Effectiveness analysis of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff / 中国修复重建外科杂志

OBJECTIVE@#To investigate the feasibility and effectiveness of "tail compression fixation+suture bridge" technology under shoulder arthroscopy for treating primary tear in medial enthesis of rotator cuff.@*METHODS@#The clinical data of 11 patients with primary tear in medial enthesis of rotator cuff who met the selection criteria between October 2020 and October 2022 were retrospectively analyzed, including 3 males and 8 females, aged 39-79 years, with an average of 61.0 years. Rotator cuff injury was caused by traumatic fall in 8 cases, and the time from injury to admission was 1-4 months, with an average of 2.0 months; the remaining 3 cases had no obvious inducement. The active range of motion of the affected shoulder was limited, with an active forward flexion range of motion of (64.1±10.9)°, abduction of (78.1±6.4)°, internal rotation of (48.2±6.6)°, and external rotation of (41.8±10.5)°; 5 cases had shoulder stiffness. The preoperative visual analogue scale (VAS) score was 7.8±0.8 and the American Society of Shoulder and Elbow Surgeons (ASES) score was 23.9±6.4. The patients were treated with "tail compression fixation+suture bridge" technology under shoulder arthroscopy, and the pain and functional recovery were evaluated by VAS score, ASES score, and active range of motion of shoulder joint at last follow-up; MRI was performed after operation, and the integrity of rotator cuff was evaluated by Sugaya classification system.@*RESULTS@#All the 11 patients were followed up 2-22 months, with an average of 13.5 months. All incisions healed by first intention, and there was no complication such as infection, rotator cuff re-tear, and anchor falling off. At last follow-up, the VAS score was 0.8±0.7 and the ASES score was 93.5±4.2, which significantly improved when compared with those before operation ( P<0.05). All 11 patients had no significant swelling in the shoulders, and the active range of motion was (165.1±8.8)° in flexion, (75.3±8.4)° in abduction, (56.6±5.5)° in internal rotation, and (51.8±4.0)° in external rotation, which significantly improved when compared with those before operation ( P<0.05). Shoulder MRI showed adequate tendon thickness and good continuity in 9 cases, including 4 cases with partial high signal area; and 2 cases with inadequate tendon thickness but high continuity and partial high signal area. According to Sugaya classification system, there were 4 cases of type 1 (36.4%), 5 cases of type 2 (45.5%), and 2 cases of type 3 (18.1%).@*CONCLUSION@#For the patients with primary tear in medial enthesis of rotator cuff, the "tail compression fixation+suture bridge" technology under shoulder arthroscopy is simple and effective.

Juniperus communis extract induces cell cycle arrest and apoptosis of colorectal adenocarcinoma in vitro and in vivo

Juniperus communis (JCo) is a well-known traditional Chinese medicinal plant that has been used to treat wounds, fever, swelling, and rheumatism. However, the mechanism underlying the anticancer effect of JCo extract on colorectal cancer (CRC) has not yet been elucidated. This study investigated the anticancer effects of JCo extract in vitro and in vivo as well as the precise molecular mechanisms. Cell viability was evaluated using the MTT assay. Cell cycle distribution was examined by flow cytometry analysis, and cell apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Protein expression was analyzed using western blotting. The in vivo activity of the JCo extract was evaluated using a xenograft BALB/c mouse model. The tumors and organs were examined through hematoxylin-eosin (HE) staining and immunohistochemistry. The results showed that JCo extract exhibited higher cytotoxicity against CRC cells than against normal cells and showed synergistic effects when combined with 5-fluorouracil. JCo extract induced cell cycle arrest at the G0/G1 phase via regulation of p53/p21 and CDK4/cyclin D1 and induced cell apoptosis via the extrinsic (FasL/Fas/caspase-8) and intrinsic (Bax/Bcl-2/caspase-9) apoptotic pathways. In vivo studies revealed that JCo extract suppressed tumor growth through the inhibition of proliferation and induction of apoptosis. In addition, there was no obvious change in body weight or histological morphology of normal organs after treatment. JCo extract suppressed CRC progression by inducing cell cycle arrest and apoptosis in vitro and in vivo, suggesting the potential application of JCo extract in the treatment of CRC.

Analysis of the effect of target-directed treatment based on nutrition-oriented information software on nutritional compliance rate in adults with severe traumatic brain injury: a mixed cohort study / 中华危重病急救医学

Objective:To analyze the effect of target-oriented treatment based on nutrition-oriented information software on nutritional standards of adult patients with severe traumatic brain injury (sTBI).Methods:Adult patients with sTBI admitted to the department of emergency intensive care unit (EICU) of Huzhou First People's Hospital were enrolled. Taking the online time of information software as the node on March 1st 2019, the patients who underwent early standardized enteral nutrition (EN) process from March 1st 2018 to February 28th 2019 were taken as the control group. The patients who received nutrition management by the nutritional support management system software for critical patients from March 1st 2019 to February 29th 2020 were used as the experimental group. The software was integrated with critical information system software. The effects of nutritional support in two groups were evaluated, including starting time of EN; total energy supply, total protein supply, energy compliance rate on 7 days and 14 days; the total albumin. And the related indicators of critical illness management were evaluated, including the survival rate of intensive care unit (ICU) at 28 days, duration of invasive mechanical ventilation (IMV), successful rates of weaning from IMV, rapid shallow breath index (RSBI) after spontaneous breathing test (SBT), serum cholinesterase on 7 days and 14 days, etc.Results:Fifty-one patients with sTBI were included in the analysis, 28 in the control group and 23 in the experimental group. There were no significant differences in baseline data between the two groups, such as gender, age, body mass index (BMI), acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score, nutritional risk score (NUTRIC), etc., which were comparable. Compared with the control group, the starting time of EN in experimental group was significantly earlier (hours: 26.82±8.33 vs. 36.73±12.86, P = 0.046). The total protein supply on 7 days and 14 days [g·kg -1·d -1: 1.87 (1.36, 1.92) vs. 1.02 (0.87, 1.67), 2.63 (1.49, 1.92) vs. 1.23 (0.89, 1.92), both P < 0.05], the total energy supply on 14 days (kJ·kg -1·d -1: 154.26±68.16 vs. 117.99±112.42, P = 0.033), the energy compliance rate on 14 days [80.0% (16/20) vs. 35.7% (10/28), P = 0.002], and the serum cholinesterase on 14 days [U/L: 5 792.5 (4 621.0, 8 131.0) vs. 4 689.7 (3 639.0, 7 892.0), P = 0.048] in experimental group were significantly increased. There were no significant differences in other indicators between the two groups [total energy supply on 7 days (kJ·kg -1·d -1): 91.50±30.50 vs. 92.88±28.16, P = 0.184; energy compliance rate on 7 days: 34.7% (8/23) vs. 21.4% (6/28), P = 0.288; total albumin (g): 97.80±46.29 vs. 114.29±52.68, P = 0.086; 28-day survival rate of ICU: 87.0% vs. 78.6%, P = 0.081; duration of IMV (days): 14.33±7.68 vs. 15.68±6.82, P = 0.074; successful rates of weaning from IMV: 69.6% vs. 67.9%, P = 0.895; RSBI after SBT (breaths·min -1·L -1): 26.84±10.69 vs. 33.68±8.94, P = 0.052; serum cholinesterase on 7 days (U/L): 4 289.7 (2 868.0, 7 291.0) vs. 3 762.2 (2 434.0, 6 892.0), P = 0.078]. Conclusion:The development and clinical application of nutrition support information software is helpful for the standardized implementation of the nutritional support treatment process for adult patients with sTBI, which is worthy of further clinical research and promotion.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

Significance of spinal sagittal balance for guiding acetabular prosthesis positioning / 中国骨伤

Since the concept of "safe area" put forward by Lewinnek, it has been widely recognized. While in recent years, many scholars have found that even if the acetabular prosthesis was placed on the "safe area", there were still many unexplained dislocation after total hip arthroplasty. And scholars began to question whether the "safe area" is really suitable for all patients. Spinal degeneration, deformity, lumbar fusion, etc. will lead to spine sagittal imbalance and changes in pelvic activity, which could lead to changes in acetabular orientation, and ultimately lead to edge loading, wear, impact, and even dislocation after total hip replacement. From the perspective of wear, impact and dislocation, it is determined by the functional positioning of the acetabular cup, not the anatomical positioning. The anatomical positioning and functional positioning of the neutral pelvic acetabular cup in the standing position can be considered equivalent. For pelvic rotation more than 20°, functional placement needs to be considered. In recent years, as the understanding of the internal relationship between the spine-pelvis-hip joint has become more and more profound, some scholars further classify the hip-spine relationship according to whether the spine is stiff or deformed, and propose corresponding acetabulums according to different types of hip-spine relationships The function of placement, so as to achieve a stable artificial hip joint. Therefore, it is of great significance to fully assess whether the patient's sagittal plane is balanced before surgery to guide artificial hip replacement surgery.

Long Noncoding RNA PVT1 Promotes Stemness and Temozolomide Resistance through miR-365/ELF4/SOX2 Axis in Glioma

Long non-coding RNA (lncRNA) are a class of non-coding RNAs demonstrated to play pivotal roles in regulating tumor progression. Therefore, deciphering the regulatory role of lncRNA in the development of glioma may offer a promising therapeutic target for treatment of glioma. We performed RT-qPCR analysis on the expression of lncRNA plasmacytoma variant translocation 1 (PVT1) and miR-365 in glioma tissues and cell lines. Cell proliferation and viability was assessed with CCK8 assay. Cell migration was assessed by wound healing assay. Transwell assay was used to assess cell invasion capacity. Expression of CD133+ cells was detected by flow cytometry. Western blot assay was used to detection the expression of ELF4 and stemness-related protein SOX2, Oct4 and Nanog. Bioinformatics and dual-luciferase assay were used to predict and validate the interaction between PVT1 and miR-365. Elevated PVT1 expression was observed in glioma tissues and cells. Knockdown of PVT1 and overexpression of miR-365 inhibited proliferation, migration, invasion and promoted stemness and Temozolomide (TMZ) resistance of glioma cells. PVT1 regulated ELF4 expression by competitively binds to miR-365. PVT1 regulated the stemness and sensitivity of TMZ of glioma cells through miR-365/ELF4/ SOX2 axis. This study identified that PVT1 promoted glioma stemness through miR-365/ELF4/SOX2 axis.

Prognostic evaluation of P53 and BCL2 proteins in MYC/BCL2 double expression DLBCL / 中华血液学杂志

Objective@#To investigate the strong expression (S+) of P53 and BCL2 proteins in MYC/BCL2 double-expression DLBCL (DEL) and whether they can be used for the prognostic evaluation and stratified diagnosis of DELs.@*Methods@#Tissue microarray were made by filed FFPE blocks of 174 DLBCL cases. The translocation of MYC, BCL2 and BCL6 genes were detected by FISH, and the proteins were detected by IHC. Data of clinicopathologic features and follow up of patients were collected and OS (overall survival) and PFS (progression free survival) were analyzed by statistics.@*Results@#Eight double-hit lymphomas (DHLs) were identified in all cases, and 45 DELs were selected from 166 remaining cases, which have no significant difference in OS and PFS compared with non-DEL cases (P=0.668 and P=0.790) . Of 42 DEL-cases with follow up data, 24 cases with P53+ or/and BCL2 (S+) are significantly shorter OS and PFS than others (P=0.003 and P=0.000) , in which the cases with P53+/BCL2 (S+) co-expression were the worst prognosis, and P53/BCL2 co-weaker positive DEL cases even have superior OS and PFS than those non-DELs. Although statistics showed that the cases of P53+ or/and BCL2 (S+) have a lower OS and PFS in total cases (P=0.063 and P=0.024) , it is not the case when the DEL-cases take out from total cases, that is the cases with P53+ or/and BCL2 (S+) are as similar OS and PFS as others in non-DEL group (P=0.590 and P=0.550) .@*Conclusion@#The strong expression of P53 and BCL2 proteins can be used as indicators of stratified diagnosis and poor prognosis of DEL.

Analysis of the effect about tubularized urethral plate disassembly for one-stage midshaft epispadias repair in infant / 中华泌尿外科杂志

Objective@#To evaluate the safety and efficacy of tabularized urethral plate disassembly for epispadias repair in infant.@*Methods@#From January 2016 to September 2018, 10 boys aged between 18 to 36 months old with mishaft epispadias were included. The main complaint was that the urethral opening was found on the dorsal side of the penis. Preoperative cystography revealed that 3 of them had unilateral vesicoureteral reflux (Grade Ⅰ), and white blood cells in routine urinary in all 10 patients were negative. Physical examination: the penis is short and flat, the width is 17-25 mm, average is 20.7 mm, the penis curvature is 15°-30°, average is 21.5°, and the urethral opening located on the dorsal side of the penis. The anesthesia method was selected for tracheal intubation, intravenous anesthesia combined with caudal anesthesia, and the surgical position was supine position. The surgical method: one stage of tabularized urethral plate disassembly urethroplasty: during the operation, the penile curve was corrected by free urethral plate and penile degloving. Two of them were unsatisfied with the correction of the curvature, and the ventral tunica folded was applicate. To avoid urethral plate ischemia, attention should pay to blood supply protection. The two corpus cavernosum are separated in the root, and the urethra is completely displaced to the ventral side of the cavernous body. The ventral side of the urethral under glans is shaped into a fissured that conforms to the anatomy. The prognosis and surgical choice of the midshaft epispadias were discussed combined with literature.@*Result@#The operation time was 130-200 min with an average of 157 mins. Intraoperative hemorrhage 5-30 ml, average is 16 ml, 1 case of glans skin was black one day after surgery, with enhanced dressing change. After 1 month, the glans was local atrophy and scar formation. No skin incision infection case. After discharge from the hospital, the follow up through the internet and outpatients for 3-40 months, average is 21 months, 2 cases with urethral fistula, more surgery to repair the fistula successfully after 6 months. The penile curvature was corrected in 8 cases, and the residual curvature of 2 cases was about 10-15°, which was temporarily observed. Patients with unilateral vesicoureteral reflux preoperatively, they still suffered from vesicoureteral reflux in the 6-12 months regular review after surgery without any intervention due to white blood cell was negative in urine routine. All cases had urinary patency and no cases with urethral stricture.@*Conclusion@#Tubularized urethral plate disassembly is a effective and simple procedure that can correct the midshaft epispadias in infant.

Analysis of the effect about tubularized urethral plate disassembly for one-stage midshaft epispadias repair in infant / 中华泌尿外科杂志

Objective To evaluate the safety and efficacy of tabularized urethral plate disassembly for epispadias repair in infant.Methods From January 2016 to September 2018,10 boys aged between 18 to 36 months old with mishaft epispadias were included.The main complaint was that the urethral opening was found on the dorsal side of the penis.Preoperative cystography revealed that 3 of them had unilateral vesicoureteral reflux (Grade Ⅰ),and white blood cells in routine urinary in all 10 patients were negative.Physical examination:the penis is short and flat,the width is 17-25 mm,average is 20.7 mm,the penis curvature is 15°-30°,average is 21.5°,and the urethral opening located on the dorsal side of the penis.The anesthesia method was selected for tracheal intubation,intravenous anesthesia combined with caudal anesthesia,and the surgical position was supine position.The surgical method:one stage of tabularized urethral plate disassembly urethroplasty:during the operation,the penile curve was corrected by free urethral plate and penile degloving.Two of them were unsatisfied with the correction of the curvature,and the ventral tunica folded was applicate.To avoid urethral plate ischemia,attention should pay to blood supply protection.The two corpus cavernosum are separated in the root,and the urethra is completely displaced to the ventral side of the cavernous body.The ventral side of the urethral under glans is shaped into a fissured that conforms to the anatomy.The prognosis and surgical choice of the midshaft epispadias were discussed combined with literature.Result The operation time was 130-200 min with an average of 157 mins.Intraoperative hemorrhage 5-30 ml,average is 16 ml,1 case of glans skin was black one day after surgery,with enhanced dressing change.After 1 month,the glans was local atrophy and scar formation.No skin incision infection case.After discharge from the hospital,the follow up through the internet and outpatients for 3-40 months,average is 21 months,2 cases with urethral fistula,more surgery to repair the fistula successfully after 6 months.The penile curvature was corrected in 8 cases,and the residual curvature of 2 cases was about 10-15°,which was temporarily observed.Patients with unilateral vesicoureteral reflux preoperatively,they still suffered from vesicoureteral reflux in the 6-12 months regular review after surgery without any intervention due to white blood cell was negative in urine routine.All cases had urinary patency and no cases with urethral stricture.Conclusion Tubularized urethral plate disassembly is a effective and simple procedure that can correct the midshaft epispadias in infant.

Application of Mitrofanoff procedure in pediatric lower urinary tract dysfunction / 中华泌尿外科杂志

Objective To discuss the treatment effect with Mitrofanoff procedure in lower urinary tract of pediatric patients.Methods 9 patients conducted Mitrofanoff procedure from January 2014 to January 2018 in our center were analyzed retrospectively.There were 2 boys and 7 girls,age from 4 to 14 years old (7.3 years old in average).1 child was diagnosed as bladder exstrophy,4 children were neurogenic bladder,2 children were bladder tumor and the other 2 were urethral trauma.All patients were conducted Mitrofanoff procedure under general anesthesia,used appendix as the conduit,3 patients used their original bladder as reservoir,bladder augmentation was employed in 4 patients and ileal neobladder was employed in 2 patients to construct reservoir.The distal of appendix was inserted into submucosal of reservoior and the proximal end was connected to the umbilical or lower abdominal wall.Results The operations were all successfully completed without sever complications,the time spent was 176-210 min,190 min in average,hemorrhage amount 20-35 ml.Patients were followed up 15 to 50 months,the bladder capacity is 80 to 120 ml.Hydronephrosis was improved compared with pre-operative condition.4 children diagnosed with neurogenic bladder still suffered vesical ureteral reflux.All patients can conduct clean intermittent catheterization without difficulty.There was no leakage of urine from the stoma,while 2 patients showed leakage of urine from urethra when exercising,so we closed the bladder neck 6 month later.Conclusion Mitrofanoff procedure can be implied in children with end-staged lower urinary tract dysfunction due to nerogenic bladder,bladder tumor,bladder exstrophy,which makes intermittent catheterization become more convenient.

Feasibility and safety of prostatic vaporization using 180W greenlight system in day surgery mode / 中华泌尿外科杂志

Objective To evaluate the feasibility and safety of 180W greenlight laser in the treatment of benign prostatic hyperplasia (BPH) in the day surgery mode.Methods A retrospective review included 65 patients with benign prostate hyperplasia who were treated with photoselective vaporization of the prostate (PVP) under 180W greenlight system from Jan 2017 to Jan 2018,was performed.The patients' age ranged from 54 to 75 years old and the prostatic volume ranged from 42 to 93 ml.All patients were classified into two groups [day sugery group (n =29) and inpatient surgery group(n =36)] based on the wishes of patients.In day sugery group,the admission,operation and discharge were completed in 24 hours.The preoperative clinic parameters such as prostate volume,IPSS,Qmax QOL and PVR were recorded in the two groups.The prostatic volume in two groups was (67.3 ± 15.9) ml and (70.4 ± 16.1) ml,respectively.The IPSS and QOL scores in two groups were (23.2±4.6 vs.23.9±4.5) and (4.7±0.9 vs.4.4± 0.8),respectively.The Q and PVR in two groups were [(6.7 ± 2.5) ml/s vs.(6.8 ± 2.8) ml/s] and [(133.9 ± 81.3) ml vs.(105.8 ± 76.3) ml],respectively.The time of catheterization and postoperative hospitalization,total cost,postoperative adverse events were recorded,too.All the clinic data of preoperation,intraoperation and postoperation were compared between two groups.Results The operations and follow-up were successfully executed in all patients.There were not statistical significance differences in preoperative parameters between the two groups (P ＞ 0.05).There were not statistical significance differences in operating time [(67.8 ± 9.8) min vs.(70.9 ± 12.8) min],laser time [(49.8 ± 8.3) min vs.(51.6±10.4) min],energy used [(295.7±112.6) kJ vs.(285.0±108.2) kJ],between the two groups,too (P ＞ 0.05).A significantly less mean catheter duration,hospital stay and hospital charges were observed in the day surgery group [(14.6 ±2.0)hours,(0.5 ±0) days and (23 279 ±511) yuan,respectively] than in the inpatient surgery group [(51.7 ± 1 1.8) hours,(3.0 ± 0.8) days and (27 452 ± 440)yuan,respectively,P ＜0.05].3 cases of urinary retention and 1 case of gross hematuria after the catheter removal were recorded in the day surgery group,2 cases of urinary retention were recorded in the inpatient surgery group,and all of these 6 cases were cured through indwelling catheter.After 3 months follow up,there were not statistical significant differences io IPSS(12.4 ± 3.3 vs.10.6 ± 4.2),Q [(17.4±2.1)ml/s vs.(17.1 ±1.8) ml/s],and QOL (2.1 ±0.7 vs.2.3±0.7)between the two groups (P ＞ 0.05).However,significant difference of those items could be noticed when compared with those items before surgery (P ＜ 0.05).Conclusions In the day surgery mode,180W greenlight laser vaporization of the prostate is safe and effective,without the increase of surgical complications.The length of stay and hospitalization expenses were much less.Thus,this strategy is worth promoting in clinical practice.

Jiao-tai-wan Up-regulates Hypothalamic and Peripheral Circadian Clock Gene Cryptochrome and Activates PI3K/AKT Signaling in Partially Sleep-deprived Rats / 华中科技大学学报（医学）（英德文版）

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Jiao-tai-wan Up-regulates Hypothalamic and Peripheral Circadian Clock Gene Cryptochrome and Activates PI3K/AKT Signaling in Partially Sleep-deprived Rats / 华中科技大学学报（医学）（英德文版）

This study aims to explore the effect and mechanism of Jiao-tai-wan (JTW) on systemic and tissue-specific inflammation and insulin resistance in obesity-resistant (OR)rats with chronic partial sleep deprivation (PSD).OR rats with PSD were orally given JTW and Estazolam for 4 weeks.The amount of food intake and metabolic parameters such as body weight increase rate,fasting plasma glucose (FPG),fasting insulin (FINS),homeostasis model assessment-insulin resistance (HOMA-IR) and plasma inflammatory markers were measured.The expression levels of circadian proteins cryptochrome 1 (Cry1)and cryptochrome 2 (Cry2) in hypothalamus,adipose and liver tissues were also determined.Meanwhile,the mRNA expression of inflammatory markers,activity of nuclear factor kappa B (NF-κB) p65 protein,as well as the expression levels of insulin signaling pathway proteins in hypothalamus,adipose and liver tissues were measured.Additionally,cyclic adenosine 3',5'-monophosphate (cAMP) and activity of vasodilator-stimulated phosphoprotein (VASP)in hypothalamus tissue were measured.JTW significantly decreased the body weight increase rate and food intake,ameliorated systemic inflammation and insulin resistance.JTW effectively ameliorated inflammation and increased PI3K/AKT signaling activation in hypothalamus,adipose and liver.Interestingly,all these changes were associated with the up-regulation of circadian gene Cryl and Cry2 protein expression.We also found that in hypothalamus tissue of P SD rats,down-regulation of Cry 1 and Cry2 activated cAMP/PKA signaling and then led to inflammation,while JTW inhibited this signaling.These results suggested that JTW has the beneficial effect on ameliorating inflammation and insulin resistance in partially sleep-deprived rats by up-regulating Cry expression.

Mechanisms of resistance to cancer immunotherapy / 中华微生物学和免疫学杂志

Cancer immunotherapy uses the host′s immune system to mobilize immune cells to rec-ognize and eventually eliminate cancer cells .At present, studies in terms of cancer immunotherapy mainly focus on programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) antibody, cytotoxic T-lymphocyte-associated protein 4 ( CTLA-4 ) antibody, chimeric antigen receptor T-cell immunotherapy (CAR-T), T cell receptor Immunotherapy (TCR-T), etc.Despite the fact that cancer immunotherapies elicit unprecedented durable responses in clinical therapy , they appear to be ineffective to some patients .In addition, some responders relapse and show resistance to immunotherapies even if their symptoms are re -lieved for a time .Resistance to cancer immunotherapy can be categorized into primary , adaptive and ac-quired, which can occur in every stage during the process of anti-tumor response.In this review, we discuss the known mechanisms of resistance and provide a rationale for the use of combination therapy to overcome resistance.

Effect of early enteral nutrition standardized treatment on blood glucose and prognosis in acute respiratory distress syndrome patients with mechanical ventilation / 中华危重病急救医学

Objective To study the effect of early entreat nutrition (EN) standardized treatment on optimization of blood glucose control and prognosis in acute respiratory distress syndrome (ARDS) patients with mechanical ventilation (MV). Methods Forty-two patients with MV of ARDS admitted to Huzhou First Municipal People's Hospital from April 2015 to March 2017 were enrolled. April 1st, 2016 was taken as the time node, the patients treated from April 1st, 2015 to March 31st, 2016 were assigned in the control group (n = 20), while the patients treated from April 1st, 2016 to March 31st, 2017 were included in the experimental group (n = 22). The patients in experimental group were given conventional treatment, in 24-48 hours after admission gastrointestinal decompression was stopped and early EN was begun through a nasointestinal tube; the patients in control group received conventional treatment and routine EN (given 48 hours after admission). The differences in nutritional support indexes, the blood glucose variability indexes and the prognostic related indicators were compared between the two groups. Results Compared with the control group, the initiation time for EN tolerance, first defecation time, time of reaching target feeding amount were significantly earlier in the early EN standardized treatment process management [time of initial EN tolerance (hours): 106.82±42.84 vs. 157.29±56.76, first defecation time (hours): 71.29±23.43 vs. 104.69±26.94, time of reaching target feeding amount (days): 6.24±1.25 vs. 9.86±2.36], the proportions of EN/EN+parenteral nutrition (PN) and the nasointestinal tube feeding reaching the standard on 7 days in experimental group were significantly increased [the proportion of EN/EN+PN:98.69% vs. 78.69%, the nasointestinal tube feeding reaching standard: 68.18% (15/22) vs. 45.00% (9/20)], average level of blood glucose (GLUave), maximum value of blood glucose (GLUmax), standard deviation of blood glucose (GLUsd), coefficient of variation of blood glucose (GLUcv), hyperglycemia incidence, incidence of multiple organ dysfunction syndrome (MODS), 28-day mortality were significantly decreased [GLUave (mmol/L): 9.4±2.6 vs. 11.5±3.9, GLUmax (mmol/L): 14.19±2.36 vs. 16.26±4.89, GLUsd (mmol/L): 4.86±1.27 vs. 6.87±2.46, GLUcv: (49.86±6.32)% vs. (59.95±5.81)%, hyperglycemia incidence: 59.09% (13/22) vs. 80.00% (16/20), incidence of MODS: 59.09% (13/22) vs. 80.00% (16/20), 28-day mortality: 36.36% (8/22) vs. 45.00% (9/20)], minimum value of blood glucose (GLUmin) was significantly increased (mmol/L: 5.86±2.32 vs. 4.18±1.86), invasive MV time was significantly shorted (hours:156.82±26.84 vs. 169.93±32.34) with statistically significant differences (all P < 0.05). Early EN could also improve the patient's pulmonary oxygenation function. Since 9 days of disease course, the oxygenation index (PaO2/FiO2) in the experimental group was significantly higher than that of the control group [mmHg (1 mmHg = 0.133 kPa): 256.97±18.63 vs. 239.82±21.72, P = 0.068], but there was no significant difference in the length of ICU stay (days: 13.9±3.6 vs. 14.8±3.4, P > 0.05). Conclusion The early EN standardized treatment process management can improve the nutritional status, decrease blood sugar fluctuations, and further benefit the improvement of the prognosis of ARDS patients with MV.

Serum Gamma-glutamyl Transferase Levels Predict Functional Outcomes after Aneurysmal Subarachnoid Hemorrhage / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>We aim to explore the potential association between serum gamma-glutamyl transferase levels and functional outcome after aneurysmal subarachnoid hemorrhage in a Chinese population.</p><p><b>METHODS</b>A total of 386 aneurysmal subarachnoid hemorrhage patients were included in the study from September 2007 to February 2015. Baseline serum gamma-glutamyl transferase levels and 6-month follow-up functional outcomes were determined. A poor outcome was defined as a modified ranking scale score of ⋝ 3. The multivariable logistic model was used to analyze the relationship between serum gamma-glutamyl transferase and clinical outcomes after aneurysmal subarachnoid hemorrhage.</p><p><b>RESULTS</b>The adjusted poor outcome rates of patients with gamma-glutamyl transferase levels of < 30 U/L, 30-50 U/L and ⋝ 50 U/L were 16.7%, 19.6%, and 34.4%, respectively (P < 0.01). The age-sex and multivariable adjusted odds ratios (95% confidence intervals) of poor prognosis comparing the top group (⋝ 50 U/L) with the lowest group (< 30 U/L) were 5.76 (2.74-12.13), 6.64 (2.05-21.52), and 6.36 (1.92-21.02). A significant linear trend existed between gamma-glutamyl transferase level and aneurysmal subarachnoid hemorrhage prognosis. This association was also observed among nondrinkers.</p><p><b>CONCLUSION</b>Patients with higher gamma-glutamyl transferase levels were more likely to have a poor prognosis. Serum gamma-glutamyl transferase can be considered to be an independent predictor of functional outcomes after aneurysmal subarachnoid hemorrhage.</p>

Effect of Jiaotai Pill () on intestinal damage in partially sleep deprived rats / 中国结合医学杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of Jiaotai Pill (, JTW) on intestinal mucosal damage in rats with chronic partial sleep deprivation (PSD).</p><p><b>METHODS</b>Obesity resistant (OR) rats were selected, and underwent 4 h PSD by being exposed to environmental noise for 4 weeks. During the whole PSD period, JTW and estazolam were orally given to the rats respectively in the treating groups. Plasma concentration of lipopolysaccharide (LPS) which is the marker of gut-origin endotoxemia was examined. Intestinal morphology changes were observed by optical microscopy. The protein expression of occludin (Ocln) in the intestine was measured by immunofluorescence technique and Western blot. The expressions of circadian proteins cryptochromes (Cry1 and Cry2) in the intestine were also determined.</p><p><b>RESULTS</b>The treatment of JTW significantly decreased LPS level in OR rats with PSD (P<0.05). JTW also attenuated insomnia-induced intestinal injury like shorter, sparse and incomplete villus, wide gap between the villus, mucosal swelling and congesting (P<0.05). These changes were associated with the effect of JTW on up-regulating the expressions of Cry1 protein, Cry2 protein and Ocln protein in the intestine.</p><p><b>CONCLUSIONS</b>JTW has the beneficial effect on improving intestinal mucosal damage caused by PSD. The mechanism appears to be related to the modulation of the expressions of circadian proteins and Ocln protein in the intestine, thereby attenuating inflammation and improving insulin resistance in insomnia rats.</p>

Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells / 华中科技大学学报（医学）（英德文版）

Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often aβsociated with insulin resistance and impaired glucose uptake in peripheral tiβsues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the expreβsion of alpha7 nicotinic acetylcholine receptor (α7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β (IKκβ) Ser181/IKKβ and the expression of nuclear factor-kappa B (NF-κB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of AChE activity.

Berberine relieves insulin resistance via the cholinergic anti-inflammatory pathway in HepG2 cells / 华中科技大学学报（医学）（英德文版）

Berberine (BBR) is an isoquinoline alkaloid extracted from Rhizoma coptidis and has been used for treating type 2 diabetes mellitus (T2DM) in China. The development of T2DM is often associated with insulin resistance and impaired glucose uptake in peripheral tissues. In this study, we examined whether BBR attenuated glucose uptake dysfunction through the cholinergic anti-inflammatory pathway in HepG2 cells. Cellular glucose uptake, quantified by the 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-2-deoxy-D-glucose (2-NBDG), was inhibited by 21% after HepG2 cells were incubated with insulin (10(-6) mol/L) for 36 h. Meanwhile, the expression of alpha7 nicotinic acetylcholine receptor (α7nAChR) protein was reduced without the change of acetylcholinesterase (AChE) activity. The level of interleukin-6 (IL-6) in the culture supernatant, the ratio of phosphorylated I-kappa-B kinase-β (IKκβ) Ser181/IKKβ and the expression of nuclear factor-kappa B (NF-κB) p65 protein were also increased. However, the treatment with BBR enhanced the glucose uptake, increased the expression of α7nAChR protein and inhibited AChE activity. These changes were also accompanied with the decrease of the ratio of pIKKβ Ser181/IKKβ, NF-κB p65 expression and IL-6 level. Taken together, these results suggest that BBR could enhance glucose uptake, and relieve insulin resistance and inflammation in HepG2 cells. The mechanism may be related to the cholinergic anti-inflammatory pathway and the inhibition of AChE activity.

Effects of berberine and cinnamic acid on palmitic acid-induced intracellular triglyceride accumulation in NIT-1 pancreatic β cells / 中国结合医学杂志

<p><b>OBJECTIVE</b>To investigate the effects of berberine (BBR) and cinnamic acid (CA), the main active components in Jiaotai Pill (, JTP), on palmitic acid (PA)-induced intracellular triglyceride (TG) accumulation in NIT-1 pancreatic β cells.</p><p><b>METHODS</b>Cells were incubated in culture medium containing PA (0.25 mmol/L) for 24 h. Then treatments with BBR (10 μmol/L), CA (100 μmol/L) and the combination of BBR and CA (BBR+CA) were performed respectively. Intracellular lipid accumulation was assessed by Oil Red O staining and TG content was measured by colorimetric assay. The expression of adenosine monophosphate-activated protein kinase (AMPK) protein and its downstream lipogenic and fatty acid oxidation genes, including fatty acid synthase (FAS), acetyl-coA carboxylase (ACC), phosphorylation acetyl-coA carboxylase (pACC), carnitine acyl transferase 1 (CPT-1) and sterol regulating element binding protein 1c (SREBP-1c) were determined by Western blot or real time polymerase chain reaction.</p><p><b>RESULTS</b>PA induced an obvious lipid accumulation and a significant increase in intracellular TG content in NIT-1 cells. PA also induced a remarkable decrease in AMPK protein expression and its downstream targets such as pACC and CPT-1. Meanwhile, AMPK downstream lipogenic genes including SREBP-1c mRNA, FAS and ACC protein expressions were increased. Treatments with BBR and BBR+CA, superior to CA, significantly reversed the above genes changes in NIT-1 pancreatic β cells. However, the synergistic effect of BBR and CA on intracellular TG content was not observed in the present study.</p><p><b>CONCLUSION</b>It can be concluded that in vitro, BBR and BBR+CA could inhibit PA-induced lipid accumulation by decreasing lipogenesis and increasing lipid oxidation in NIT-1 pancreatic β cells.</p>