OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

The development of chemoresistance which results in a poor prognosis often renders current treatments for colorectal cancer(CRC).In this study,we identified reduced microvessel density(MVD)and vascular immaturity resulting from endothelial apoptosis as therapeutic targets for overcoming chemoresistance.We focused on the effect of metformin on MVD,vascular maturity,and endothelial apoptosis of CRCs with a non-angiogenic phenotype,and further investigated its effect in overcoming chemoresistance.In situ transplanted cancer models were established to compare MVD,endothelial apoptosis and vascular maturity,and function in tumors from metformin-and vehicle-treated mice.An in vitro co-culture system was used to observe the effects of metformin on tumor cell-induced endothelial apoptosis.Transcriptome sequencing was performed for genetic screening.Non-angiogenic CRC developed inde-pendently of angiogenesis and was characterized by vascular leakage,immaturity,reduced MVD,and non-hypoxia.This phenomenon had also been observed in human CRC.Furthermore,non-angiogenic CRCs showed a worse response to chemotherapeutic drugs in vivo than in vitro.By suppressing endo-thelial apoptosis,metformin sensitized non-angiogenic CRCs to chemo-drugs via elevation of MVD and improvement of vascular maturity.Further results showed that endothelial apoptosis was induced by tumor cells via activation of caspase signaling,which was abrogated by metformin administration.These findings provide pre-clinical evidence for the involvement of endothelial apoptosis and subsequent vascular immaturity in the chemoresistance of non-angiogenic CRC.By suppressing endothelial apoptosis,metformin restores vascular maturity and function and sensitizes CRC to chemotherapeutic drugs via a vascular mechanism.

Teprotumumab-trbw,a monoclonal antibody that acts on the insulin growth factor-Ⅰ receptor, was approved in 2020 for the treatment of thyroid-associated ophthalmopathy, but little is known about it in China. It is hoped to provide guidance for clinical use through the review of its molecular structure, pharmacokinetics, therapeutic mechanism, clinical research and safety. It inhibits immune inflammation by blocking thyroid-stimulating hormone receptor /insulin growth factor-Ⅰ receptor crosstalk signaling, so as to reduce the production of hyaluronic acid and inflammatory factors in response. It can also promote the apoptosis of retro-orbital fibroblasts/adipocytes and inhibit the expression of genes related to the synthesis of thyroid hormones, thereby significantly improving the clinical symptoms such as exophthalmos and diplopia. The common adverse reactions of Teprotumumab-trbw are muscle spasm, hyperglycemia, hearing loss and so on. Teprotumumab-trbw is effective and durable in the treatment of thyroid-associated ophthalmopathy, and patients with secondary treatment can also benefit from it, which provides a new way and hope for the treatment of thyroid-associated ophthalmopathy.

OBJECTIVE: To evaluate the efficacy and safety of Cidan Capsule combined with adjuvant transarterial chemoembolization (TACE) in patients with a high risk of early recurrence after curative resection of hepatocellular carcinoma (HCC). METHODS: A multicenter, randomized controlled trial was conducted in patients with high-risk recurrence factors after curative resection of HCC from 9 medical centers between July 2014 and July 2018. Totally 249 patients were randomly assigned to TACE with or without Cidan Capsule administration groups by stratified block in a 1:1 ratio. Postoperative adjuvant TACE was given 4-5 weeks after hepatic resection in both groups. Additionally, 125 patients in the TACE plus Cidan group were administrated Cidan Capsule (0.27 g/capsule, 5 capsules every time, 4 times a day) for 6 months with a 24-month follow-up. Primary endpoints included disease-free survival (DFS) and tumor recurrence rate (TRR). Secondary endpoint was overall survival (OS). Any drug-related adverse events (AEs) were observed and recorded. RESULTS: As the data cutoff in July 9th, 2018, the median DFS was not reached in the TACE plus Cidan group and 234.0 days in the TACE group (hazard ratio, 0.420, 95% confidence interval, 0.290-0.608; P<0.01). The 1- and 2-year TRR in the TACE plus Cidan and TACE groups were 31.5%, 37.1%, and 60.8%, 63.4%, respectively (P<0.01). Median OS was not reached in both groups. The 1- and 2-year OS rates in TACE plus Cidan and TACE groups were 98.4%, 98.4%, and 89.5%, 87.9%, respectively (P<0.05). The most common grade 3-4 AEs included fatigue, abdominal pain, lumbar pain, and nausea. One serious AE was reported in 1 patient in the TACE plus Cidan group, the death was due to retroperitoneal mass hemorrhage and hemorrhagic shock, and was not related to study drug. CONCLUSIONS Cidan Capsule in combination with TACE can reduce the incidence of early recurrence in HCC patients at high-risk of recurrence after radical hepatectomy and may be an appropriate option in postoperative anti-recurrence treatment. (Registration No. NCT02253511).

OBJECTIVE: To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats. METHODS: Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA. RESULTS: The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05). CONCLUSION Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Animals ; Apoptosis ; Apoptosis Regulatory Proteins/metabolism* ; Autophagy ; Beclin-1 ; Caspase 3/metabolism* ; Cerebral Hemorrhage/therapy* ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Rats ; Rats, Sprague-Dawley ; bcl-2-Associated X Protein/metabolism*

Thyroid-associated ophthalmopathy(TAO)is an organ-specific autoimmune disease, which will cause a series of symptoms to significantly reduce the health level and life quality of patients. The pathogenesis of TAO has not been fully clarified. At present, there is a lack of unified and mature treatment scheme of it. Indeed, T-helper 17 lymphocyte(Th17)cells, regulatory T(Treg)cells and their imbalance are closely related to the immunological pathogenesis of TAO. It is currently believed that the cytokines secreted by Th17 cells can not only promote the inflammatory response of TAO and the fibrosis of orbital connective tissue, but also inhibit the adipogenic differentiation of TAO orbital connective tissue. In addition, Treg cells mainly exert immunosuppressive effect on TAO and delay the disease progression. At the same time, there is a dynamic balance relationship between Th17 and Treg cells, the imbalance of Th17/Treg cells can trigger the occurrence and development of TAO. This paper mainly expounds the influence mechanism of Th17, Treg cells and their balance on TAO, and analyzes the reasons for the differences between different research results, so as to provide some reference for the study of the pathogenesis and clinical treatment of TAO.

Objective:To explore the influencing factors of bowel preparation quality in hospitalized elderly patients, and to find the appropriate waiting time from the end of bowel preparation to the beginning of colonoscopy.Methods:Baseline and clinical data of elderly patients over 60 years old who underwent colonoscopy in the Tenth People′s Hospital, Tongji University from February 2021 to August 2021 were collected. Multivariate analysis was used to screen the factors that might affect the quality of bowel preparation in hospitalized elderly patients. Patients were grouped according to waiting time before colonoscopy. After eliminating confounding factors using propensity matching analysis, the difference of bowel preparation quality among groups was compared.Results:251 patients were included in the study. Multivariate analysis revealed that, hypertension ( OR=3.530, 95% CI 1.295-9.618), chronic constipation ( OR=3.302,95% CI 1.132-9.632), dietary compliance ( OR=0.161, 95% CI 0.070-0.371), medication and drinking water compliance ( OR=0.167, 95% CI 0.070-0.397), exercise compliance after medication ( OR=2.245, 95% CI 1.040-4.845), The frequency of defecation after medication ( OR=0.446, 95% CI 0.308-0.647) and waiting time ( OR=0.537, 95% CI 0.387-0.745) were important factors affecting the quality of bowel preparation in hospitalized elderly patients ( P<0.05). There were differences in bowel preparation quality between groups of waiting times. The overall quality of bowel preparation in 120-180 min group was significantly better than that in 241-300 min group, 301-360 min group and>360 min group ( P<0.05). The overall quality of bowel preparation in 181-240 min group was better than that in >360 min group ( P<0.05). There were no significant differences among other groups( P>0.05). The scores of cecum and ascending colon were the best in 120-180 min group, and the cleanliness of descending colon, sigmoid colon and rectum was significantly higher in 241-300 min group, 301-360 min group and > 360 min group. The scores of descending colon, sigmoid colon and rectum showed that the intestinal preparation quality of 181-240 min group was better than that of 301-360 min group and > 360 min group. Conclusions:The best examination time for elderly patients is about 180 minutes after bowelpreparation. Medical workers should flexibly guide the medication time to ensure that patients are in the best clean state of intestinal tract during examination.

OBJECTIVE: To compare the therapeutic effect between rehabilitation robot rehabilitation training synchronizing acupuncture exercise therapy and simple acupuncture exercise therapy on lower limb function and life activity ability for postoperative patients with hip fracture. METHODS: A total of 50 elderly postoperative patients with hip fracture were randomly divided into an observation group and a control group, 25 cases in each group. Both groups were treated with acupuncture at hip three points of the affected side and lateral line 1 of vertex, anterior oblique parietotemporal line of the healthy side, hip three needles were retained for 30 min. The scalp acupuncture needles were continue retained, the observation group was given acupuncture exercise therapy to synchronize lower limb rehabilitation robot rehabilitation training, and the control group was given acupuncture exercise therapy. The two groups were treated once a day, 7 times as a course of treatment, and totally 4 courses were required. The Harris score, Barthel index score and quadriceps femoris isokinetic muscle strength indexes [peak torque (PT), average power (AP), flexor peak torque/extensor peak torque (F/E)] were compared between the two groups before and after treatment. RESULTS: After treatment, the Harris score, Barthel index score, PT and AP were higher than those before treatment ( CONCLUSION Rehabilitation robot rehabilitation training of lower limbs synchronizing acupuncture exercise therapy could enhance the hip joint activity function and quadriceps muscle group function of elderly postoperative patients with hip fracture, and effectively improve the lower limb function and life activity ability.
Acupuncture Points ; Acupuncture Therapy ; Aged ; Exercise Therapy ; Humans ; Robotics ; Stroke ; Stroke Rehabilitation ; Treatment Outcome

Objective: As an important food therapy product with traditional Chinese medicine (TCM) applications, donkey-hide gelatin (Asini Corii Colla, ACC) has been used for thousands of years. However, till now few effective strategy had been proposed to distinguish ACC from other animal hide gelatins, especially closely related horse- and mule-hide gelatins, which was an embarrassment of ACC quality control. Methods: Combined mass spectrometry and bioinformatic methods have been applied to identify and verify two ACC-specific peptides (Pep-1 and Pep-2) capable of distinguishing ACC from other closely related animal gelatins with high selectivity. Results: It confirmed that these two peptides could be not only used for distinguishing ACC from highly homologous horse-hide and mule-hide gelatins as well as other animal hide gelatins. Conclusion: The present study provides a simple method for species-specific peptides discovery, which can be used for assessing the quality of animal gelatin products, and ensure they are authenticable and traceable.

BACKGROUND: Radical nephrectomy and thrombectomy is the standard surgical procedure for the treatment of renal cell carcinoma (RCC) with tumor thrombus (TT). But the estimation of intra-operative blood loss is only based on the surgeon's experience. Therefore, our study aimed to develop Peking University Third Hospital score (PKUTH score) for the prediction of intra-operative blood loss volume in radical nephrectomy and thrombectomy. METHODS: The clinical data of 153 cases of renal mass with renal vein (RV) or inferior vena cava tumor thrombus admitted to Department of Urology, Peking University Third Hospital from January 2015 to May 2018 were retrospectively analyzed. The total amount of blood loss during operation is equal to the amount of blood sucked out by the aspirator plus the amount of blood in the blood-soaked gauze. Univariate linear analysis was used to analyze risk factors for intra-operative blood loss, then significant factors were included in subsequent multivariable linear regression analysis. RESULTS: The final multivariable model included the following three factors: open operative approach (P < 0.001), Neves classification IV (P < 0.001), inferior vena cava resection (P = 0.001). The PKUTH score (0-3) was calculated according to the number of aforementioned risk factors. A significant increase of blood loss was noticed along with higher risk score. The estimated median blood loss from PKUTH score 0 to 3 was 280 mL (interquartile range [IQR] 100-600 mL), 1250 mL (IQR 575-2700 mL), 2000 mL (IQR 1250-2900 mL), and 5000 mL (IQR 4250-8000 mL), respectively. Meanwhile, the higher PKUTH score was, the more chance of post-operative complications (P = 0.004) occurred. A tendency but not significant overall survival difference was found between PKUTH risk score 0 vs. 1 to 3 (P = 0.098). CONCLUSION We present a structured and quantitative scoring system, PKUTH score, to predict intra-operative blood loss volume in radical nephrectomy and thrombectomy.