Study on blood pressure rhythm in hypertensive patients withdeficiency syndrome and a random forest model for predicting hypertension withdeficiency syndrome.

OBJECTIVE: To investigate blood pressure rhythm (BPR) in Yin deficiency syndrome of hypertension (YDSH) patients and develop a random forest model for predicting YDSH. METHODS: Our study was consistent with technical processes and specification for developing guidelines of Evidence-based Chinese medicine clinical practice (T/CACM 1032-2017). We enrolled 234 patients who had been diagnosed with primary hypertension without antihypertensive medications prior to the enrollment. All participants were divided into Yin deficiency group (YX, n = 74) and non-Yin deficiency group (NYX, n = 160). Participants were professionally grouped by three experienced chief Traditional Chinese Medicine (TCM) physicians according to four examinations (i.e., inspection, listening and smelling, inquiry and palpation). We collected data on 24 h ambulatory blood pressure monitoring (ABPM) and YDSH rating scale. We divided 24 h of a day into 12 two-hour periods [Chen-Shi (7:00-9:00), Si-Shi (9:00-11:00), Wu-Shi (11:00-13:00), Wei-Shi (13:00-15:00), Shen-Shi (15:00-17:00), You-Shi (17:00-19:00), Xu-Shi (19:00-21:00), Hai-Shi (21:00-23:00), Zi-Shi (23:00-1:00), Chou-Shi (1:00-3:00), Yin-Shi (3:00-5:00), Mao-Shi (5:00-7:00)] according to the theory of "midnight-midday ebb flow". We used random forest to build the diagnostic model of YDSH, with whether it was Yin deficiency syndrome as the outcome. RESULTS: Compared with NYX group, YX group had more female participants with older age, lower waist circumference, body mass index (BMI), diastolic blood pressure (DBP), and smoking and drinking rate (all P ＜ 0.05). The YDSH rating scores of YX group [28.5 (21.0-36.0)] were significantly higher than NYX group [13.0 (8.0-22.0)] (P < 0.001), and the typical symptoms of YX group included vexing heat in the chest, palms and soles, dizziness, dry eyes, string-like and fine pulse, soreness and weakness of lumbus and knees, palpitations, reddened cheeks, and tinnitus (all P < 0.05). The ratio of non-dipper hypertension in YX group was higher than in NYX group (56.9% vs 44.4%, P = 0.004). Compared with NYX group, 24 h DBP standard deviation (SD), nighttime DBP SD, Si-Shi DBP, Si-Shi mean arterial pressure (MAP), Hi-Shi systolic blood pressure (SBP), Hi-Shi DBP, Hi-Shi MAP, Zi-Shi SBP, Zi-Shi DBP, Zi-Shi MAP, Chou-Shi SBP SD, Chou-Shi DBP SD, Chou-Shi SBP coefficient of variation (CV) were lower in YX group (all P ＜ 0.05). Binary Logistic Regression analysis showed that the diagnosis of YDSH was positively correlated with age, heart rate, YDSH rating scores, and four TCM symptoms including vexing heat in the chest, palms and soles, string-like and fine pulse, soreness and weakness of lumbus and knees, and reddened cheeks (all P ＜ 0.05), but was negatively correlated with smoking (P﹥0.05). In addition, the diagnosis of YDSH was positively correlated with daytime SBP SD, nighttime SBP SD, nighttime SBP CV, and Hi-Shi SBP CV, but was negatively correlated with 24 h SBP CV, daytime DBP SD, nighttime DBP SD, and Hi-Shi DBP (all P ＜ 0.05). Hi-Shi SBP CV had independent and positive correlation with the diagnosis of YDSH after adjusting the variables of age, gender, course of hypertension, BMI, waist circumference, SBP, DBP, heart rate, smoking and drinking (P = 0.029). Diagnostic model of YDSH was established and verified based on the random forest. The results showed that the calculation accuracy, specificity and sensitivity were 77.3%, 77.8% and 76.9%, respectively. CONCLUSION: The BPR was significantly attenuated in YDSH patients, including lower 24 h DBP SD and nighttime DBP SD, and Hi-Shi SBP CV is independently correlated with the diagnosis of YDSH. The prediction accuracy of diagnosis model of YDSH based on the random forest was good, which could be valuable for clinicians to differentiate YDSH and non-Yin deficiency patients for more effective hypertensive treatment of TCM.

Acupotomy ameliorates subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis by regulating bone morphogenetic protein 2-Smad1 pathway.

OBJECTIVE: To investigate the effects of acupotomy on the subchondral bone absorption and mechanical properties in rabbits with knee osteoarthritis (KOA). METHODS: The rabbits were divided into blank control, model, acupotomy and electroacupuncture (EA) groups, with 12 rabbits in each. Modified Videman's method was used to prepare KOA model. The acupotomy and EA group were given indicated intervention for 3 weeks. The behavior of rabbits in each group was recorded. Subsequently, cartilage-subchondral bone units were obtained and morphological changes were observed by optical microscope and micro computed tomography. Compression test was used to detect the mechanical properties of subchondral bone, Western blot and real-time polymerase chain reaction (RT-PCR) were applied to detect the expression of bone morphogenetic protein 2-Smad1 (BMP2-Smad1) pathway in subchondral bone. RESULTS: Compared with the control group, rabbits in the KOA group showed lameness, knee pain, and cartilage degradation; the subchondral bone showed active resorption, the mechanical properties decreased significantly and the BMP2-Smad1 pathway downregulated significantly. Both acupotomy and EA intervention could increase the thickness of trabecular bone (Tb. Th), the bone volume fraction (BV/TV) and the thickness of subchondral bone plate, reduce the separation of trabecular bone (Tb. Sp), improve the maximum load and elastic modulus of subchondral bone, and effectively delay cartilage degeneration in KOA rabbits. This process may be achieved through upregulation the related proteins of BMP2-Smad1 pathway. The maximum load and elastic modulus of subchondral bone in the acupotomy group were slightly better than those in the EA group. CONCLUSIONS: Acupotomy could effectively protect cartilage by inhibiting abnormal bone resorption and improving mechanical properties of subchondral bone thorough the related proteins of BMP2-Smad1 pathway in KOA rabbits.

Evaluation of PAP in EGFR Mutational Testing in Advanced NSCLC: a Comparative Study.

BACKGROUND: EGFR mutational testing is crucial for advanced non-squamous NSCLC. PAP is a sensitive and selective method to detect rare mutations. METHODS: Eighty-five patients with non-squamous NSCLC were enrolled in this study. A set of paired plasma samples from each patient were collected and detected by PAP and ARMS. RESULTS: Of 85 paired samples, 78.8% (67/85) presented the same mutational status by the two methods. There was no statistically significant difference between the mutation frequencies in plasma samples detected with PAP and ARMS (p = 0.096). CONCLUSIONS: PAP technology appears to be an alternative choice with relatively high sensitivity for the detection of plasma EGFR mutations.

EGFR exon 20 insertion mutation in advanced thymic squamous cell carcinoma: Response to apatinib and clinical outcomes.

Thymic carcinoma (TC) is a rare malignant tumor of the mediastinum with occult onset, rapid development, and poor prognosis. Surgery is the main treatment for early TC, but the majority of patients are diagnosed at Masaoka-Koga stage III or IV with local invasion or distant metastasis. Platinum and anthracyclines are currently considered key components of first-line chemotherapy for advanced TC; however, there are no standard treatment plans for patients who are refractory to first-line and further chemotherapy. The clinical effect is also unsatisfactory. Apatinib has been successfully applied as third-line treatment for advanced gastric cancer and has shown high efficacy in the treatment of various cancers, such as lung, liver, and colorectal cancers. Herein we report a case of advanced thymic squamous cell carcinoma harboring EGFR exon 20 insertion in which apatinib was administered after multi-line chemotherapy and radiotherapy and a partial response was achieved after five months of treatment. To date, a five month overall response and 10 months of progression-free survival have been achieved. Adverse reactions can be controlled and the patient's quality of life has improved. Apatinib provides a new option for clinicians to treat patients with advanced TC.