Effects of esophageal squamous cell carcinoma-related long non-coding RNA ESCCAL-1 on polarization of macrophages / 肿瘤研究与临床

Objective:To explore the effect of esophageal squamous cell carcinoma-related long non-coding RNA (lncRNA) ESCCAL-1 on the polarization of THP-1 cells-derived macrophages.Methods:The esophageal cancer cell line KYSE450 was divided into 5 groups: KYSE450 group (normal KYSE450 cells), shRNA-ESCCAL-1 group (infected with knockout ESCCAL-1 lentivirus), shRNA-NC group (infected with interference control lentivirus), OE-ESCCAL-1 group (infected with overexpressing ESCCAL-1 lentivirus) and OE-NC group (infected with overexpressed control lentivirus). The expression of ESCCAL-1 was detected by real-time quantitative polymerase chain reaction (qRT-PCR). After co-culture of cells in each group with THP-1 cells-derived macrophages, flow cytometry was used to detect the expressions of THP-1 cells-derived macrophages M1 polarization markers HLA-DR, iNOS, CD86 and M2 polarization markers Arg-1, CD163, CD206, and inflammatory cytokines.Results:After THP-1 cells were stimulated with 100 ng/ml phorbol ester for 48 hours, the cells grew adherently, and the expression levels of CD11b and CD36 increased, indicating that THP-1 cells were successfully differentiated into macrophages. After THP-1 cells-derived macrophages were co-cultured with esophageal cancer KYSE450 cell line treated differently for 24 hours, there were no significant differences in the expressions of M1 polarization markers HLA-DR, iNOS and CD86 between shRNA-ESCCAL-1 group and shRNA-NC group or between OE-ESCCAL-1 group and OE-NC group (all P > 0.05). Compared with shRNA-NC group, the expressions of M2 polarization markers Arg-1, CD163 and CD206 in shRNA-ESCCAL-1 group decreased [8.54±0.29 vs. 11.83±0.69, 12.0±0.3 vs. 24.5±0.8, 2.05±0.23 vs. 14.54±1.10], and the differences were statistically significant ( t values were 7.636, 27.38 and 19.31, all P < 0.01); compared with the OE-NC group, the expressions of M2 polarization marker Arg-1, CD163 and CD206 in OE-ESCCAL-1 group increased [32.60±1.14 vs. 14.20±0.20, 43.7±1.5 vs. 25.1±1.2, 35.8±0.7 vs. 13.6±0.6], and the differences were statistically significant ( t values were -27.58, -17.24 and -43.98, all P < 0.01). Compared with shRNA-NC group, the expression level of interferon-γ in shRNA-ESCCAL-1 group decreased [(6.3±1.5) pg/ml vs. (20.0±2.6) pg/ml, t = 7.75, P = 0.001]; compared with OE-NC group, the expression level of interleukin-1RA in OE-ESCCAL-1 group increased [(3 167±306) pg/ml vs. (467±176) pg/ml, t = -13.27, P < 0.01]. Conclusions:Esophageal squamous cell carcinoma-related lncRNA ESCCAL-1 can promote the M2 polarization of macrophages.

Clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis / 中华烧伤杂志

Objective: To investigate the clinical effects of en bloc resection and debridement combined with gluteus maximus muscle flap in the treatment of ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Methods: A retrospective observational study was conducted. From May 2018 to February 2020, 8 patients with pressure ulcers on the ischial tuberosity combined with chronic osteomyelitis who met the inclusion criteria were admitted to Fuyang Minsheng Hospital, including 5 males and 3 females, aged 38-69 years, with unilateral lesions in 6 patients and bilateral lesions in 2 patients. According to the anatomical classification of Cierny-Mader osteomyelitis, there were 6 patients (7 sides) with focal type, and 2 patients (3 sides) with diffuse type. The wound areas were 3 cm×2 cm to 12 cm×9 cm on admission. The pressure ulcer and chronic osteomyelitis lesions were completely removed by en bloc resection and debridement. The chronic infectious lesions were transformed into sterile incisions like fresh wounds by one surgical procedure, and the gluteus maximus muscle flaps with areas of 10 cm×6 cm to 15 cm×9 cm were excised to transfer and fill the ineffective cavity. The wounds of 5 patients were sutured directly, and the wounds of 3 patients were closed by local flap transfer. The intraoperative blood loss volume and blood transfusion, and length of hospital stay of patients were recorded. The incision healing and flap survival of patients were observed after operation. The recurrence of pressure ulcer and osteomyelitis, the appearance of the affected area, and the secondary dysfunction and deformity of the muscle flap donor site of patients were observed during followed up. Results: The intraoperative blood loss volume of the 8 patients was 220 to 900 (430±150) mL; 5 patients received intraoperative blood transfusion, of which 2 patients received 3 U suspended red blood cells and 3 patients received 2 U suspended red blood cells. The length of hospital stay was 18 to 29 (23.5±2.0) d for the 8 patients. In this group of patients, the incisions of 7 patients healed, while in one case, the incision suture was torn off during turning over and healed after secondary suture. The flaps survived well in 3 patients who underwent local flap transfer. During the follow-up period of 6-20 months, no recurrence of pressure ulcer or osteomyelitis occurred in 8 patients, the affected part had skin with good texture, mild pigmentation, and no sinus tract formation, and no secondary dysfunction or deformity occurred in the donor site. Conclusions: The en bloc resection and debridement combined with gluteus maximus muscle flap has good clinical effects on ischial tubercle pressure ulcer complicated with chronic osteomyelitis. Neither pressure ulcer nor osteomyelitis recurs post operation. The skin texture and appearance of the affected area are good, and the donor site has no secondary dysfunction or deformity.

Clinical characteristics and outcomes of 111 neonates with upper airway obstruction admitted via transportation / 中华儿科杂志

Objectives: To analyze the clinical characteristics and outcomes of neonates with upper airway obstruction (UAO) who were admitted via transportation, hence to provide more evidence-based information for the clinical management of UAO. Methods: This was a single center retrospective study. Patients were hospitalized in Beijing Children's Hospital from January 1, 2016 to May 31, 2021 with age <28 days or postmenstrual age (PMA) ≤44 weeks, and UAO as the first diagnosis. The general information of patients, obstructed sites in the upper airway, treatment, complications and prognosis were analyzed. The outcomes of surgical UAO vs. non-surgical UAO were analyzed by 2 by 2 χ2 test. Results: A total of 111 cases were analyzed (2.3% of the total NICU hospitalized 4 826 infants in the same period), in which 62 (55.9%) were boys and 101 (91.0%) were term infants, and their gestational age was (38.7±2.0) weeks, birth weight (3 207±585) g, PMA on admission (40.8±2.5) weeks and weight on admission was (3 221±478) g. There were 92 cases (82.9%) with symptoms of UAO presenting on postnatal day 1, and 35 cases (31.5%) had extra-uterine growth retardation on admission. The diagnosis of UAO and the obstructive site was confirmed in 25 cases (22.5%) before transportation. There were 24 cases (21.6%), 71 cases (64.0%), and 16 cases (14.4%) who had UAO due to nasal, throat, and neck problems, respectively. The top 5 diagnosis of UAO were vocal cord paralysis (28 cases), bilateral choanal atresia (20 cases), laryngomalacia (15 cases), pharynx and larynx cysts (7 cases), and subglottic hemangioma (6 cases). The diagnosis and treatment of all the patients followed a multidisciplinary approach consisted of neonatal intensive care unit, ear-nose-throat department and medical image departments. A total of 102 cases (91.9%) underwent both bronchofiberscope and fiber nasopharyngoscope investigation. Seventy cases (63.1%) required ventilation. Among the 58 cases (52.3%) who required surgical intervention, 16 had tracheotomy. For cases with vs. without surgical intervention, the rate of cure and (or) improvement were 94.8% (55/58) vs. 54.7% (29/53), and the rate of being discharged against medical arrangement were 1.7% (1/58) vs. 45.3% (24/53) (χ²=24.21 and 30.11, both P<0.01). Conclusions: Neonatal UAO may locate at various sites of the upper airway. The overall prognosis of neonatal UAO is favorable. A multidisciplinary approach is necessary for efficient evaluation and appropriate surgical intervention.

Investigation on status of dyslipidemia in Chinese females aged 35 years or above / 中华心血管病杂志

Objective: To investigate the prevalence, awareness, treatment and control status of dyslipidemia among females aged ≥35 years old across China. Methods: Participants were selected by stratified multistage random sampling method in the "Twelfth Five-Year Plan" National Science and Technology Support Project "Survey on the Prevalence of Important Cardiovascular Diseases and Key Technology Research in China" project. This study is a retrospective, cross-sectional study. A total of 17 418 females aged 35 years and over were included in the current study. The basic information such as age, medical history and menopause was collected by questionnaire. The blood lipid parameters were derived from clinical laboratory examinations. The prevalence of dyslipidemia and the rate of awareness, treatment, and control of dyslipidemia were analyzed in females aged 35 years and over. Results: The age of participants was (56.2±13.0) years old, and the prevalence of dyslipidemia was 33.1% (5 765/17 418). The prevalence rates of high total cholesterol, hypertriglyceridemia, low HDL-C and high LDL-C were 9.7% (1 695/17 418), 11.1% (1 925/17 418), 10.9% (1 889/17 418) and 7.3% (1 262/17 418), respectively. The prevalence of dyslipidemia increased with age and the prevalence of dyslipidemia in women who were not married, Han, menarche age>16 years, obesity, central obesity, alcohol consumption, diabetes, hypertension and family history of cardiovascular disease were higher than those without such characteristics (P<0.05). There were 10 432 (59.9%) menopausal females in this cohort and prevalence of dyslipidemia of these participants was 38.8% (4 048/10 432), which was higher than that of non-postmenopausal females (24.6%, 1 717/6 986) (P<0.05). The awareness rates, treatment rates and control rates of dyslipidemia were 33.9% (1 953/5 765), 15.1% (870/5 765) and 2.5% (143/5 765) respectively among females aged 35 years and over in China. Conclusion: The prevalence of dyslipidemia in Chinese females aged 35 years and over is high, and its awareness, treatment, and control rates need to be optimized.

Effects of conbercept on type 1 macular neovascularization with different types of pigment epithelial detachment in neovascular age-related macular degeneration / 中华眼底病杂志

Objective:To observe the efficacy of intravitreal injection of conbercept (IVC) in the treatment of type 1 macular neovascularization (MNV) with different types of pigment epithelial detachment (PED) in neovascular age-related macular degeneration (nAMD).Methods:A retrospective clinical study. From June 2018 to June 2021, 42 patients with 42 eyes of nAMD type 1 MNV patients with different types of PED diagnosed in the ophthalmological examination of the Department of Ophthalmology, General Hospital of Central Theater Command were included in the study. All eyes underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT). The OCT examination was performed with a 3D-OCT 2000 instrument from Topcon Company in Japan. The fovea was scanned, and the PED height (PEDH), PED area (PEDA), PED volume (PEDV), and central foveal thickness (CFT) were measured. According to the OCT image features of PED, the affected eyes were divided into serous PED (sPED), fibrovascular PED (fPED), and hemorrhagic PED (hPED), and were grouped accordingly. Among the 42 eyes, 16 (38.1%, 16/42), 14 (33.3%, 14/42), and 12 (28.6%, 12/42) eyes were in the sPED group, fPED group, and hPED group, respectively. All patients received IVC treatment once a month for 3 consecutive months, and then on-demand treatment after assessment. BCVA and OCT were re-examined 3, 6, and 12 months after treatment, and the changes of BCVA, PEDH, PEDA, PEDV, and CFT in the affected eyes before and after treatment were compared, and repeated measures analysis of variance was used for statistical analysis.Results:At 12 months after treatment, the PEDH, PEDA and PEDV of the affected eyes in the sPED group, fPED group and hPED group were significantly lower than those before treatment, and the difference was statistically significant ( P<0.05). The difference in the degree of improvement was -318.67±258.09 μm, -6.50±6.33 μm 2, -1.95±1.78 μm 3 in the hPED group; -119.31±224.13 μm, -0.86 ±5.00 μm 2, -0.56±1.64 μm 3 in the sPED group; fPED group were -53.93±92.51 μm, -0.76±2.54 μm 2, -0.19±0.46 μm 3. The improvement degree of the affected eyes in hPED group was significantly greater than that in sPED group and fPED group, and the difference was statistically significant ( F=5.918, 6.029, 5.494; P<0.05). Compared with the BCVA and CFT before treatment, 12 months after treatment, the difference was statistically significant in the fPED group and the hPED group ( P<0.05); there was no significant improvement in the sPED group ( P>0.05). There was no significant difference in the BCVA of the affected eyes in the three groups compared with those before treatment ( F=0.817, 0.741, 0.848; P>0.05). Conclusion:Conbercept can effectively improve or stabilize the visual function and anatomical morphology of eyes with type 1 MNV in nAMD with sPED, fPED and hPED, among which the anatomical effect is better for hPED.

Comparison of different loading doses followed by pro re nata regimens of intravitreal conbercept for diabetic macular edema / 中华眼底病杂志

Objective:To compare and observe the efficacy and safety of different administration methods of conbercept in the treatment of diabetic macular edema (DME).Methods:A retrospective clinical study. From November 2016 to November 2020, 135 eyes of 92 patients with foveal DME who were diagnosed in the Department of Ophthalmology of General Hospital of Central Theater Command received conbercept treatment were included in the study. All patients underwent best corrected visual acuity (BCVA) and optical coherence tomography (OCT) examinations. All the affected eyes received intravitreal injection of conbercept once a month for 3 months or 5 months, and then pro re nata (PRN) treatment based on the patient’s visual acuity and OCT examination results, namely 3+PRN or 5+PRN treatment plan, and divided into 3+PRN group (84 eyes) and 5+PRN group (51 eyes), respectively. There was no statistically significant difference in baseline information between the two groups of patients ( P>0.05). The changes of BCVA, centre retinal thickness (CRT), the number of intravitreal injections and the occurrence of complications in the two groups were compared and observed at the end of 12 months after treatment. The independent sample Mann-Whitney test was used to compare continuous variables between groups; the χ2 test was used to compare categorical variables. Results:At the end of 12 months after treatment, compared with baseline, the BCVA of 3+PRN group and 5+PRN group increased by 8.8±4.4, 9.2±6.1 letters, and CRT decreased by 145.1±50.5, 148.5±82.5 μm; there was no statistically significant difference between the two groups of eyes with BCVA increasing letter number and CRT decreasing value ( P=0.295, 0.548). In the 3+PRN group and 5+PRN group, the BCVA increased by more than 10 and 15 letters were 40 (47.6%, 40/84), 21 (25.0%, 21/84) eyes and 27 (52.9%, 27/51), 16 (31.4%, 16/51) eyes; there was no statistically significant difference in the proportion of the two groups with BCVA improvement> 10, 15 letters ( χ2=0.360, 0.648; P=0.549, 0.421). During PRN, in the eyes of 3+PRN group and 5+PRN group, the prognosis of eyesight was unstable in 22 (26.2%, 22/84) and 6 (11.8%, 6/51) eyes; the prognosis of eyes in the two groups was unstable. Compared with the number of eyes, the difference was statistically significant ( χ2=4.017, P=0.045). The number of injections into the vitreous cavity of the two groups of eyes were 4.1±2.9 and 2.4±1.8, the difference was statistically significant ( P<0.001); the times of remedial photocoagulation were 1.9±1.0, 1.5±0.8 times, the difference was statistically significant ( P=0.034). During the follow-up period, the overall incidence of ocular adverse events and serious adverse events in the 3+PRN group and 5+PRN group were similar, being 22.6% (19/84), 25.5% (13/51), and 8.3% (7/84), 7.8% (4/51), respectively. Conclusion:Both the 3+PRN and 5+PRN regimens of conbercept can treat DME safely and effectively; the 5+PRN regimen only requires fewer PRNs to maintain a more stable therapeutic effect.

Establishment of a rapid method for quality assessment of cardiotonic effect of Shengfupian / 药学学报

Based on the similar structure of adrenaline shared by higenamine (HI), salsolinol (SA) and coryneine (CO), a photochemical colorimetric sensor based on the displacement reaction of o-diphenol hydroxyl group and alizarin red S-phenylboric acid system was constructed to quickly distinguish and identify the cardiac strength of Shengfupian. The results show that the optimal condition of the sensor is: the molar ratio of alizarin red S (ARS) to phenylboric acid (PA) is 1∶3, reaction temperature is 0 ℃; The preparation method of the sample solution is optimized as follows: 2.5 g of Shengfupian powder was taken, 10 times the amount of methanol was added, and 300 W, 40 kHz ultrasound was carried out for 15 min; methodological studies showed that the method had good precision, repeatability and stability. The |△G| value (G is green, |△G| = |G after - G before|) of each sample was obtained by response values determination of 14 batches of Shengfupian. LC-MS/MS was used to determine the contents of three cardiac components in Shengfupian. It was found that the order of the total contents of cardiotonic components was basically consistent with |△G|. Then the correlation was analyzed, and the correlation coefficient R2 was as high as 0.87, which proved the scientificity and accuracy of this method. This study fills the methodological gap of rapid evaluation of the quality of Shengfupian, and provides the key technical support for the high quality and good price of Shengfupian in the market circulation and clinical application.

Value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight infants / 中国当代儿科杂志

OBJECTIVES@#To study the value of bedside echocardiography in predicting persistent patency of the ductus arteriosus during the early postnatal period in very low birth weight (VLBW) infants.@*METHODS@#A retrospective analysis was performed for 51 VLBW infants who were admitted from March 2020 to June 2021, with an age of ≤3 days and a length of hospital stay of ≥14 days. According to the diameter of patent ductus arteriosus (PDA) on days 14 and 28 after birth, the infants were divided into three groups: large PDA group (PDA diameter ≥2 mm), small PDA group (PDA diameter <2 mm), and PDA closure group (PDA diameter =0 mm). The echocardiographic parameters measured at 72 hours after birth were compared among the three groups. The receiver operating characteristic (ROC) curve was used to evaluate the value of the echocardiographic parameters in predicting persistent patency of the ductus arteriosus (PDA≥2 mm) at the ages of 14 and 28 days.@*RESULTS@#On day 14 after birth, there were 17 infants in the large PDA group, 11 in the small PDA group, and 23 in the PDA closure group. On day 28 after birth, there were 14 infants in the large PDA group, 9 in the small PDA group, and 26 in the PDA closure group. There were significant differences in gestational age, birth weight, rate of pulmonary surfactant use, and incidence rate of hypotension among the three groups (P<0.05). PDA diameter, end-diastolic velocity of the left pulmonary artery, left ventricular output, and left ventricular output/superior vena cava flow ratio measured at 72 hours after birth were associated with persistent patency of the ductus arteriosus at the ages of 14 and 28 days (P<0.05), and the ratio of the left atrium to aorta diameter was associated with persistent patency of the ductus arteriosus at the age of 28 days (P<0.05). The ROC curve analysis showed that the area under the curve that the PDA diameter measured at 72 hours after birth predicting the persistent patency of the ductus arteriosus at the ages of 14 and 28 days was the largest (0.841 and 0.927 respectively), followed by end-diastolic velocity of the left pulmonary artery, with the area under the curve of 0.793 and 0.833 respectively.@*CONCLUSIONS@#The indicators obtained by beside echocardiography at 72 hours after birth, especially PDA diameter and end-diastolic velocity of the left pulmonary artery, can predict persistent patency of the ductus arteriosus at the ages of 14 and 28 days in VLBW infants, which provides a basis for the implementation of early targeted treatment strategy for PDA.

Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease / 中国中药杂志

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Effect of duodenal stump reinforcement on postoperative complications in patients undergoing laparoscopic radical gastrectomy / 中华胃肠外科杂志

Objective: To evaluate the influence of duodenal stump reinforcing on the short-term complications after laparoscopic radical gastrectomy. Methods: A retrospective cohort study with propensity score matching (PSM) was conducted. Clinical data of 1204 patients with gastric cancer who underwent laparoscopic radical gastrectomy at the First Affiliated Hospital of Army Medical University from April 2009 to December 2018 were collected. The digestive tract reconstruction methods included Billroth II anastomosis, Roux-en-Y anastomosis and un-cut-Roux- en-Y anastomosis. A linear stapler was used to transected the stomach and the duodenum. Among 1204 patients, 838 were males and 366 were females with mean age of (57.0±16.0) years. Duodenal stump was reinforced in 792 cases (reinforcement group) and unreinforced in 412 cases (non-reinforcement group). There were significant differences in resection range and anastomotic methods between the two groups (both P<0.001). The two groups were matched by propensity score according to the ratio of 1∶1, and the reinforcement group was further divided into purse string group and non-purse string group. The primary outcome was short-term postoperative complications (within one month after operation). Complications with Clavien-Dindo grade ≥ III a were defined as severe complications, and the morbidity of complication between the reinforcement group and the non-reinforcement group, as well as between the purse string group and the non-purse string group was compared. Results: After PSM, 411 pairs were included in the reinforcement group and the non-reinforcement group, and there were no significant differences in baseline data between the two groups (all P>0.05). No perioperative death occurred in any patient.The short-term morbidity of postoperative complication was 7.4% (61/822), including 14 cases of anastomotic leakage (23.0%), 11 cases of abdominal hemorrhage (18.0%), 8 cases of duodenal stump leakage (13.1%), 2 cases of incision dehiscence (3.3%), 6 cases of incision infection (9.8%) and 20 cases of abdominal infection (32.8%). Short-term postoperative complications were found in 25 patients (6.1%) and 36 patients (8.8%) in the reinforcement group and the non-reinforcement group, respectively, without significant difference (χ2=2.142, P=0.143). Nineteen patients (2.3%) developed short-term severe complications (Clavien-Dindo grade ≥IIIa), while no significant difference in severe complications was found between the two groups (1.7% vs. 2.9%, χ2=1.347, P=0.246). Sub-group analysis showed that the morbidity of short-term postoperative complication of the purse string group was 2.6% (9/345), which was lower than 24.2% (16/66) of the non-purse string group (χ2=45.388, P<0.001). Conclusion: Conventional reinforcement of duodenal stump does not significantly reduce the incidence of duodenal stump leakage, so it is necessary to choose whether to reinforce the duodenal stump individually, and purse string suture should be the first choice when decided to reinforce.

NCTD Retards AML HL60 Cell Proliferation via Targeting Hedgehog/SOX2 axis / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of norcantharidin (NCTD) to proliferation of leukemia cells through disrupting key regulators of sonic Hedgehog (SHH) pathway and its downstream transcription factor SOX2.@*METHODS@#CCK8 was used to detected the HL60 and NB4 cells after inhibited by NCTD, SMO and GLI1 inhibitor for 24 hours. Expression level of SMO, GLI1 and SOX2 in HL60 cells with NCTD treatment was detected by immunoblot. HL60 cells were transfected with pcDNA3.1 plasmid expressing GLI1 or SOX2. Empty vector and pcDNA3. 1-EGFP were divided into negative and positive control group, respectively. The expression of exogenous GLI1 or SOX2 in HL60 cells was confirmed by immunoblot, and growth curve of HL60 cell was checked by CCK8. Proliferation of genetic modified HL60 cells treated by various dose of NCTD was detected.@*RESULTS@#NCTD, SMO/GLI1 inhibitors could inhibit the proliferation of NB4 and HL60 cells in a dose-dependent manner. Compared with solvent (DMSO)-treated control group, NCTD remarkably decreased protein level of SMO, GLI1 and SOX2. GLI1 and SOX2 were overexpressed in HL60 cells as compared with pcDNA3.1 empty vector-transfected group. Growth curve demonstrated significant proliferative advantage of GLI1/SOX2-transfected cells. CCK8 assay indicated that GLI1/SOX2-overexpressed HL60 cells were more resistant to NCTD treatment.@*CONCLUSION@#NCTD attenuates HL60 proliferation via targeting the Hedgehog/SOX2 axis.

Research advances in the role of ferroptosis in neonatal hypoxic-ischemic brain damage / 中国当代儿科杂志

Neonatal hypoxic-ischemic brain damage (HIBD) remains an important cause of neonatal death and disability in infants and young children, but it has a complex mechanism and lacks specific treatment methods. As a new type of programmed cell death, ferroptosis has gradually attracted more and more attention as a new therapeutic target. This article reviews the research advances in abnormal iron metabolism, glutamate antiporter dysfunction, and abnormal lipid peroxide regulation which are closely associated with ferroptosis and HIBD.

Mechanism of astragaloside Ⅳ alleviating PC12 cell injury by activating PI3K/AKT signaling pathway: based on network pharmacology and in vitro experiments / 中国中药杂志

In this study, the molecular mechanism of astragaloside Ⅳ(AS-Ⅳ) in the treatment of Parkinson's disease(PD) was explored based on network pharmacology, and the potential value of AS-Ⅳ in alleviating neuronal injury in PD by activating the PI3 K/AKT signaling pathway was verified through molecular docking and in vitro experiments. Such databases as SwissTargetPrediction, BTMAN-TAM, and GeneCards were used to predict the targets of AS-Ⅳ for the treatment of PD. The Search Tool for the Retrieval of Interacting Genes/Proteins(STRING) was employed to analyze protein-protein interaction(PPI) and construct a PPI network, and the Database for Annotation, Visualization and Integrated Discovery(DAVID) was used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. Based on the results of GO enrichment analysis and KEGG pathway analysis, the PI3 K/AKT signaling pathway was selected for further molecular docking and in vitro experiments in this study. The in vitro cell model of PD was established by MPP~+. The cell viability was measured by MTT assay and effect of AS-Ⅳ on the expression of the PI3 K/AKT signaling pathway-related genes and proteins by real-time polymerase chain reaction(RT-PCR) and Western blot. Network pharmacology revealed totally 122 targets of AS-Ⅳ for the treatment of PD, and GO enrichment analysis yielded 504 GO terms, most of which were biological processes and molecular functions. Totally 20 related signaling pathways were screened out by KEGG pathway analysis, including neuroactive ligand-receptor interaction, PI3 K/AKT signaling pathway, GABAergic synapse, and calcium signaling pathway. Molecular docking demonstrated high affinity of AS-Ⅳ to serine/threonine-protein kinases(AKT1, AKT2), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma(PIK3 CG), and phosphoinositide-3-kinase, catalytic, alpha polypeptide(PIK3 CA) on the PI3 K/AKT signaling pathway. In vitro experiments showed that AS-Ⅳ could effectively inhibit the decrease of the viability of PC12 induced by MPP~+ and up-regulate the mRNA expression levels of AKT1 and PI3 K as well as the phosphorylation levels of AKT and PI3 K. As an active component of Astragali Radix, AS-Ⅳ acts on PD through multiple targets and pathways. Furthermore, it inhibits neuronal apoptosis and protects neurons by activating the PI3 K/AKT signaling pathway, thereby providing reliable theoretical and experimental supports for the treatment of PD with AS-Ⅳ.

Clinical value of TDI combined with 2D-STI on evaluating the microcirculation dysfunction and left ventricular dysfunction in patients with non-obstructive coronary angina / 中华心血管病杂志

Objective: To explore the value of tissue Doppler imaging (TDI) combined with two-dimensional speckle tracking imaging (2D-STI) at rest on evaluating microcirculation dysfunction and left ventricular dysfunction in patients with angina and no obstructive coronary artery disease(ANOCA). Methods: This retrospective study recruited 78 ANOCA patients, who hospitalized in the People's Hospital of Liaoning Province from August 2019 to July 2021. These patients underwent conventional echocardiography examination, including TDI and 2D-STI, to evaluate the left ventricular dysfunction, and adenosine stress echocardiography (SE) to evaluate the coronary flow velocity reserve (CFVR). ANOCA patients were divided into coronary microcirculation dysfunction CMD group (CFVR<2) and control group (CFVR≥2) according to CFVR. Clinical data, routine echocardiographic parameters, TDI parameters including isovolumic contraction time (IVCT), isovolumic relaxation time (IVRT), ejection time (ET), and STI parameters including global longitudinal peak strain (GLS), time to peak (TTP); peak strain dispersion (PSD) were compared between the two groups. Binary logistic regression was used to analyze the risk factors of CMD and the predictive value of each parameter to construct a joint prediction model for the diagnosis of CMD in this patient cohort. Results: The mean age was (55.5±11.2) years, 43 (55%) patients were females in this patient cohort, 38 (49%) patienst were didvided into the CMD group and 40 (51%) into the control group. Age, prevalence of hypertension, diabetes, dyslipidemia, and smokers were significantly higher in the CMD group than in the control group (all P<0.05). Tei index was higher, IVCT and TTP were longer, PSD was higher, ET was shorter, and absolute GLS was lower in the CMD group than in the control group (all P<0.05). The results of logistic regression analysis showed that longer IVCT, higher Tei index, higher time to PSD and lower absolute GLS were the independent risk factors of CMD. The ROC curve revealed that the predicting efficacy on CMD was satisfactiory with the combined predictors: AUC=0.884, sensitivity of 82% and specificity of 80%. Conclusions: TDI combined with 2D-STI is associated with a good diagnostic value on the diagnosis of CMD and left ventricular dysfunction in patients with ANOCA, which provides a feasible non-invasive tool for the diagnosis of CMD and risk stratification of patients with ANOCA.

Screening of prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and its anti-rheumatoid arthritis effect in vivo / 中国药科大学学报

@#The objectives of the study were to screen prostaglandin E2 receptor 4 antagonist from active compounds of Baeckea frutescens L. and to explore its anti-rheumatoid arthritis effect.The HEK293T-EP4 cell antagonist screening model was established in vitro. Homogeneous time-resolved fluorescence (HTRF) technique was used to screen the active compounds of Baeckea frutescens L..SPF grade ICR male mice were randomly divided into control group, model group, methotrexate group, and Baeckea frutescens L.compound BF-2 (100, 50 and 25 mg/kg) groups. The collagen-induced arthritis (CIA) mouse model was established in vivo. The swelling volume of the toes of mice was measured, and the pathological examination was analyzed by staining with hematoxylin and eosin.SPF grade ICR mice, male, were randomly divided into control group, BF-2 (100, 50 and 25 mg/kg) group, and aspirin group.The acetic acid-induced body writhing test was observed.The EP4 in vitro antagonist screening model was successfully established.The preliminary screening results found that BF-2, BF-20, BF-11 and BF-12 had strong EP4 antagonistic activity [(102.11 ± 3.45)%, (90.31 ± 3.59)%, (75.72 ± 1.79)% and (76.84 ± 1.64)%], and BF-2 had the strongest antagonistic activity (IC50 = 0.99 ± 0.08 μg/mL).BF-2 could significantly inhibit the toe swelling of CIA mice, and relieve the degradation of articular cartilage matrix and inflammatory cell infiltration.At the same time, compared with the control group, the writhing times of the mice in each dose of BF-2 were significantly reduced.In this study, BF-2 of Baeckea frutescens L.was selected as an EP4 antagonist, which has potential anti-rheumatoid arthritis activity.

Systematic review and Meta-analysis on efficacy and safety of Gongxuening Capsules in treatment of abnormal vaginal bleeding after medical abortion / 中国中药杂志

To systematically evaluate the efficacy and safety of Gongxuening Capsules in the treatment of abnormal vaginal bleeding after medical abortion. CNKI, Wanfang, SinoMed, VIP, PubMed, Cochrane Library and EMbase databases were retrieved to comprehensively collect the clinical randomized controlled trials(RCTs) of Gongxuening Capsules for treatment of abnormal vaginal bleeding after medical abortion from the establishment of the databases to October 10, 2020. Literature screening, data extraction and quality evaluation were conducted independently by two system reviewers according to the inclusion and exclusion criteria. Cochrane Handbook bias risk assessment tool was used for the literature methodology quality evaluation, RevMan 5.3 software was used for Meta-analysis, and the evidence quality of outcomes was evaluated by the evidence quality grading system(GRADE). A total of 16 RCTs were inclu-ded. The results of Meta-analysis showed that as compared with the western medicine treatment alone, the addition of Gongxuening Capsules to the western medicine treatment can reduce the amount of vaginal bleeding(RR=1.23, 95%CI[1.19, 1.27], P<0.000 01), shorten vaginal bleeding time(RR_(≤15 d number of people)=1.39, 95%CI[1.31, 1.48], P<0.000 01; MD_(number ofdays)=-1.20, 95%CI[-1.66,-0.74],P<0.000 01). However, there was no obvious advantage in abortion effect(RR=1.02, 95%CI[0.99, 1.06], P=0.14) and menstrual recovery(MD=-0.35, 95%CI[-0.96, 0.25], P=0.25). The results of GRADE showed that the grading level was low for vaginal bleeding volume and vaginal bleeding time, and extremely low for abortion effect and mens-trual recovery. In terms of safety, 16 studies reported adverse events. Only one study showed no adverse events and the rest showed transient nausea, vomiting, stomach burning, upper abdominal discomfort and other gastrointestinal symptoms. The results show that the addition of Gongxuening Capsules to the application of western medicine in treatment of drug abortion can reduce the amount of vaginal bleeding and shorten vaginal bleeding time, but the abortion effect and menstrual recovery have no obvious advantages. The use of Gongxuening Capsules helps to achieve less adverse reactions and higher safety. Due to the small sample size of the included studies and many methodological quality problems, no conclusions with clinical guidance value can be obtained. Large sample-zise, high-qua-lity randomized controlled trials are still needed for further verification.

Mechanism of Sanhuang Decoction in alleviating dextran sulfate sodium induced ulcerative colitis in mice with Candida albicans colonization:based on high-throughput transcriptome sequencing / 中国中药杂志

This study explored the mechanism of Sanhuang Decoction(SHD) in treating dextran sulfate sodium(DSS)-induced ulcerative colitis(UC) in mice with Candida albicans(Ca) colonization via high-throughput transcriptome sequencing. Specifically, the animal model was established by oral administration of 3.0% DSS for 7 days followed by intragastrical administration of Ca suspension at 1.0 × 10~8 cells for 4 days and then the mice were treated with SHD enema for 7 days. Afterwards, the general signs were observed and the disease activity index(DAI) was recorded every day. After mice were sacrificed, colon length and colon mucosa damage index(CMDI) were determined and the histomorphology was observed with the HE staining method. The fungal loads of feces were detected with the plate method. Anti-saccharomyces cerevisiae antibody(ASCA) and β-1,3-glucan in serum, and TNF-α, IL-1β, and IL-6 in serum and colon were detected by ELISA. High-throughput RNA sequencing method was adopted to identify transcriptome of colon tissues from the control, model and SHD(15.0 g·kg~(-1)) groups. Differentially expressed genes(DEGs) among groups were screened and the GO and KEGG pathway enrichment analysis of the DEGs was performed. The expression levels of NLRP3, ASC, caspase-1, and IL-1β genes related to the NOD-like receptor signaling pathway which involved 9 DEGs, were examined by qRT-PCR and Western blot. The results demonstrated that SHD improved the general signs, decreased DAI and Ca loads of feaces, alleviated colon edema, erosion, and shortening, and lowered the content of β-1,3-glucan in serum and TNF-α, IL-1β, and IL-6 in serum and colon tissues of mice. Transcriptome sequencing revealed 383 DEGs between SHD and model groups, which were mainly involved in the biological processes of immune system, response to bacterium, and innate immune response. They were mainly enriched in the NOD-like signaling pathway, cytokine-cytokine interaction pathway, and retinol metabolism pathway. Moreover, SHD down-regulated the mRNA and protein levels of NLRP3, caspase-1, and IL-1β. In a word, SHD ameliorates DSS-induced UC in mice colonized with Ca, which probably relates to its regulation of NOD-like receptor signaling pathway.

Short-term efficacy of primary treatment and dressing change with aflibercept for exudative age-related macular degeneration / 中华眼底病杂志

Objective:To observe the short-term effects of intravitreal injection of aflibercept (IVA) for initial treatment and dressing change on exudative age-related macular degeneration (eAMD).Methods:A retrospective clinical study. From June 2018 to February 2021, forty-nine eAMD eyes of 38 patients who underwent IVA treatment in Department of Ophthalmology of Central Theater Command Hospital of People’s Liberation Army were included in the study. Among them, there were 24 males with 29 eyes and 14 females with 20 eyes; the average age was 66.82±8.71 years. All affected eyes were treated with IVA. The initial loading dose was 2.0 mg, which was injected once a month for 3 consecutive months, followed by monthly review and treatment as needed. Of the 49 eyes, 26 eyes were initially treated (initial treatment group), they were diagnosed within 3 months of the first onset and followed by IVA treatment, and no intraocular drugs and surgery were performed from the onset to the first diagnosis. Twenty-three eyes were treated with drug exchange therapy (dressing change group), they received intravitreal injection of ranibizumab and/or conbercept more than 4 times 6 months before the replacement therapy, during which there was persistent interlaminar cystoid edema and/or subretinal fluid (SRF) in the macular area and no improvement in pigment epithelial detachment (PED). Before IVA treatment, there were no statistically significant differences in the best corrected visual acuity (BCVA), foveal thickness (CMT), PED height (PEDH), and PED volume (PEDV) of the two groups of eyes before IVA treatment ( P>0.05). The same equipment and methods as before treatment were used for related examinations, and the changes of BCVA, CMT, PEDH, PEDV and complications of the two groups of eyes were recorded in 1, 3, and 6 months after treatment. The comparison of BCVA, CMT, PEDH, and PEDV between the two groups were used repeated measures analysis of variance. Results:Six months after treatment, the number of IVA injections in the eyes of the initial treatment group and dressing change group were 4.15±0.73 and 4.39±0.72 times, respectively, and the difference was not statistically significant ( t=-1.141, P=0.260). The BCVA, CMT, PEDH, and PEDV of the the initial treatment group ( F=5.345, 22.995, 6.764, 5.425) and the dressing change group ( F=12.519, 15.576, 8.843, 9.406) were significantly improved compared before treatment with 1, 3, and 6 months. All were statistically significant ( P<0.05). There was no significant difference in BCVA, CMT, PEDH, and PEDV between the initial treatment group and the dressing group at each time point after treatment ( F=1.741, 0.069, 0.876, 3.455; P>0.05). During the follow-up period, none of the affected eyes had complications such as persistent intraocular pressure increase, endophthalmitis, and retinal pigment epithelial tear. Conclusions:IVA can improve eyesight of patients with eAMD and reduce CMT, PEDH, and PEDV. The initial treatment and dressing change have the same effect.

Characteristics of nailfold capillaroscopy examination of systemic sclerosis and its value in assessing the development of SSc / 中华风湿病学杂志

Objective:To identify the characteristics of nailfold capillaroscopy (NFC) of systemic sclerosis (SSc) and investigate whether more severe peripheral microangiopathy at NFC were related to the development of SSc.Methods:① The study included 115 patients (60 cases with SSc and 55 patients with other connective tissue diseases). All patients were treated with neither prednisone nor immunosuppressive drugs within 3 months before enrollment. We collected the following data: age, disease duration, disease onset, mRSS, high-resolution chest tomography (HRCT), echocardiography, pulmonary function, nailfold capillaroscopy and routine laboratory assessments. ② All the NFC definitions were used for semi-quantitatively scoring and Cutolo's qualitative assessment. ③ The relationship between NFC changes and joint, visceral involvement and autoantibodies in SSc patients was analyzed. ④ T test, Rank sum test and chi-square test were applied to analyze data. Results:① According to Cutoloqualitative assessment of NFC, patients of SSc with active/late pattern ( n=52) were very common than other CTD ( n=21) ( Z=-3.853, P<0.01). ② According to semiquantitative assessment, the scores of loss of capillaries [(1.67±0.60) vs (0.72±0.46), t=8.347, P<0.01)], irregular enlarged capillaries [(1.22±0.88) vs (0.74±0.50), t=3.178, P<0.01)], hemorrhage [(0.30±0.39) vs (0.10±0.21), t=3.090, P<0.01)], disorganization of the microvascular array [(0.38±0.38) vs (0.18±0.32), t=2.729, P<0.01)] were significantly higher than CTD. ③ The NFC of SSc patients was significantly different from CTD. The number of capillary loss ( Z=-4.194, P<0.01), input capillary dimensions ( t=3.704, P<0.01), output capillary dimensions ( t=3.913, P<0.01), wide diameter of capillary ( t=4.586, P<0.01), tortuous capillaries ( Z=-2.677, P<0.01), gaint capillary ( χ2=8.040, P=0.013), effusion ( Z=-2.278, P=0.023) were more increased than CTD. ④ The NFC pattern of SSc with lung involvement were mainly active and late (66%, 33/50), whereas early and active pattern (60%, 6/10) for those without respiratory system involvement ( Z=10.114, P=0.045) . The NFC pattern of SSc patients with joint involvement were mainly active and late (75%, 12/16), whereas early and active (66%, 29/44) for those without joint involvement ( Z=5.550, P=0.057) . Conclusion:The NFC of SSc patients is significantly different from CTD. NFC may be a suitable tool for disease evaluation.

The mechanism of Shuyu capsules in treating premenstrual dysphoric disorder caused by liver qi depression based on microdialysis technology from the aspect of Glu-GABA metabolic pathway / 国际中医中药杂志

Objective:To explore the mechanism of premenstrual dysphoric disorder (PMDD) caused by liver-qi depression from the aspect of Glu-GABA metabolic pathways.Methods:Thirty-six rats with similar open field scores and regular estrus cycles were divided into blank group, model group, fluoxetine group, Shuyu capsule group, saikosaponin group and inhibitor group according to the random number table method, with 6 rats in each group. Stereotactic hippocampus surgery was performed during the first estrous cycle reception period after the estrus cycle was determined. In the non-receiving period of the third and fourth estrus cycles, the restraint model was constructed, and from the first day of the modeling, rats of the fluoxetine group were given fluoxetine capsules 2.67 mg/kg, while rats of the Shuyu capsule group and saikosaponin group were given Shuyu capsules 0.408 g/kg and saikosaponin 0.72 mg/kg once a day for 5 consecutive days. Rats in the inhibitor group were injected with 20 μl L-malic acid with 5 mmol/L concentration, which is an inhibitor of glutamate decarboxylase (GAD), in the hippocampus on the last day of modeling. After the administration, weighed the rats and carried out open field experiments. During the second and fivth estrus cycles of rats, the extracellular fluid of the hippocampus was collected by microdialysis technology, and the content of Glu and GABA in the dialysate was detected by HPLC-FLD. Results:After 5 days of administration, compared with the model group, the body weight of rats in the Shuyu capsule group, the inhibitor group and the fluoxetine group increased ( P<0.05), and the total score of the open field experiment decreased ( P<0.05); compared with the model group, during the receiving period of the five estrus cycle, the Glu level of the Shuyu capsule group and the inhibitor group decreased ( P<0.05); In the non-receiving period of the fifth estrus cycle, the Shuyu capsule group, Glu level of the fluoxetine group and the saikosaponin group increased, GABA level of Shuyu capsule group, inhibitor group and fluoxetine group decreased ( P<0.05), Glu/GABA level of Shuyu capsule group, fluoxetine group and inhibitor group (1.49 ± 0.13, 1.32 ± 0.33, 3.92 ± 0.79 vs. 0.35 ± 0.48) was higher than that of the model group ( P<0.05). Conclusion:The therapeutic mechanism of Shuyu capsule in the treatment of PMDD caused by liver Qi depression rats may be ascribed to inhibiting GAD from Glu-GABA metabolic pathway.