[A new cucurbitane glycoside from Picrorhiza scrophulariiflora].

Chemical constituents from the ethanol extract of Picrorhiza scrophulariiflora were isolated and purified by column chromatography. Their structures were identified by HR-MS, 1D and 2D-NMR, and their cytotoxicity was assessed by CCK-8 assay. Four compounds were isolated and identified as follows: 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosterol-5,25-diene-22-one(1), 2ß-D-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,24-diene-22-one(2), 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5-ene-22-one(3) and 25-acetoxy-2ß-glucosyloxy-3ß,16α,20ß-trihydroxy-9-methyl-19-norlanosta-5,23-(E)-diene-22-one(4). Compound 1 represents a new cucurbitane glycoside. The half inhibitory concentrations of the 4 compounds exceeded 100 µmol·L~(-1) against four tumor cell lines, indicating no significant cytotoxicity.

Longitudinal change in end-digit preference in blood pressure recordings in the hypertension patients followed up in primary care clinics.

SUBJECT: This study was to evaluate whether a special lecture on the Chinese Guideline for Blood Pressure Measurement (CGBPM) improves end-digit preference (EDP) of blood pressure (BP) recordings in primary care clinics. METHODS: In 2012, the doctors working in a clinic received a lecture, which emphasizes that when mercurial sphygmomanometer was used, only 0, and even numbers could be recorded as BP end-digit. In 2016, we collected the BP recordings (2011-2015) of 462 hypertensive patients followed in the educated clinic or in another no-educated clinic. The percentages of 0, 2, 4, 6, 8 in BP end-digit were calculated for evaluating zero EDP, and the percent decline in each year was calculated on the formula: (baseline percentage - actual percentage in a year)/baseline percentage. RESULTS: In 2011, the percentage of zero end-digit was over 75% for SBP or DBP in both clinics. Against the no-educated clinic, the educated clinic had significant higher percent decline of zero EDP on SBP (31.5% vs -2.6%) and DBP (36.9% vs -14.3%) in 2013, and in 2014 (SBP 38.0% vs 11.6%; DBP 42.8% vs -4.0%). In 2015, the educated clinic still had higher percent decline of zero EDP on DBP (43.3% vs 29.3%). Furthermore, the percentages of zero end-digit for SBP (43.6% vs 49.2%) or for DBP (43.5% vs 59.0%) were lower in the educated clinic in 2015. CONCLUSION: Education on BP measurement and recording could improve the quality of BP recordings, and this effect may last for three years.

An Inflammation-Related Nine-Gene Signature to Improve Prognosis Prediction of Lung Adenocarcinoma.

BACKGROUND: A novel predictive model was rarely reported based on inflammation-related genes to explore clinical outcomes of lung adenocarcinoma (LUAD) patients. METHODS: Using TCGA database, we screened nine inflammation-related genes with a prognostic value, and LASSO regression was applied for model construction. The predictive value of the prognostic signature developed from inflammation-related genes was assessed by survival assays and multivariate assays. PCA and t-SNE analysis were performed to demonstrate clustering abilities of risk scores. RESULTS: Thirteen inflammation-related genes (BTG2, CCL20, CD69, DCBLD2, GPC3, IL7R, LAMP3, MMP14, NMUR1, PCDH7, PIK3R5, RNF144B, and TPBG) with prognostic values were finally identified. LASSO regression further screened nine candidates (BTG2, CCL20, CD69, IL7R, MMP14, NMUR1, PCDH7, RNF144B, and TPBG). Then, a prognostic prediction model using the above nine genes was constructed. A reliable clustering ability of risk score was demonstrated by PCA and t-SNE assays in 500 LUAD patients. The survival assays revealed that the overall survivals of the high-risk group were distinctly poorer than those of the low-risk group with 1-, 3-, and 5-year AUC values of 0.695, 0.666, and 0.694, respectively. Finally, multivariate assays demonstrated the scoring system as an independent prognostic factor for overall survival. CONCLUSIONS: Our study shows that the signature of nine inflammation-related genes can be used as a prognostic marker for LUAD.

Buzhong Tiaogan Formula for delaying colorectal liver metastasis (liver depression spleen deficient type): A multicenter randomized controlled trial: A study protocol.

INTRODUCTION: Colorectal cancer has been ranked third among the most common cancers worldwide and raised to the second leading cause of cancer death with nearly one-tenth of cancer-related deaths globally, and nearly half of colorectal cancer patients present with or develop colorectal cancer liver metastasis (CRLM). Buzhong Tiaogan Formula (BTF) has been proven to treat CRLM in our team, but there are lacking of evidence on its effective in delaying colorectal liver metastasis (liver depression spleen deficiency type), so we will evaluate the efficacy and safety of BTF in preventing the occurrence of CRLM. METHODS: This randomized controlled trial (RCT) will be carried out in 3 different hospitals in Shanxi Province planning to recruit 150 CRLM patients with the type of liver depression spleen deficiency. The control group will be treated by basic antitumor therapy and the treatment group will use BTF plus basic antitumor therapy. The primary outcomes will be quality of life of included patients, the time of occurrence of liver metastasis, the score of traditional Chinese medicine symptom for the type of liver depression spleen deficiency; and the secondary outcomes will include overall survival, progression-free survival, DFS, tumor microenvironment and immune state of the included patient. Safety evaluation will be recorded during the whole study. All data in this RCT will be analyzed by SPSS 23.0 software. This study has been approved by the Clinical Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06016). DISCUSSION: The results of this RCT will contribute to BTF for delaying colorectal liver metastasis (liver depression spleen deficient type). And the results from this RCT will be published in a relevant journal after finished. TRIAL REGISTRATION: ChiMCTR2100005268 (September 4, 2021).

The efficacy and safety of modified Gegenqinlian Fomular for advanced colorectal cancer (damp heat accumulation type): A multicenter randomized controlled trial.

INTRODUCTION: CRC, the incidence of the fourth highest among males and the third among females, is one of the malignant tumors that seriously threaten human health. The principle of treatment for advanced stage CRC is a multidisciplinary and comprehensive treatment based on chemotherapy, which always bring significant toxic side effects. CHM has advantages in the treatment of tumors with the effect on improving clinical symptoms and reducing side effects. GGQL formula is mainly used for treating abnormal defecates caused by damp-heat, so we will evaluate the clinical efficacy and safety of modified GGQL formula for patients with advanced CRC with the type of damp-heat in this study. METHODS: Multicenter RCT with two parallel groups in three hospitals planning to recruit 120 CRC patients with the type of damp-heat will be conducted. The control group will be treated by basic antitumor therapy and the treatment group will use modified GGQL formula plus basic antitumor therapy. The primary outcomes will be quality of life, TCM symptom score, PFS and OS, and the secondary outcomes will be performance status, size of tumor, tumor marker in the serum, tumor microenvironment and immune status. All analyses will be based on an intention-to-treat principle. This study was approved by the Human Research Ethics Committee of Shanxi Province Hospital of Traditional Chinese medicine (2021Y-06017). The results will be published in relevant journal. DISCUSSION: The results of this RCT will contribute to Chinese herbal medicine for treating CRC patients with the type of damp heat accumulation. TRIAL REGISTRATION: ChiCTR2100050754 (September 4, 2021).

Glycine protects against non-alcoholic hepatitis by downregulation of the TLR4 signaling pathway.

OBJECTIVE: To evaluate the effect of glycine on regulation of the hepatic toll-like receptor 4 (TLR4) signaling pathway by metabolic endotoxemia in a rat model of non-alcoholic steatohepatitis (NASH). METHODS: The NASH rat model was generated by feeding the animals a high-sucrose, high-fat for diet for 12 weeks. We then measured alterations in levels of LPS, TNFα, IL-6, ALT, TG in plasma, and TNFα, and IL-6 in liver. We performed hematoxylin and eosin (HE) staining and immunohistochemical staining to document pathological changes. Expression of TLR4 and IRS-1 in liver was measured by Western Blot and RT-PCR. RESULTS: Compared with control animals, levels of LPS, TNFα, IL-6 in plasma and the levels of TNFα, IL-6 in liver tissues gradually increased. Pathological changes and expression of TLR4 in liver were significantly increased compared with control. mRNA and protein levels of TLR4 and IRS-1 in livers were also upregulated. With concomitant treatment with glycine, endotoxin levels decreased, and TNFα and IL-6 levels in plasma and liver were significantly decreased compared to NASH rats. Pathological changes in liver and immunohistological expression of TLR4 in liver tissues were significantly improved compared to NASH rats. mRNA and protein levels of TLR4 were significantly downregulated while mRNA and protein levels of IRS-1 in liver were markedly upregulated. Progression of NASH appeared to be slowed or limited. CONCLUSION: These data suggest that hepatic TLR4 signaling pathway is activated in the NASH rat, and oral glycine may reduce the risk of endotoxemia and inflammation of the liver.

White coat effect in hypertensive patients: the role of hospital environment or physician presence.

This study was to evaluate the role of hospital environment or physician presence for white coat effect (WCE) in hypertensive patients. At first, 54 hypertensive outpatients diagnosed on office blood pressure (OBP) were included for 2-week placebo run in. During the second week of the run in period, home BP was measured using electronic BP monitors for 5-7 days. Finally, 26 sustained hypertensive patients with home systolic BP/diastolic BP over 135/85 (but <180/110) mm Hg were enrolled for 8-week treatment of nifedipine controlled-release tablet. In the visit day, BP was measured by patient-self (OBP-p) or by doctor (OBP-d) according to order determined with randomization method. The self-BP measurement was performed in a reception room of hospital. The differences between home BP and OBP-d or OBP-p were calculated as WCE calculated on doctor-measurement (WCE-d) or WCE calculated on patient-measurement (WCE-p), respectively. The home and OBP were measured with the same BP device for each patient during the study period. In the total 54 outpatients received placebo, the WCE-d was similar to the WCE-p (for systolic BP 6.6 ± 14.4 vs. 6.8 ± 15.8 mm Hg, NS; for diastolic BP 3.3 ± 8.8 vs. 2.9 ± 9.2 mm Hg, NS). Meanwhile, the 26 sustained hypertensive patients had similar systolic WCE-d and WCE-p (4.8 ± 10.3 vs. 5.0 ± 12.2 mm Hg, NS) at placebo stage. Similarly, these values were comparable (3.0 ± 14.0 vs. 2.2 ± 14.4 mm Hg, NS) in treatment stage. Hospital environment plays a main role for the WCE in hypertensive patients.

How to evaluate BP measurements using the oscillometric method in atrial fibrillation: the value of pulse rate variation.

An oscillometric device is recommended for blood pressure (BP) measurement in atrial fibrillation (AF), but there is still controversy concerning its accuracy. Therefore, evaluation of BP values in AF patients remains a challenge. This study included 251 patients with AF and 154 participants with sinus rhythm (SR). Pulse rate (PR) and BP were measured using an oscillometric device three times. The differences between the highest and lowest PR and the systolic and diastolic BP (SBP and DBP) were calculated as ΔPR, ΔSBP and ΔDBP, respectively. AF patients were stratified with respect to ΔPR in 0-5, 6-10, 11-15 and >15 subgroups. The AF group had a greater ΔPR (12.1±8.6 vs. 4.10±3.21 b.p.m., P<0.001), ΔSBP and ΔDBP than the SR group at similar SBP and DBP. A positive correlation existed between ΔPR and ΔSBP (r=0.255, P<0.001) in AF patients, but no correlation was found in SR subjects. Meanwhile, the ΔSBP in the 0-5 and 6-10 subgroups (9.58±5.61 and 10.67±6.77 vs. 8.45±5.25 mm Hg, nonsignificant) was similar to the SR group, whereas ΔSBP in the 11-15 and >15 subgroups was significantly greater than the SR group. Regardless of ΔPR, the ΔDBP in the AF group was significantly greater than that of the SR group. The AF patients who exhibited greater variability in their PR also had a greater variability in their SBP readings. The SBP measurement for AF patients is accurate as the measurement for patients with SR if the ΔPR is of 0-10 b.p.m. in AF.

Is 10-second electrocardiogram recording enough for accurately estimating heart rate in atrial fibrillation.

BACKGROUND: At present, the estimation of rest heart rate (HR) in atrial fibrillation (AF) is obtained by apical auscultation for 1min or on the surface electrocardiogram (ECG) by multiplying the number of RR intervals on the 10second recording by six. But the reasonability of 10second ECG recording is controversial. METHODS: ECG was continuously recorded at rest for 60s to calculate the real rest HR (HR60s). Meanwhile, the first 10s and 30s ECG recordings were used for calculating HR10s (sixfold) and HR30s (twofold). The differences of HR10s or HR30s with the HR60s were compared. The patients were divided into three sub-groups on the HR60s <80, 80-100 and >100bpm. RESULTS: No significant difference among the mean HR10s, HR30s and HR60s was found. A positive correlation existed between HR10s and HR60s or HR30s and HR60s. Bland-Altman plot showed that the 95% reference limits were high as -11.0 to 16.0bpm for HR10s, but for HR30s these values were only -4.5 to 5.2bpm. Among the three subgroups with HR60s <80, 80-100 and >100bpm, the 95% reference limits with HR60s were -8.9 to 10.6, -10.5 to 14.0 and -11.3 to 21.7bpm for HR10s, but these values were -3.9 to 4.3, -4.1 to 4.6 and -5.3 to 6.7bpm for HR30s. CONCLUSION: As 10s ECG recording could not provide clinically accepted estimation HR, ECG should be recorded at least for 30s in the patients with AF. It is better to record ECG for 60s when the HR is rapid.

How to estimate heart rate from pulse rate reported by oscillometric method in atrial fibrillation: The value of pulse rate variation.

OBJECTIVES: To evaluate whether the mean pulse rate (PR) from three oscillometric blood pressure (BP) measurements provides an accurate estimation of electrocardiogram ventricular rate (HR) in patients with permanent atrial fibrillation (AF). METHODS: BP and PR were measured with an oscillometric BP device for three times with one-minute interval. Simultaneously, one-minute electrocardiogram was also recorded for three times. The first PR and HR values were recorded as PR1 and HR1, and the averages of three PR and HR values as mean PR (mPR) and mean HR (mHR). Meanwhile, the differences between the highest and lowest values among the three PR and HR were calculated as ΔPR and ΔHR. Furthermore, the patients were stratified on ΔPR into the 0-15 and >15 subgroups. RESULTS: A moderate positive correlation existed between PR1 and HR1 or mPR and mHR, and Bland-Altman plot also showed quite wide 95% limits between them. Meanwhile, ΔPR was significantly higher than ΔHR (12.1±8.6 vs 3.6±2.5bpm, P<0.001). However, in the 0-15 subgroup, the correlation between mPR and mHR was high (R2=0.800), and the 95% limits were only from -11.3 to 14.2bpm with a difference of 1.4bpm. The coincidence (mPR-mHR<10bpm) rate was 93.9% when PR≤80bpm, 96.3% when PR 81-100bpm, and 88.9% when PR over 100bpm. CONCLUSION: The average of three PR values reported by an oscillometric BP device could provide a clinically accepted estimation of mean HR of 3min in AF patients with ΔPR 0-15bpm and mean PR ≤100bpm.