.906 at the cutoff value of 4.63 μg·24h^-1(/ μg·L^-1·h^-1). AUC of UACLC-MS/MS in high urine sodium subgroup was 0.708 at the cutoff of 14.9 μg/ 24 h. ④The diagnostic efficiency of UAC made no difference after sodium intake increased to 130 mmol/24 h or higher. 【Conclusion】 UAC alone is of little clinical value compared to ARR in PA screening and can serve as a supplementary indicator currently. But UARR, a combintion of UAC and plasma renin activity(PRA), is as valuable as ARR for screening PA. The optimal cutoff values of UACLC-MS/MS and UACCLIA are 11.6 μg/24 h, 5.1 μg/24 h, respectively. The optimal cutoff values of UARRLC-MS/MS and UARRCLIA are 4.63 μg·24 h^-1/(μg·L^-1·h^-1) and 1.75 μg·24 h^-1/(μg·L^-1·h^-1), respectively. Besides, significant bias of UAC observed in CLIA and LC-MS/MS results indicates that appropriate definition of cutoff value and reference range for each method are mandatory.

adrenocorticalcarcinoma；cortisolhypersecretion；hypokalemia；prognosis 【Objective】To analyze the prognostic determinants of adreno cortical carcinoma（ACC）inadults.【Methods】Alladult patients who were admitted to SunYat-sen Memorial Hospital，SunYat-sen University from December 2011 to March 2017 and pathologically diagnosed ACC were included in this study.Thec linical data and preoperative laboratory examinations of those patients were analyzed retrospectively. Overall survival or disease-free survival was calculated and survivalcurves were plotted by Kaplan-Meier and compared by log-rank test. Harzardratios（HRs） with their 95% confidenceintervals（CIs） were calculated by univariate and multivariate Coxregression model.【Results】The study included 20 adult patients with ACC， with a median follow-up of 13months （6~73 months）. The mean survival time of those patients was 49.2 months（6~73months），with a 1-year survival rate of 70.0%. The results of multivariate Coxregression analysis revealed that the presense of cortisol hypersecretion（HR=23.60，95%CI：2.49-223.79，P=0.006） and hypokalemia（HR=23.60，95%CI：2.49-223.79，P=0.006）were predictors of poorprognosis of ACC. Moreover，in 18 patients with completely resected ACC，the presense of hypokalemia resulted in a worse disease-free survival.【Conclusion】The presense of cortisol hypersecretion and hypokalemiaare independent risk factors associated with poorprognosis of ACC in adults.​

OBJECTIVETo evaluate the effect and safety of Kuanxiong Aerosol (, KA) on patients with angina pectoris.

METHODSBlock randomization was performed to randomly allocate 750 patients into KA (376 cases) and control groups (374 cases). During an angina attack, the KA group received 3 consecutive sublingual sprays of KA (0.6 mL per spray). The control group received 1 sublingual nitroglycerin tablet (NT, 0.5 mg/tablet). Log-rank tests and Kaplan-Meier estimations were used to estimate the angina remission rates at 6 time-points after treatment (1, 2, 3, 4, 5, and >5 min). Logistic regression analysis was performed to observe the factors inflfluencing the rate of effective angina remission, and the remission rates and incidences of adverse reactions were compared for different Canadian Cardiovascular Society (CCS) classes of angina.

RESULTSThe 5-min remission rates in the KA and control groups were not signifificantly different (94.41% vs. 90.64%, P>0.05). The angina CCS class signifificantly inflfluenced the rate of remission (95% confidence interval = 0.483-0.740, P<0.01). In the CCS subgroup analysis, the 3-and 5-min remission rates for KA and NT were similar in the CCSII and III subgroups (P>0.05), while they were signifificantly better for KA in the CCSI and II subgroups (P<0.05 or P<0.01). Furthermore, the incidence of adverse reactions was signifificantly lower in the KA group than in the control group for the CCSII and III subgroups (9.29% vs. 26.22%, 10.13% vs. 20.88%, P<0.05 or P<0.01).

CONCLUSIONSKA is not inferior to NT in the remission of angina. Furthermore, in CCSII and III patients, KA is superior to NT, with a lower incidence of adverse reactions. (Registration No. ChiCTRIPR-15007204).

Aerosols ; adverse effects ; therapeutic use ; Angina Pectoris ; drug therapy ; Case-Control Studies ; Drugs, Chinese Herbal ; adverse effects ; therapeutic use ; Female ; Humans ; Kaplan-Meier Estimate ; Logistic Models ; Male ; Middle Aged ; Remission Induction ; Treatment Outcome

OBJECTIVE: To noninvasively assess the neurodegenerative changes in the brain of patients with Niemann-Pick type C (NPC) disease by measuring the lesion tissue with the iterative decomposition of water and fat with echo asymmetry and least square estimation-iron quantification (IDEAL-IQ). MATERIALS AND METHODS: Routine brain MRI, IDEAL-IQ and 1H-proton magnetic resonance spectroscopy (1H-MRS, served as control) were performed on 12 patients with type C Niemann-Pick disease (4 males and 8 females; age range, 15–61 years; mean age, 36 years) and 20 healthy subjects (10 males and 10 females; age range, 20–65 years; mean age, 38 years). The regions with lesion and the normal appearing regions (NARs) of patients were measured and analyzed based on the fat/water signal intensity on IDEAL-IQ and the lipid peak on 1H-MRS. RESULTS: Niemann-Pick type C patients showed a higher fat/water signal intensity ratio with IDEAL-IQ on T2 hyperintensity lesions and NARs (3.7–4.9%, p < 0.05 and 1.8–3.0%, p < 0.05, respectively), as compared to healthy controls (HCs) (1.2–2.3%). After treatment, the fat/water signal intensity ratio decreased (2.2–3.4%), but remained higher than in the HCs (p < 0.05). The results of the 1H-MRS measurements showed increased lipid peaks in the same lesion regions, and the micro-lipid storage disorder of NARs in NPC patients was detectable by IDEAL-IQ instead of 1H-MRS. CONCLUSION: The findings of this study suggested that IDEAL-IQ may be useful as a noninvasive and objective method in the evaluation of patients with NPC; additionally, IDEAL-IQ can be used to quantitatively measure the brain parenchymal adipose content and monitor patient follow-up after treatment of NPC.
Brain ; Female ; Follow-Up Studies ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Magnetic Resonance Spectroscopy ; Male ; Methods ; Niemann-Pick Diseases ; Proton Magnetic Resonance Spectroscopy ; Water