ObjectiveTo construct an evaluation index system for the development of district-level disease prevention and control centers according to the requirements of the modernization of Shanghai’s disease control system and public health work practices， and to comprehensively assess the construction and development of district-level disease prevention and control institutions. MethodsAccording to the national and municipal requirements for the development of disease prevention and control institutions， an index framework was proposed through literature search and expert interviews. 39 representative experts in the field of public health at the national， provincial， and municipal （district） levels were selected to participate in the consultation and construction of the index system. The authority coefficient， the coefficient of variation， etc. were used to carry out quality control and determination of each index on the Delphi method. ResultsThe questionnaire response rate was 100%， the expert authority coefficient was 0.86，the degree of familiarity was 0.79， and the judgment basis was 0.92. The coefficients of variation of the necessary indicators in the index system were all <0.25 in the dimension of importance， and there were statistical differences in the statistical test of Kendall’s W coordination coefficients at all levels and dimensions （all P<0.001）. After multiple rounds of consultation， experts reached a consensus， forming a development evaluation index system of district-level CDCs with 6 first-level indicators， 24 second-level indicators， and 105 third-level indicators （including 63 necessary indicators and 42 recommended indicators）. ConclusionThe evaluation index system of Shanghai district-level CDCs based on the Delphi method has good authority， reliability， sensitivity and operability. This indicator system can effectively support the development of Shanghai district-level CDCs， and can be used for evaluation at multiple levels and in an all-round way in the future. The evaluation results can provide an evidence-based basis for the modernization of the disease prevention and control system and the continuous and dynamic updating of the development goals in the future.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

Glioblastoma (GBM) therapy is severely impaired by the blood-brain barrier (BBB) and invasive tumor growth in the central nervous system. To improve GBM therapy, we herein presented a dual-targeting nanotheranostic for second near-infrared (NIR-II) fluorescence imaging-guided photo-immunotherapy. Firstly, a NIR-Ⅱ fluorophore MRP bearing donor-acceptor-donor (D-A-D) backbone was synthesized. Then, the prodrug nanotheranostics were prepared by self-assembling MRP with a prodrug of JQ1 (JPC) and T7 ligand-modified PEG_5k-DSPE. T7 can cross the BBB for tumor-targeted delivery of JPC and MRP. JQ1 could be restored from JPC at the tumor site for suppressing interferon gamma-inducible programmed death ligand 1 expression in the tumor cells. MRP could generate NIR-II fluorescence to navigate 808 nm laser, induce a photothermal effect to trigger in-situ antigen release at the tumor site, and ultimately elicit antitumor immunogenicity. Photo-immunotherapy with JPC and MRP dual-loaded nanoparticles remarkably inhibited GBM tumor growth in vivo. The dual-targeting nanotheranostic might represent a novel nanoplatform for precise photo-immunotherapy of GBM.

Cancer immunotherapy is impaired by the intrinsic and adaptive immune resistance. Herein, a bispecific prodrug nanoparticle was engineered for circumventing immune evasion of the tumor cells by targeting multiple immune resistance mechanisms. A disulfide bond-linked bispecific prodrug of NLG919 and JQ1 (namely NJ) was synthesized and self-assembled into a prodrug nanoparticle, which was subsequently coated with a photosensitizer-modified and tumor acidity-activatable diblock copolymer PHP for tumor-specific delivery of NJ. Upon tumor accumulation via passive tumor targeting, the polymeric shell was detached for facilitating intracellular uptake of the bispecific prodrug. NJ was then activated inside the tumor cells for releasing JQ1 and NLG919 via glutathione-mediated cleavage of the disulfide bond. JQ1 is a bromodomain-containing protein 4 inhibitor for abolishing interferon gamma-triggered expression of programmed death ligand 1. In contrast, NLG919 suppresses indoleamine-2,3-dioxygenase 1-mediated tryptophan consumption in the tumor microenvironment, which thus restores robust antitumor immune responses. Photodynamic therapy (PDT) was performed to elicit antitumor immunogenicity by triggering immunogenic cell death of the tumor cells. The combination of PDT and the bispecific prodrug nanoparticle might represent a novel strategy for blockading multiple immune evasion pathways and improving cancer immunotherapy.

ObjectiveTo investigate the clinical effect of Shipiyin combined with diosmin in the treatment of lymphedema with spleen Yang deficiency syndrome（SYDS）after modified radical mastectomy and the specific effect on the function of the affected limb. MethodEighty-two patients with lymphedema with SYDS after modified radical mastectomy from outpatient and inpatient department of breast department and oncology department of the First Affiliated Hospital of Hunan University of Chinese Medicine were randomly divided into an observation group（41 cases） and a control group（41 cases）. The control group was given diosmin tablets（0.9 g per time， two times per day）on the basis of conventional treatment，and the observation group was given Shipiyin（one dose per day）on the basis of the control group. The course of treatment was 14 days. The clinical symptoms were observed and the limb circumference，traditional Chinese medicine（TCM） syndrome score，functional assessment of cancer therapy-breast cancer（FACT-B） score，disability of arm， shoulder and hand questionnaire（DASH） score，and joint range of motion were measured to analyze the TCM syndrome therapeutic effect and clinical efficacy. ResultAfter 14 days of treatment， the total effective rate of the observation group was 85.37% （35/41） and that of the control group was 63.41% （26/41） in the TCM symptoms， showing a statistically significant difference （Z=-2.212， P<0.05）. In terms of the clinical efficacy， the total effective rate in the observation group was 82.93% （34/41） and that in the control group was 75.61% （31/41）， indicating a statistically significant difference （Z=-2.061， P<0.05）. Compared with the situations before treatment， the scores of clinical symptoms such as the swelling of the upper limb， pain， sense of heaviness， stuffiness， fatigue， fullness， tightness， and skin keratosis and pruritus in the two groups were significantly lowered （P<0.01） after treatment. Compared with the control group， the observation group could better improve the swelling and fullness（P<0.01），as well as the feeling of pain，heaviness，stuffiness，fatigue，tightness，skin keratosis and pruritus （P<0.05）of the upper limbs of patients. The affected limb circumference， TCM syndrome score， and DASH score decreased significantly， while the FACT-B score and upper limb joint range of motion increased significantly in the two groups after treatment （P<0.01）. Compared with the control group， the observation group showed significantly reduced limb circumference at 10 cm proximal to the elbow striae， lowered TCM syndrome score， elevated FACT-B score（P<0.05）， decreased DASH score and improved range of motion of the upper limb joint （P<0.01） after treatment. ConclusionShipiyin combined with diosmin has better clinical efficacy in the treatment of lymphedema with SYDS after modified radical mastectomy than diosmin alone，which can better improve the clinical symptoms，signs，quality of life and limb functional activity of patients. This provides a new clinical program for the treatment of lymphedema after breast cancer surgery with integrated Chinese and western medicine.

Objective:To explore the new generation of intelligent ICU Unit based on 5G and artificial intelligence technology.Methods:This study was conducted at the Second Affiliated Hospital, Zhejiang University School of Medicine from May 2019 to August 2020. Based on a multidisciplinary team including medical, nursing, hospital management, clinical medical engineering, 5G technology, information technology, artificial intelligence technology, logistics service, etc, was assembled to intelligently design and reconstruct an intelligent ICU Unit of Emergency ICU.Results:Based on 5G technology, a new intelligent ICU unit environment was constructed to realize remote and high-speed interaction of multi-dimensional information in ICU, including intelligent assistance of remote monitoring, remote ward rounds, remote consultation and family visits. An intelligent hospital infection prevention and control system was established including automatic identification and alarm of hand hygiene and personal protection.Conclusions:The new generation of intelligent ICU unit combined with 5G and artificial intelligence technology has changed the mode of medical service for critically ill patients and improved the service level, which is worthy of further exploration and application.

Objective To analyze the influencing factors of affected renal function after laparoscopic nephron-sparing nephrectomy with segmental renal artery blocking (SRPN) for low R.E.N.A.L.score small localized renal tumor with follow-up data.Methods The data of 33 patients was collected,who underwent SRPN for small renal tumor from January 2010 to April 2012,and were followed-up for 5 years successfully.In 33 integrated data of 5-year follow-up,there were 14 males and 19 females,aged(56.5 ± 11.8)years.The preoperative affected renal glomerular filtration rate (aGFRpre),postoperative affected renal glomerular filtration rate (aGFRpost),the residual ratio of aGFR (aGFRpost/aGFRpre),preoperative affected renal volume (aVolpre),postoperative affected renal volume (aVolpost) and the residual ratio of aVol (aVolpost/aVolpre) were collected at the postoperative 3rd,6th,12th,24th and 60th month in follow-up period.Preoperative and postoperative data were analyzed by paired-sample T test.Multivariate linear regression analysis determined the influence of body mass index,operation time,localized warm ischemia time and distance from tumor to renal collecting system.Compare the correlation between aGFRpost/aGFRpre and aVolpost/aVolpre.Results All 33 cases were performed successfully.The mean operation time was (108.4 ± 9.1) min,and the mean time of segmental renal artery blocking was (23.3 ± 3.0) min.Postoperative pathologic 17 (51.5％) of clear cell carcinoma,5 (15.2％) of papillary carcinoma,3 (9.1％) of chromophobe cell carcinoma.All of above margins were negative.8 (24.2％) of angiomyolipoma (9.1％).All 33 cases were followed up for more than 5 years.The 5-year overoll survival (OS) and cancer specific survival (CSS) were 100％.In the 3rd,6th,12th,24th and 60th month,aGFRpost were (34.6 ± 4.6) ml/min,(34.7 ± 4.8) ml/min,(34.9 ± 4.4) ml/min,(35.1 ± 4.4) ml/min,(35.2 ± 4.2) ml/min,decreased of (10.4 ± 2.4) ml/min,(10.4 ± 2.6) ml/min,(10.1 ± 2.4) ml/min,(9.9 ± 2.4) ml/min,(9.8 ± 2.5) ml/min compared with aGFRpre (P ＜ 0.05).Multivariate linear regression analysis showed that body mass index,operation time,localized warm ischemia time in SRPN and distance from tumor to renal collecting system were unable to influence aGFRpost (P ＞ 0.05).The correlation coefficients between aGFRpost/aGFRpre and aVolpost/aVolpre were 0.659,0.667,0.663,0.629,0.604 respectively,and the difference was statistically significant (P ＜ 0.05).Conclusions For low R.E.N.A.L.score small localized renal tumor with SRPN,the decrease of postoperative affected renal function is relevant to postoperative affected renal volume,not as to operation time,localized warm ischemia time in SRPN and distance from tumor to renal collecting system.

Objective:To evaluate the meaning and value of high-frequency ultrasound in the diagnosis of carpal tunnel syndrome (CTS).Methods:In this study,48 patients (unilateral hand)with CTS were analyzed.The thickness of transverse carpal ligaments at the pisiform bone was measured using high-fre-quency ultrasound.Open carpal tunnel release procedure was performed in the 48 CTS patients,and the thickness of transverse carpal ligaments at the hamate hook bone measured using vernier caliper under di-rect vision.The accuracy of thickness of transverse carpal ligaments was evaluated using high-frequency ultrasound.High-frequency ultrasound measurement of thickness of transverse carpal ligaments at the ha-mate hook bone and pisiform bone,and determination of the diagnostic threshold measurement index using receiver operating characteristic (ROC)curve,sensitivity and specificity were performed and the correlation between the thickness of transverse carpal ligaments and nerve conduction study (NCS)ana-lyzed.Results:The thickness of transverse carpal ligaments in the CTS patients were (0.42 ±0.08)cm (high-frequency ultrasound)and (0.41 ±0.06)cm (operation)at hamate hook bone,and there was no significant difference between the two ways (t =0.672,P>0.05 ).The optimal cut-off value of the transverse carpal ligaments at hamate hook bone was 0.385 cm,the sensitivity 0.775,and the specificity 0.788.The optimal cut-off value of the transverse carpal ligaments at the pisiform bone was 0.315 cm, the sensitivity 0.950,and the specificity 1 .000.The transverse carpal ligaments thickness and wrist-in-
dex finger sensory nerve conduction velocity (SCV),wrist-middle finger SCV showed a negative correla-tion.Conclusion:High frequency ultrasound measurements of thickness of transverse carpal ligaments is a valuable method for the diagnosis of CTS.

Objective To comparatively investigate the characteristics of bone metabolism in forelimb malformation WHBE rabbits based on the OPG/RANK/RANKL system.Methods Healthy male 2-2.5-month old WHBE rabbit ( HWR) , Healthy Japanese rabbit ( HJR) and forelimb malformation WHBE rabbit ( FMWR) were used in this study and divided into 3 groups, HWR, HJR and FMWR groups, with 10 rabbits in each group.The shape of forelimb and mean gray value observed from X-ray film were examined, and the bone tissue micro-morphology was analyzed using HE staining.Re-al-time fluorescence quantitative PCR was used to determine the expression of osteoprotegerin ( OPG) and receptor activator of NF-KB ligand ( RANKL) mRNA.The expressions of OPG, receptor activator of NF-KB ( RANK) and RANKL protein in serum and bone tissue were assayed by enzyme-linked immunoassay ( ELISA) and immunohistochemistry, respectively. Results Compared with the HWR and HJR groups, rabbits in the FMWR group appeared abnormal in toutuous forelimb and thinner bone cortex.The mean gray values of X-ray in the FMWR group were lower than that in the HWR group ( P<0.05).There were significant differences between the FMWR and healthy rabbits (HWR and HJR) in the following pa-rameters:RANKL mRNA expression and RANKL/OPG mRNA ratio in the liver(P<0.05, P<0.01), serum protein expression of RANK and RANKL and RANKL/OPG ratio (P<0.05, P<0.01), and positive index of expression of RANKL protein and RANKL/OPG ratio in the bone tissue(P<0.05, P<0.01).Furthermore, the gene expression lev-els of OPG and RANKL of HWR were significantly higher than that of HJR(P<0.05, P<0.01).Conclusions The FMWR show some abnormal symptoms in bone metabolism as well as decrease of bone quality and histological changes of bone micro-structure, due to the significant increase of RANKL/OPG ratio of FMWR.The breed differences between WHBE and Japanese rabbits in RANKL mRNA expression level may be one of factors inducing limb malformation in the WHBE rabbits.

Objective To investigate the Laparoscopic management for Nutcraker Syndrome(NCS) with resection of fibrous ring and placing extravascular stent.Methods This was a retrospective analysis of clinical data and treatment process of cases from March 2010 to February 2015 in urology department,affiliated hospital of Guizhou medical university.Five cases with NCS,4 males and 1 female;age were 28-40 years,mean age was 35 years,all cases were afflicted with gross hematuria and flank pain,the history of gross hematuria were 6-72 months.3 cases were afflicted with proteinuria.Duplex ultrasound scanning before surgery revealed the compressed left renal vein (LRV) between the aorta and the superior mesenteric artery(SMA),with peak velocity 110-132 cm/s,an average of 121 cm/s.The flow velocity of LRV in the renal hilum were 18-25 cm/s,an average of 21 cm/s.CT scanning showed that the stricture segment diameter of LRV were 1.2-2.5 mm,an average of 1.8 mm;and the max diameter of proximal dilatation of the LRV in renal hilum were 8.3-15.2 mm,an average of 10.1 mm.The ratio between the dilated segment inner diameter and the stricture segment were 3.4-9.5.Bleeding from the left ureteral orifice was detected by cystoscopy in 3 cases.5 cases were treated by resection of fibrous ring and placing extravascular stent with Laparoscopic management,and the average length of extravascular stent was 4.0 cm.Results The operation was successful in the 5 cases.The average operation time was 83 min.The average blood loss was 65 ml.Hematuria gradually reduce 5-6 days and resolved 7-20 days after surgery in 5 patients.Proteinuria was disappeared successful 2 weeks after surgery in 3 patients.There was no recurrence at 8-24 months' follow-up.3 days after surgery Doppler ultrasound showed the stricture segment diameter of LRV were 3.8-5.6 mm,an average of 4.9 mm;the ratio between the dilated segment inner diameter and the stricture segment decreased were 1.1-2.0,an average of 1.6;the peak velocity of compressed LRV were 25-45 cm/s,an average of 34 cm/s.6 months after surgery,CTA result showed no LRV compression in the aortomesenteric region;the max diameter of LRV in renal hilum were 7.9-9.8 mm and 6.0-8.8 mm in the aortomesenteric region of LRV.Conclusion Etiology of NCS exist a fibrous ring around the left renal vein outflow of the inferior vena cava besides the commonly anatomic extrinsic compression on the LRV as it crosses between the superior mesenteric artery and the aorta.The Laparoscopic management for NCS with resection of fibrous ring and placing extravascular stent is an effective minimally invasive treatment.