ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

ObjectiveTo confirm the clinical efficacy and safety of Yishen Yangxin Anshen tablets in the treatment of insomnia （heart-blood deficiency and kidney-essence insufficiency syndrome）. MethodA randomized block， double-blind， placebo-controlled， multi-center clinical trial design method was adopted， and a total of 480 patients with insomnia due to deficiency of heart blood and insufficiency of kidney essence （treatment group-control group 3∶1） from seven hospitals （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， The First Clinical Hospital， Jilin Province Academy of Traditional Chinese Medicine（TCM）， The Second Affiliated Hospital of Liaoning University of TCM， The First Affiliated Hospital of Henan University of Chinese Medicine， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine） were enrolled. The treatment group was given Yishen Yangxin Anshen tablets and the control group received placebo tablets （4 tablets/time， 3 times/day， 4 weeks of administration， 4 weeks of follow-up after drug withdrawal）. The sleep dysfunction rating scale （SDRS） score， pittsburgh sleep quality index （PSQI） score， TCM， polysomnography （PSG） indicators from four hospital （Guang'anmen Hospital， China Academy of Chinese Medical Sciences， Henan Province Hospital of TCM， Hebei General Hospital， The First Hospital of Hunan University of Chinese Medicine）， and other efficacy indicators were compared between the two groups before and after treatment. Through general physical examination， laboratory examination， and observation of adverse events， the safety of the drugs was evaluated. ResultThe baseline indexes of the two groups showed no significant difference and thus the two groups were comparable. After treatment， the total score of SDRS in the treatment group was lower than that in the control group （P<0.01）. After drug withdrawal for 4 weeks， the total score of SDRS demonstrated no significant change in the treatment group as compared with that at the end of treatment， indicating that the rebound change of curative effect was not obvious. After treatment， the total score of PSQI in the treatment group decreased as compared with that in the control group （P<0.01）， and the change of total score of PSQI in the treatment group was statistically significant （P<0.05） after drug withdrawal for 4 weeks but small， indicating that the rebound change of curative effect was not obvious. After treatment， the total effective rate about the TCM symptoms in the treatment group was higher than that in the control group （χ²=137.521，P<0.01）. After treatment， the disappearance rates of single indexes in the treatment group， such as difficulty in falling asleep， easily waking up after sleeping， early awakening， short sleep time， dreamfulness， palpitation， forgetfulness， dizziness， mental fatigue， and weakness of waist and knee， increased compared with those in the control group （P<0.01）. After treatment， the treatment group demonstrated fewer awaking times （AT）， longer total sleep time （TST）， lower ATA/TST ratio， and higher sleep efficiency （%） than the control group （P<0.05）. No abnormal value or aggravation related to drugs was observed in either group. The incidence of adverse events in the treatment group and the control group was 5.57% and 8.40% respectively. No serious adverse events or adverse events leading to withdrawal happened in either group. ConclusionYishen Yangxin Anshen tablets is effective and safe for patients with insomnia of deficiency of heart-blood and insufficiency of kidney-essence.

As confusion mounts over RNA isoforms involved in phenotypic plasticity, aberrant CpG methylation-mediated disruption of alternative splicing is increasingly recognized as a driver of intratumor heterogeneity (ITH). Protease serine 3 (PRSS3), possessing four splice variants (PRSS3-SVs; PRSS3-V1-V4), is an indispensable trypsin that shows paradoxical effects on cancer development. Here, we found that PRSS3 transcripts and their isoforms were divergently expressed in lung cancer, exhibiting opposing functions and clinical outcomes, namely, oncogenic PRSS3-V1 and PRSS3-V2 versus tumor-suppressive PRSS3-V3, by targeting different downstream genes. We identified an intragenic CpG island (iCpGI) in PRSS3. Hypermethylation of iCpGI was mediated by UHRF1/DNMT1 complex interference with the binding of myeloid zinc finger 1 (MZF1) to regulate PRSS3 transcription. The garlic-derived compound diallyl trisulfide cooperated with 5-aza-2'-deoxycytidine to exert antitumor effects in lung adenocarcinoma cells through site-specific iCpGI demethylation specifically allowing MZF1 to upregulate PRSS3-V3 expression. Epigenetic silencing of PRSS3-V3 via iCpGI methylation (iCpGIm) in BALF and tumor tissues was associated with early clinical progression in patients with lung cancer but not in those with squamous cell carcinoma or inflammatory disease. Thus, UHRF1/DNMT1-MZF1 axis-modulated site-specific iCpGIm regulates divergent expression of PRSS3-SVs, conferring nongenetic functional ITH, with implications for early detection of lung cancer and targeted therapies.

Objective:To introduce the surgical method of Ortho-Bridge system (OBS) in the treatment of distal femoral fractures in elderly patients and investigate its clinical effect.Methods:From January 2018 to July 2021, 24 elderly patients who suffered distal femoral fractures were treated with bilateral OBS. There were 8 males and 16 females aging from 62 to 87 years, with an average age of 72.6 years. It included 15 cases of simple distal femoral fractures. According to AO classification, there were one case of A1, two of A2, five of A3, two of C1, three of C2 and two of C3. Nine cases of femoral periprosthetic fractures after total knee arthroplasty (TKA) were classified as type II according to rorabeck's classification. After operation, all patients were guided to perform knee joint functional exercise and to measure the range of motion of the knee joint. Then imaging examinations were used to evaluate the fracture healing and measure the femoral-tibial and femoral angles. The American Hospital for Special Surgery (HSS) knee joint scoring system was used to evaluate the knee function.Results:All 24 patients successfully completed the operation. The operation time was 84-115 min, with an average of 96.6 min; the intraoperative blood loss was 150-335 ml, with an average of 240 ml. All patients were followed up for 8-17 months, with an average of 13.6 months. Except for 1 case of nonunion due to few primary bone grafts, which required secondary bone grafting, the other 23 cases achieved bone union. The healing time was 3.5-6 months, with an average of 4.6 months. At 1, 3, and 6 months after operation and at the last follow-up, the flexion angles of knee were 92.2°±10.2°, 98.6°±13.3°, 106.4°±13.7°, 115.7°±15.3°, and the extension angles were -4.7°±4.1°, -1.2°±4.2°, 0.7°±4.5°, 1.8°±4.6°, respectively; and all differences were statistically significant ( F=17.03 and 12.68, P<0.001). The knee flexion and extension angles at the last follow-up were greater than 1, 3, and 6 months after operation, and the differences were statistically significant ( P<0.001). The femoral-tibial angle was 171.2°±2.4° and 170.7°±3.2°, and the femoral angle was 80.3°±1.7° and 79.6°±2.1°, respectively, at the immediate postoperative and last follow-up, with no significant difference. The HSS scores at 1, 3, 6 months after operation and at the last follow-up were 71.5±7.5, 74.6± 9.3, 78.9±10.4 and 84.7±9.4 respectively, with significant difference ( F=9.17, P<0.001). At the last follow-up, the HSS score was higher than that at 1, 3, and 6 months after the operation, and the differences were statistically significant ( P<0.001), and the knee function was evaluated according to the HSS scoring system: excellent in 12 cases, good in 9, fair in 3, with an excellent and good rate of 88% (21/24). There was no OBS crack or fixation failure in all patients, and no prosthetic loosening and instability occurred in patients with periprosthetic femoral fractures after TKA. Statistical analysis of the data at the last follow-up between the distal femoral fracture group and the periprosthetic femoral fracture group after TKA showed that the knee flexion function and HSS score of the periprosthetic femoral fracture group after TKA (126.8°±3.7°, 92.2±4.1) were both better than the simple distal femur fracture group (108.9°±15.7°, 80.2±8.8). The difference was statistically significant ( t=4.22, 4.52, P<0.05). One patient had incision fat liquefaction and healed after debridement; bone nonunion occurred in 1 case, which healed after iliac bone grafting. Conclusion:Double OBS has a good clinical effect in the treatment of distal femoral fractures in the elderly, especially in patients with periprosthetic femoral fractures after TKA.

Objective:To compare the biomechanical parameters of Ortho-Bridge system (OBS) and locking compression plate+locking attachment plate (LCP+LAP) in the fixation of femoral periprosthetic type B1 fracture.Methods:The same periprosthetic type B1 fracture of human femur were made, including simple fracture model and comminuted fracture model, 12 in each. And the simple fracture models were randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP+LAP system fixation group, and the complex fracture models were also randomly divided into 6 pieces of OBS system fixation group and 6 pieces of LCP + LAP system fixation group. Then the four groups of models were tested by axial compression and torsion tests, and the stiffness of the models under axial compression and torsion angle of the models under torsion test were collected. The axial compression failure test was carried out to collect the vertical load of the ultimate failure test. The axial stiffness, torsion angle and axial failure load of OBS and LCP+LAP fixed simple and comminuted fractures were statistically analyzed by t test. Results:For the test of fixed simple fracture, there was no significant difference ( t=0.535, P=0.522) in the axial stiffness between the OBS group (868.87±157.14 N) and the LCP+LAP group (904.53±44.76 N), whereas the results of torsion test showed that the LCP+LAP group had a higher torsion angle 7.17°±0.52° than the OBS group 5.45°±0.44° ( t=5.616, P<0.001); When fixing comminuted fractures, the OBS group had a higher axial stiffness (145.33±10.34 N) than the LCP+LAP group (84.15±8.94 N) ( t=10.961, P<0.001), but the LCP+LAP group had a higher torsion angle 7.75°±1.17° than the OBS group 5.23°±0.31° ( t=4.652, P=0.001). Ultimate failure test data showed that the failure pressure of OBS fixed group (4 967.49±132.88 N) was higher than LCP+LAP group (3 967.41±145.16 N) ( t=12.447, P<0.001). In the LCP+LAP group, there was destruction of the contact cortex at the fracture site, while in the OBS group, there was destruction of the contact cortex at the fracture site as well as fractures around the proximal fixation screw. Conclusion:OBS group has similar axial compression resistance to LCP+LAP group, but better torsion resistance than LCP+LAP group when it is used to fix B1 simple fracture around femoral prosthesis. When comminuted fracture is fixed, the axial compression resistance and torsion resistance of OBS group are better than LCP+LAP group. The stress is dispersed during OBS fixation, which can better avoid the failure of internal fixation during early functional exercise.

OBJECTIVE To study the nephrotoxicity of the extracts from different parts o f Miao medicine Wikstroemia indica in healthy rats ，and to provide reference for the study of its toxicity mechanism and clinical drug use. METHODS Using 70％ ethanol as solvent ，total ethanol extract of W. indica was extracted with diacolation method. After dispersing the above extract with water，the fractions of corresponding fractions were obtained with petroleum ether ，ethyl acetate and n-butanol，and the rest was the extract of water fraction. SD rats were randomly divided into total ethanol extract group ，petroleum ether fraction group ，ethyl acetate fraction group ，n-butanol fraction group ，water fraction group and blank group ，with 12 rats in each group （half male and half female ）. The rats in the administration groups were given the corresponding dose of drug solution intragastrically （total ethanol extract 317.520 mg/kg，petroleum ether fraction 7.875 mg/kg，ethyl acetate fraction 78.435 mg/kg，n-butanol fraction 53.865 mg/kg and water fraction 76.545 mg/kg），once a day ，for conse- cutive 2 weeks，and then stopped taking drug for 2 weeks； rats in the blank group were given equal volume of 1.0％ . sodium carboxymethyl cellulose solution intragastrically. Duringthe experiment ，the general conditions of rats were observed. The samples of urine （on the 14th and 28th day ），serum and bilateral renal tissues （on the 15th and 29th day ）were taken respectively，the renal index was calculated ，the levels of @qq.com renal function indexes in serum and urine were detected ，and the pathomorphological changes of renal tissues were observed. RESULTS During administration ，compared with blank group ，the rats in the total ethanol extract group and ethyl acetate fraction group showed poisoning behavior and activity characteristics such as mental depression ，decreased activity and diet ，thin stool and decreased body mass. The mental state of the rats in the petroleum ether fraction group ，n-butanol fraction group and water fraction group were slightly worse than that in blank group，and slightly decreased activity and diet as well as thin stool ，and slowly increased body mass were found ；however，there was no significant difference in anal temperature in each group. After 2 weeks of administration ，the renal index in total ethanol extract group ，the serum levels of N-acetylglucosaminidase（NAG），urea nitrogen （BUN）and creatinine （Cr）in total ethanol extract group and ethyl acetate fraction group ，serum level of NAG in n-butanol fraction group and serum level of Cr in water fraction group ，as while as NAG levels in urine of rats in total ethanol extract group and petroleum ether fraction group ，NAG and urinary protein levels in urine of rats in ethyl acetate fraction group were increased significantly （P＜0.05 or P＜0.01）. In the pathomorphological observation ，renal tubules showed different degrees of unclear structure ，cell swelling and a few cell necrosis in the total ethanol extract group ，petroleum ether fraction group and ethyl acetate fraction group ，accompanying by glomerular pyknosis，renal tubular sclerosis and inflammatory cell infiltration ，compared with blank group. After drug withdrawal ，the mental state of rats in the administration groups were significantly improved ，the amount of activity and diet increased ，and the stool tended to be normal. Two weeks after drug withdrawal and recovery ，the levels of above indexes in serum and urine of rats in administration groups returned to be close to that in blank group （P＞0.05）；the glomerular structure of rats in each administration group gradually recovered clearly ，and cell swelling and inflammatory cell infiltration were rare in total ethanol extract group ， petroleum ether fraction group and ethyl acetate fraction group. CONCLUSIONS The total ethanol extract ，petroleum ether fraction and ethyl acetate fraction of Miao medicine W. indica have certain nephrotoxicity and reversibility. The toxic component may

Objective:To investigate the immobilizing effect of full-thickness skin subcutaneous grafting on allogeneic full-thickness skin graft in rats.Methods:The experimental research method was used. The inbred male Brown-Norway rats ( n=10) and Lewis rats ( n=10) were used as donors and recipients respectively. After subcutaneously full-thickness separation of a 2.2 cm×2.2 cm area on the nape of the recipient rat, a full-thickness skin of 2.0 cm×2.0 cm taken from the abdomen of the donor rat was subcutaneously grafted, and the donor site was pulled together and sutured. The autologous skin over the allograft in the recipient rat was excised 5-6 d after grafting, and the stitches were removed 7 d after excision. Within 2 months after grafting, the feeding, activity, and survival of the donor and recipient rats, behavior of tearing and scratching the wounds of the recipient rats, the wound condition after autologous skin excision in recipient rats, and the survival and hair growth of the grafted allogeneic skin were observed. Results:Within 2 months after grafting, the donor and recipient rats all ate normally and could move freely with no abnormal death. No tearing or scratching of the wounds occurred in recipient rats. There was a small amount of exudation and partial epidermal desquamation after autologous skin excision in recipient rats. All transplanted allografts survived, which were free of infection and necrosis, with new hairs growing out smoothly.Conclusions:The immobilizing method of full-thickness skin subcutaneous grafting of allogeneic full-thickness skin graft in rats is simple and time-saving without postoperative dressing change, with reliable pressure fixation and high survival rate of skin grafts, which can be promoted for animal skin grafting models.

Objective: To explore the clinical effects of expanded forehead flaps in repairing midfacial defects. Methods: From January 2003 to December 2018, 19 patients with midfacial defects were admitted to our unit, including 8 males and 11 females, aged 7 to 52 years. One cylindrical expander with rated capacity ranged from 100 to 170 mL was placed in the forehead of patients in the first stage of expansion, and the total water injection volume was about 2 times of the rated capacity of the expander during 1 to 2 months. The area of midfacial defects was 4 cm×2 cm to 9 cm×5 cm after resection in the second stage surgery. Expanded forehead flaps with vascular pedicle of supratrochlear vessels or frontal branch of superficial temporal vessels were used to repair the midfacial defects, with flap size ranging from 5 cm×2 cm to 16 cm×6 cm. The donor sites were closed by direct suturing. Three weeks later, the pedicle was divided. The complications, blood supply after flap transfer and pedicle division, and the treatment effects during follow-up were observed. Results: Among the patients, flaps of 11 patients had vascular pedicle of supratrochlear vessels; flaps of 8 patients had vascular pedicle of frontal branch of superficial temporal vessels. All the flaps survived with no complications and good blood supply after flap transfer and pedicle division. During the follow-up of 6 to 12 months after the third stage surgery of pedicle division of 12 patients, no lower eyelid ectropion occurred, the appearance of the flaps was similar to the surrounding tissue with no swelling. Conclusions The application of expanded forehead flaps can not only repair the defects but also effectively avoid the complication of lower eyelid ectropion, which is a promising method in repairing midfacial defects.

Objective: To investigate the functional recovery and cosmetic effects of pre-expanded pedicled deltopectoral flap. Methods: From January 2008 to December 2018, 42 patients with 56 pre-expanded pedicled deltopectoral flaps from Xijing Hospital of Air Force Military Medical University were followed up at least 6 months. 18 of them were male, the remaining were female. And the average age was (24.7±7.3) years. Then the indicators were tested and evaluated. Tubes with different temperatures were used for temperature sensation test. The flaps were stabbed using a 27 G blunt needle to test algesthesia. Tactile threshold was measured by Semmes-Weinstein monofilament. Two-point discrimination was measured by Disk-Criminator. Elasticity of skin flaps was measured by CK-MC®960. Colors of skin flaps were analyzed by ANTERA®3D system, including L^*a^*b^*, melanin and hemoglobin content. And the postoperative scars were evaluated by the Patient and Observer Scar Assessment Scale (POSAS). The flap retraction rate [(flap area immediately after operation-flap area at the follow-up time)/flap area immediately after operation]was calculated. The satisfaction of patients, doctors and third parties was investigated as well. Statistical analysis of data was performed with SPSS 23.0, satisfaction rate was expressed as percentages. Scar scores were compared by Wilcoxon rank sum test. The values of elasticity, color L^*a^*b^*, melanin and hemoglobin between skin flaps and normal skin were analyzed by paired t test. The difference was statistically significant at P<0.05. Results: The scores of pain, heat and cold sensation were (4.61±0.78), (3.48±0.90) and (4.39±0.81), the tactile threshold was (0.26±0.23) g/mm², and the distance of two-point discrimination was (10.09±4.79) mm. There was no significant difference in elasticity, color b^*and melanin content between skin flap and normal skin of face and neck (P>0.05). The color of flap L^*, a^*and hemoglobin content of flaps were significantly different from those of normal skin from face and neck (P<0.05). The result of self-assessment of patients (POSAS) showed that there were significant differences (P<0.05) in pain, itch and stiffness between facial and chest donor scar. The result of observer evaluation (POSAS) showed that the scar score for all items around facial flap was better than that of chest donor area, the difference was statistically significant (P<0.05), and the retraction rate of flaps was (10.44 ±3.36)%. The satisfaction rates of doctors, patients and the third party were 92.86% (39/42), 71.43% (30/42) and 61.90% (26/42), respectively. Conclusions Excellent functional recovery and reliable cosmetic effect were observed in the facial-cervical scar repair with pre-expanded pedicled deltopectoral flap. Transfer of pre-expanded pedicled deltopectoral flap is an effective method for the treatment of facial-cervical scars.

Objective: To investigate the efficacy and outcome of transcatheter patent foramen ovale (PFO) closure in patients with cryptogenic stroke (CS). Methods: Sixty consecutive patients with cryptogenic stroke who undertook transcatheter PFO closure between May 2015 and September 2017 in Beijing Tiantan Hospital were enrolled in this prospective study.Transcranial Doppler (TCD) bubble test was performed and right-left shunt(RLS) was confirmed in all patients.Closure success rate,effective closure rate, complications, recurrence of ischemic stroke and new onset atrial fibrillation were evaluated. Results: A total of 60 patients (42 male,age range 24-68 (47±11)years) were included in the study.PFO size (motionless state) was (1.6±0.6)mm.RLS before closure was graded and 11 patients had moderate RLS and 48 patients had large RLS (include 41 patients who experienced shower or curtain effect).Closure success rate was 100% (60/60).No severe complications were observed.At 6 months,45 patients completed TCD bubble test.Of these, 4 patients suffered from moderate to large residual and thus effective closure rate was 91%(41/45).The mean follow-up period was 2-29 (median 12) months. During the follow-up, only 1 patient experienced recurrent cerebral infarction.New onset atrial fibrillation was not detected. Conclusion Transcatheter PFO closure is effective,safe and related with a good outcome in reduction of recurrent CS for patients with PFO.