The S1P1 regulator IMMH002 and its therapeutic effect and mechanism on autoimmune hepatitis / 药学学报

This study assessed and explored the pharmacological effects and mechanisms of action of IMMH002 {2-amino-2-(2-(4ʹ-(2-ethyloxazol-4-yl)-[1,1ʹ-biphenyl]-4-yl)ethyl)propane-1,3-dio}, a selective sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator, in a concanavalin A (ConA)-induced autoimmune hepatitis (AIH) mouse model. The experimental protocol strictly adhered to the guidelines of the Ethics Committee for Animal Research of the Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College (Approval No.: 00004046). Male ICR mice were pre-treated with the drug for four days, followed by induction of AIH through tail vein injection of ConA protein. Liver function, hepatic tissue pathology, peripheral blood parameters, as well as immunoglobulin G (IgG), inflammatory cytokines, T cell distribution, and inflammatory pathways were evaluated in mice. Results demonstrated that IMMH002 significantly reduced liver function indicators such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), alleviated hepatic tissue inflammation and necrotic damage, decreased serum IgG levels, and lowered the expression of inflammatory mediators including interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and interferon γ (IFN-γ). Additionally, it facilitated T lymphocyte homing, downregulated the phosphorylation of nuclear factor kappa-B (NF-κB), IκB kinase β (IKKβ) and nuclear factor inhibitor protein-α (IκBα) proteins in hepatic tissue and cellular inflammation models. Collectively, IMMH002 effectively ameliorated ConA-induced autoimmune hepatitis in mice, exhibiting extensive anti-inflammatory and anti-necrotic effects, thereby laying a theoretical foundation for AIH clinical treatment.

Mechanism of Bushen Huatan Prescription in Regulation of Osteogenesis and Adipogenic Differentiation and Improvement of Postmenopausal Bone Loss in Ovariectomized Rats with Osteoporosis / 中国实验方剂学杂志

ObjectiveTo explore the underlying mechanism of Bushen Huatan prescription in alleviating postmenopausal osteoporosis （PMOP） by maintaining the balance of osteogenesis and adipogenic differentiation in ovariectomized rats with osteoporosis. MethodSeventy-five 6-month-old non-pregnant female SD rats were randomly divided into sham-operation group， model group， atorvastatin group， liviol group， and Bushen Huatan prescription group. Bilateral ovaries were removed in the four groups except the sham-operation group， while only the same mass of adipose tissue around the ovaries was removed in the sham-operation group. On the 5th week after surgery， drugs were consecutively administrated for 8 weeks. Rats in the Bushen Huatan prescription group received 9.4 mg·kg-1 of the prescription， rats in the atorvastatin group received 0.92 mg·kg-1 of atorvastatin， rats in the Liviol group received 0.23 mg·kg-1 of liviol， and rats in the model group and the sham-operation group received saline once a day. Micro-computed tomography （Micro CT） was used to detect bone mineral density （BMD） of rat tibia in each group. Hematoxylin-eosin （HE） staining was used to detect the relative area of rat bone marrow adipose tissue （BMAT） in each group. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the relative expression levels of Runt-related transcription factor 2 （Runx2）， peroxisome proliferator-activated receptor （PPARγ）， leptin （LPN）， and leptin receptor （OBR） in bone tissues. ResultAs compared with the sham operation group， the BMD of rats in the model group decreased （P<0.05）， while the relative area of BMAT increased （P<0.05）. In addition， the expression levels of LPN， OBR， and Runx2 decreased in the model group （P<0.05）， while the level of PPARγ increased （P<0.05）. As compared with the model group， the BMD of rats in the atorvastatin group， the Livial group， and the Bushen Huatan prescription group increased （P<0.05）， and the relative area of BMAT decreased （P<0.05）. The expression levels of LPN， OBR， and Runx2 in these groups increased （P<0.05）， while the expression level of PPARγ decreased （P<0.05）. ConclusionBushen Huatan prescription plays the anti-osteoporosis role in the rat model of PMOP through up-regulating LPN and OBR in bone tissues and maintaining the balance of osteogenesis and adipogenic differentiation， thereby reducing postmenopausal bone loss and playing a role in the prevention and treatment of PMOP.

Retrospective analysis on 77 cases of T4b hypopharyngeal carcinoma treated by non-surgical treatments / 中华耳鼻咽喉头颈外科杂志

Objective: To analyze the effectiveness, safety and factors influencing the clinical prognosis of patients with hypopharyngeal carcinoma in T4b by nonsurgical treatments. Methods: The clinical data of 77 patients with T4b hypopharyngeal cancer treated in the College of Otolaryngology Head and Neck Surgery of the Chinese People's Liberation Army General Hospital from January 2010 to June 2021 were analyzed retrospectively. All were males, aged(57.0±8.0)years old. Patients were treated with induction chemotherapy plus concurrent chemoradiotherapy. Kaplan Meier survival analysis was used to compare the effects of different factors on prognosis. Adverse reactions during treatments and the causes of death were analyzed. Results: 98.7% of 77 patients with T4b hypopharyngeal cancer completed the chemotherapy plan and 94.8% completed the radiotherapy plan. The most common adverse reactions were grade 2 radiation oral mucositis (50/77, 64.9%) and grade 2 leukopenia (50/77, 64.9%). The incidence of grade 3 severe hoarseness was 7.8% (6/77), one patient (1.3%) underwent gastrostomy due to dysphagia, and pronunciation and swallowing function were effectively preserved in other patients. The overall survival rate was 71.9% at 1 year, 45.6% at 3 years and 29.7% at 5 years. The location of tumor, the presence of liquefaction necrosis in tumor, the use of molecular targeted drugs and the approach of radiotherapy were independent factors,each of which that affected the prognosis of T4b patients with advanced hypopharyngeal cancer [HR (95%CI) were 1.867(1.085-3.213), 3.018 (1.437-6.335), 0.372 (0.181-0.764) and 2.158 (1.015-4.588), respectively, P<0.05]. The two leading causes of death with high incidence were disease recurrence (12/32, 37.5%) and cervical large vessel rupture and hemorrhage (11/32, 34.4%). Conclusions: Non-surgical comprehensive treatment offers a high laryngeal preservation rate in patients with T4b hypopharyngeal cancer. The location of tumor, the liquefaction necrosis within tumor, the use of molecular targeted drugs, and the approach of radiotherapy are independent prognostic factors.

Application of augmented reality and mixed reality navigation technology in laparoscopic limited right hepatectomy / 中华外科杂志

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.

Mechanism of Bushen Huatan Prescription in Regulating Th17/Treg Balance in Ovariectomized Osteoporosis Rats / 中国实验方剂学杂志

Objective:To study the effect of Bushen Huatan prescription on helper T cell 17 （Th17）/T regulatory cells （Treg） balance of immune T cell subsets in the prevention and treatment of postmenopausal osteoporosis. Method:Sixty 6-month-old female SD rats were randomly divided into sham operation group， model group， estradiol valerate group （0.184 mg·kg^-1） and Bushen Huatan prescription low， medium and high groups （4.7， 9.4， 18.8 g·kg^-1） according to the random number table. All the groups except the sham operation group received ovariectomy to make postmenopausal osteoporosis model. Intragastric administration was started 1 week after operation， and the rats in model group and sham operation group received equal volume of normal saline， once a day for 12 weeks. Microcomputed tomography （Micro CT） was then used to detect bone mass and microstructure of rats， the contents of Forkhead box protein （Foxp3） and retinoic acid related nuclear orphan receptor （ROR<italic>γ</italic>t） in serum were detected by enzyme-linked immunosorbent assay （ELISA）， the mRNA expression levels of Foxp3 and ROR<italic>γ</italic>t in bone tissues were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot was used to detect the protein expression of Foxp3 and ROR<italic>γ</italic>t in bone tissues， the number of Th17 and Treg cells in each group was analyzed and compared by flow cytometry. Result:Compared with the sham operation group， the bone mass and trabeculae of the model group decreased （<italic>P</italic><0.01）， the bone microstructure was destroyed， the concentration of Foxp3 in serum decreased， the concentration of ROR<italic>γ</italic>t increased （<italic>P</italic><0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues decreased， ROR<italic>γ</italic>t increased， the number of Treg cells in bone tissues decreased， number of Th17 cells increased （<italic>P</italic><0.01）， and Th17/Treg ratio increased （<italic>P</italic><0.01） in model group. Compared with the model group， the bone mass in each treatment group increased （<italic>P</italic><0.05， <italic>P</italic><0.01）， Foxp3 concentration in serum increased， ROR<italic>γ</italic>t concentration decreased （<italic>P</italic><0.01）， the mRNA and protein expression levels of Foxp3 in bone tissues increased significantly （<italic>P</italic><0.05， <italic>P</italic><0.01）， but no statistical difference was shown in mRNA expression between low dose group and the model group. In addition， the mRNA and protein expression of ROR<italic>γ</italic>t decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， number of Treg cells increased， number of Th17 cells decreased （<italic>P</italic><0.05， <italic>P</italic><0.01）， and Th17/Treg ratio decreased in treatment groups （<italic>P</italic><0.01）. Conclusion:Bushen Huatan prescription can increase bone mass， improve bone microstructure， increase the number of Treg cells and decrease the number of Th17 cells in ovariectomized rats. It is concluded that Bushen Huatan prescription may play a role in preventing and treating postmenopausal osteoporosis by regulating Th17/Treg balance.

Effect of Bushen Huatan Prescription on Serum LPS and TLR4/MyD88/NF-κB Signaling Pathway in Rats with Ovariectomy-induced Osteoporosis / 中国实验方剂学杂志

Objective:To explore the effect of Bushen Huatan prescription on serum lipopolysaccharide （LPS） and Toll-like receptor 4 （TLR4）/ myeloid cell differentiation protein 88 （MyD88）/nuclear transcription factor-<italic>κ</italic>B （NF-<italic>κ</italic>B） signaling pathway in rats with ovariectomy-induced osteoporosis. Method:Sixty SPF 6-month-old female rats were randomly divided into sham operation group， model group， estradiol valerate group and Bushen Huatan prescription low， medium and high dose groups.One week after modeling by bilateral ovariectomy， 8 rats in each group were selected to receive intragastric administration.The estradiol valerate group was given 0.184 mg·kg^-1 by gavage， and Bushen Huatan prescription low， middle and high dose groups were given 4.7， 9.4 and 18.8 g·kg^-1 by gavage， sham operation group and model group were given 0.9% saline 4 mL by gavage respectively.After 12 weeks of intervention， the rats were sacrificed for detection.Serum LPS was detected by enzyme linked immunosorbent assay （ELISA）， while protein expressions of TLR4， MyD88 and phosphorylated （p）-NF-<italic>κ</italic>B p65 in bone tissue were detected by Western blot， and the mRNA expressions of TLR4， MyD88， NF-<italic>κ</italic>B p65， IL-1<italic>β</italic>， and IL-6 in bone tissue were detected by quantitative real-time polymerase chain reaction（PCR）. Result:Compared with sham operation group， the serum LPS level as well as protein expression of TLR4， MyD88， p-NF-<italic>κ</italic>B p65 and mRNA expression of TLR4， MyD88， NF-<italic>κ</italic>B p65， IL-1<italic>β</italic>， and IL-6 significantly increased in model group（<italic>P</italic><0.05）.Compared with the model group， serum LPS level， protein expression of TLR4， MyD88， and p-NF-<italic>κ</italic>B p65， mRNA levels of TLR4， MyD88， and NF-<italic>κ</italic>B p65 in bone tissues as well as downstream inflammatory factors IL-1<italic>β</italic>， IL-6 mRNA expression decreased to different degrees in estradiol valerate group and Bushen Huatan prescription high dose group（<italic>P</italic><0.05）. Conclusion:Bushen Huatan prescription can reduce serum LPS content， regulate mRNA and protein expression of TLR4， MyD88， NF-<italic>κ</italic>B p65 and p-NF-<italic>κ</italic>B p65 in TLR4/MyD88/NF-<italic>κ</italic>B pathway， and down-regulate mRNA levels of IL-1<italic>β</italic> and IL-6 in bone tissues to improve bone microstructure and inhibit the development of postmenopausal osteoporosis （PMOP）.

Effect of FcRn on in vivo pharmacokinetics of a novel monoclonal antibody against West Nile virus MIL94 / 中国药理学通报

Aim To investigate the effects of different species Fc receptors (FcRn) on pharmacokinetic characteristics of MIL94, a monoclonal antibody against West Nile virus developed by Academy of Military Sciences, which has a neutralizing effect on West Nile virus and whose maintenance time in vivo is closely related to its antiviral effect. Methods The pharmacokinetic characteristics of MIL94 in mice expressing FcRn of different species (wild-type mice, hFcRn mice and FcRn knockout mice) were compared-. Wild-type mice and FcRn knockout mice were injected intravenously with MIL94 respectively. HFcRn mice were randomly divided into four groups. Two groups were injected intravenously with MIL94, and the other two groups were injected intravenously with intravenous immunoglobulin (IVIG) and then intravenously with MIL94. Indirect ELISA was used to determine the MIL94 concentration in mouse serum. WinNonlin software was used to calculate the pharmacokinetic parameters. Results After intravenous injection with MIL94, the in vivo pharmacokinetics were basically linear. The distribution volume of MIL94 in animals was related to FcRn. The half-life in vivo varied greatly between different groups. Conclusions FcRn can affect the half-life of MIL94 in different species mainly via alternation of its elimination and distribution. It is expected that the half-life of FcRn in human will be longer than that in preclinical animals.

Metabolomics study on anti-PTSD effect of novel ligand TSPO compound YL-IPA08 on plasma metabolic spectrum of PTSD model rats / 中国药理学通报

Aim To investigate the effects of YL- IPA08 on the endogenous metabolites of PTSD model rats by metabolomics methods, and to explore the metabolic pathways and possible mechanisms of YL-IPA08 against PTSD. Methods The rats were randomly divided into control group, PTSD model group, and administration group of PTSD rats induced by forced swimming test, and the treatment group was given YL- IPA08 (2 mg • kg"1) by intragastric gavage for 15 consecutive days. High-performance liquid chromatog- raphy-mass spectrometry (HPLC-MS/MS) technology was used to detect the endogenous differential metabolites and the associated metabolic pathways in rat plasma samples. Targeted quantitative technology was simultaneously applied to detect the concentrations of 18 bile acids in rat plasma. Results Compared with control group, 40 kinds of endogenous metabolites including glutamic acid, proline, valine, arginine, leucine , cholic acid, and creatine showed significant difference, and the concentrations of 11 bile acids significantly increased in plasma of model group as well. Compared with model group, after YL-IPA08 intervention , the above-mentioned potential metabolites ap-peared to return to normal levels. Conclusions Metabolomics analysis reveals that YL-IPA08 has intervention effect on PTSD model rats. The mechanism may be related to the regulation of amino acid metabolism and bile acid metabolism.

Application of 3D visualization and 3D printing in individualized precision surgery for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma / 南方医科大学学报

OBJECTIVE@#To explore the application of 3D visualization and 3D printing in individualized precision surgical treatment of Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma.@*METHODS@#We retrospectively analyzed the data of 10 patients with hilar cholangiocarcinoma undergoing surgeries under the guidance of 3D visualization and 3D printing in the Department of Hepatobiliary Surgery, Zhujiang Hospital from May 2016 to March 2019. Thin-section CT data of the patients were collected for 3D reconstruction and 3D printing, and the 3D printed models were used for observing the 3D relationship of tumor with the intrahepatic bile duct, hepatic artery, portal vein and hepatic vein system and for performing preoperative simulated surgery and surgical planning. The 3D printed models were subsequently used for real-time intraoperative navigation to guide surgeries in the operating room.@*RESULTS@#3D visualization models were successfully reconstructed for all the 10 patients and printed into 3D models. The 3D visualization types in Bismuth-Corlette classification included type Ⅲa (4 cases), type Ⅲb (4 cases), and type Ⅳ (2 cases); 4 patients showed portal vein variation, 3 had hepatic artery variation, and 2 had both portal vein and hepatic artery variations. Two patients were found to have trifurcation type of portal vein variation, one had "I-shaped" variation, and one showed the absence of the right anterior branch of the portal vein; 3 patients had hepatic artery variations with the left hepatic artery originating from the left gastric artery (1 case) and the right hepatic artery originating from the superior mesenteric artery (2 cases). Four patients with type Ⅲb underwent left hepatectomy; 4 with type Ⅲa received right hepatectomy; 1 patient with of type Ⅳ received peripheral hepatic resection and another underwent left hepatectomy. The results of preoperative 3D reconstruction, 3D printed model and preoperative planning were consistent with the intraoperative findings. The operative time was 452±75.12 min with a mean intraoperative blood loss of 356±62.35 mL and a mean hospital stay of 15 ± 4.61 days in these cases. One patient had bile leakage and 3 patients had pleural effusion postoperatively, and they were discharged after drainage and medications. No liver failure or death occurred in these cases perioperatively.@*CONCLUSIONS@#3D visualization and 3D printing can facilitate accurate preoperative assessment, surgical planning and surgical procedure optimization for Bismuth-Corlette type Ⅲ and Ⅳ hilar cholangiocarcinoma to improve surgical safety and reduce surgical risks especially in cases of intrahepatic vascular variations.

Clinical efficacy of three-dimensional visualization technique combined with enhanced recovery after surgery in the treatment of hepatolithiasis / 中华消化外科杂志

Objective To investigate the clinical efficacy of three-dimensional visualization technique (3DVT) combined with enhanced recovery after surgery (ERAS) in the treatment of hepatolithiasis.Methods The retrospective cohort study was conducted.The clinicopathological data of 64 patients with hepatolithiasis who were admitted to Zhujiang Hospital of Southern Medical University from November 2015 to August 2018 were collected.There were 17 males and 47 females,aged from 30 to 82 years,with a median age of 55 years.Of the 64 patients,23 who completed preoperative assessment and planning using 3DVT,and furthermore received ERAS for perioperative management were divided into 3DVT + ERAS group,and 41 who received preoperative assessment merely under the guidance of 3DVT,combined with conventional perioperative management were divided into 3DVT + conventional group.Observation indicators:(1) preoperative CT and 3DVT assessment;(2) perioperative conditions;(3) follow-up.The follow-up was conducted by outpatient service,e-mail or telephone interview to detect the postoperative recurrence of hepatolithiasis up to March 2019.The measurement data with normal distribution were expressed as Mean±SD,and the t test was used for comparison between groups.The measurement data with skewed distribution were expressed as M (P25,P75),and the Mann-Whitney U test was used for comparison between groups.The count data were expressed as absolute numbers or percentages,and the comparison between groups was pedormed using the chi-square test or Fisher exact probability.Results (1) Preoperative CT and 3DVT assessment:23 patients in the 3DVT + ERAS group underwent preoperative CT examination and 3DVT assessment,the consistency between CT results and intraoperative findings was 91.3％ (21/23),and the consistency between 3DVT results and intraoperative findings was 95.7％(22/23).Fourty-one patients in the 3DVT + conventional group underwent preoperative CT examination and 3DVT assessment,the consistency between CT results and intraoperative findings was 90.2％ (37/41),and the consistency between 3DVT results and intraoperative findings was 95.1％ (39/41).(2) Perioperative conditions:the volume of intraoperative blood loss,duration of postoperative hospital stay,postoperative total bilirubin,postoperative direct bilirubin,postoperative albumin,postoperative alanine aminotransferase,postoperative aspartate aminotransferase and postoperative hemoglobin were 50 mL (10 mL,100 mL),8 days (7 days,9 days),12 μmol/L (9 μmol/L,16 μmoL/L),6 μmol/L (4 μmoL/L,8 μmol/L),(37±4)g/L,44 U/L (18 U/L,85 U/L),32 U/L (20 U/L,65 U/L),(117±18)g/L in the 3DVT + ERAS group,and 100 mL (50 mL,300 mL),13 days (10 days,16 days),17 μmol/L (12 μmoL/L,33 μmoL/L),11 μmoL/L (7 μmoL/L,21 μmol/L),(29±6)g/L,78 U/L (43 U/L,122 U/L),121 U/L (72 U/L,176 U/L),(106±13)g/L in the 3DVT + conventional group,respectively;there were significant differences between two groups (Z =-3.084,-4.827,-2.953,-3.632,t =5.261,Z=-2.960,-4.625,t =2.773,P＜0.05).Two patients had pulmonary infection and 2 had pleural effusion in the 3DVT + ERAS group,and all the 4 patients were cured after treatment.One case of biliary fistula,4 cases of pulmonary infection and 5 cases of pleural effusion occurred in the 3DVT + conventional group,and these patients were cured by adequate abdominal drainage,antibiotic therapy and thoracocentesis,respectively.There was no perioperative death in either group.(3) Follow-up:64 patients were followed up for 6-36 months,with a median time of 23 months.During the follow-up,no recurrent hepatolithiasis in the 3DVT + ERAS group,and 1 case of recurrent hepatolithiasis was confirmed by ultrasound in the 3DVT + conventional group.No cholangiocarcinoma occurred in either group.Conclusion The combination of 3DVT and ERAS is effective,safe and feasible in the management of hepatolithiasis,which can accelerate the postoperative recovery of liver function,thus enhancing perioperative recovery and improving the prognosis of patients simultaneously.

Application value of multimodal image fusion technology in the diagnosis and treatment of intrahepatic cholangiocarcinoma / 中华消化外科杂志

Objective To explore the application value of multimodal image fusion technology in the diagnosis and treatment of intrahepatic cholangiocarcinoma (ICC).Methods The retrospective descriptive study was conducted.The clinicopathological data of 11 patients with ICC who were admitted to Zhujiang Hospital of Southern Medical University between January and September 2018 were collected.There were 5 males and 6 females,aged (55 ± 12)years,with a range from 30 to 74 years.The data of contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI) with gadoxetate disodium (Gd-EOB-DTPA) of the upper abdomen were respectively collected,and three-dimensional(3D) model of liver was constructed based on CT-MRI fusion images.The preoperative evaluation and surgical planning were carried out based on the different modal imaging examination technologies.The indocyanine green (ICG) molecular fluorescence imaging system and augmented reality navigation system were used to guide hepatectomy.Observation indicators:(1) preoperative evaluation;(2) intraoperative situations;(3) comparison between surgical planning based on the different model imaging technologies and actual surgical method;(4) follow-up.Follow-up using outpatient examination and telephone interview was performed to detect postoperative complications up to November 2018.Measurement data with normal distribution were represented as Mean ± SD,measurement data with skewed distribution were represented as M (range).Count data were described as absolute number or percentage and comparisons were analyzed using the paired chi-square test.Results (1) Preoperative evaluation:the proportions of grade 3 and above branch vessels of the portal vein and hepatic vein system and tumor margin by enhanced CT examination and enhanced MRI examination were respectively 11/11,4/11 and 5/11,11/11,with statistically significant differences in above indicators (x2 =4.16,5.14,P＜0.05).The enhanced CT showed 11 liver cancer lesions and enhanced MRI showed 13 lesions (including 2 lesions not demonstrated by enhanced CT,with a maximum diameter ≤ 10 mm).The 3D model of liver based on CT-MRI fusion image:location,number,infiltrating range (tumor boundary),intrahepatic vascular distribution,variation and its spatial relationship with lesions could be stereoscopically,intuitively and comprehensively displayed.(2) Intraoperative situations:of 11 patients,11 lesions were explored with naked eyes;13 lesions were detected by ICG molecular fluorescence imaging system,including 2 lesions showing low uptake lesions in liver and gallbladder specific period by preoperative MRI examinations and intrahepatic metastasis cancer by pathologic examination.Of 11 patients,6 had naked-eye ischemia boundaries around related vessels of hepatic portal ligation;10 with anatomical hepatectomy had hepatic segments or hemihepatic boundary by ICG molecular fluorescence imaging system,including 2 using positive staining and 8 using anti-staining.Among 11 patients,3 (1 combined with local resection of hepatic segment Ⅷ metastases),2,2,1,1,1 and 1 underwent respectively left hepatectomy,left lateral lobectomy of liver,right hepatectomy,extended right hepatectomy,right lobectomy of liver,resection of partial hepatic segment Ⅷ and mesohepatectomy.Seven of 11 patients received regional lymph node dissection and 4 received simple lymph node biopsy.Of 11 patients,1 diagnosed as with bile leakage of liver section underwent suture and ligation treatment with 4-0 Prolene;10 didn't occurred bile leakage.The surgical margin of 11 patients was negative.The operation time,volume of intraoperative blood loss and duration of hospital stay were (240± 118)minutes,(275±249)mL and (13 ± 8) days,respectively.There was no blood transfusion in the perioperative period.(3) Comparison between surgical planning based on the different model imaging technologies and actual surgical method:surgical planning of 3D model based on CT,MRI and CT-MRI fusion image in 6,9 and 11 patients was respectively consistent with actual surgical method.(4) Follow-up:11 patients were followed up for 2-10 months,with a median time of 6 months.Three patients had postoperative complications,2 of which were found in Clavien-Dindo Ⅰ and Ⅱ,including 1 with pleural effusion + peritoneal effusion and 1 with pleural effusion,they were improved after conservative treatment;1 with complication of Clavien-Dindo Ⅲ (postoperative intra-abdominal bleeding) was improved by selective arterial embolization using percutaneous femoral artery puncture.There was no postoperative bile leakage,hepatic failure and death.Conclusion Multimodal image fusion technique is helpful to optimize the preoperative surgical planning,which can assist the recognition of important vessels and real-time navigation of hepatectomy during operation,and improve the safety of operation.

Ideas for New Drug Discovery of Prevention and Treatment of Diabetic Nephropathy Based on “Holistic View” in Tibetan Medicine / 中国实验方剂学杂志

Diabetic nephropathy(DN) is a kind of severe diabetes mellitus(DM) complications,which is one of the most common cause of end-stage renal failure.The incidence of DN increases with the increase of the number of DM patients,and early prevention is the key.DM and DN are characteristic advantages of Tibetan medicine,the "holistic view" of dynamic balance based on the three major factors in the body(Sanyin,included rlung,mkhris-pa and bad-gan) is a unique understanding of DM and DN among Tibetan medical practitioners,and which has rich and unique clinical and medication experiences in DN treatment.This paper discussed the medical theory "holistic view" on the Tibetan medicine for DM and DN,dug commonly used Tibetan drugs and Tibetan medical prescriptions for clinical treatment of DN,in order to provide new ideas for the treatment of DN and the discovery of new drugs for DN, and give full play to the unique advantages of Tibetan medicine.

Three-dimensional visual assessment and virtual reality study of centrally located hepatocellular carcinoma on the axis of blood vessels / 中华外科杂志

Objective@#To explore a novel method for preoperative precision assessment of centrally located hepatocellular carcinoma(HCC) with blood vessel as axis based on three-dimensional(3D) visualization and virtual reality(VR) technology and its application values.@*Methods@#High-quality thin-layer enhanced CT data were collected from 20 patients with centrally located HCC who treated at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from March 2017 to August 2018 diagnosed by preoperative examination. There were 18 males and 2 females, aged 28 to 69 years, all of Child-Pugh grade A. First of all, 3D reconstruction was performed by a 3D visualization software; then, the reconstructed 3D image was imported into VR development engine for VR research; afterwards, the analysis and evaluation system with blood vessel as axis was established based on 3D visualization classification of centrally located HCC; therefore, the relationship of the tumor to its major peripheral blood vessels was accurately judged and the surgical planning was formulated. Two images were brought into the operating room for navigation in surgery. The assessments results of preoperative data (CT and (or) MRI) and three-dimensional visualization of blood vessels in VR environment were compared; the values of the preoperative and postoperative hemoglobin, serum albumin and bilirubin were recorded and compared. Chi-square test, t-test and non-parametric test were used for the analysis of counting data, continuous measurement data and non-normal distribution measurement data, respectively.@*Results@#3D visualization modeling was completed in all of the 20 patients with centrally located HCC. According to the results of 3D visualization classification of centrally located HCC, there were 3 cases of type Ⅰ,1 case of type Ⅱ,4 cases of type Ⅲ,7 cases of type Ⅳ and 5 cases of type Ⅴ; according to the assessment and classification based on blood vessel as the axis, there were 6 cases of type Ⅰa,2 cases of type Ⅰb,2 cases of type Ⅱa,9 cases of type Ⅱb and 1 case of type Ⅱc. All patients underwent successful resection of tumor under the guidance of 3D visualization and VR technology. There were 15 cases whose assessment results based on preoperative CT/MRI were consistent with intraoperative findings, with a coincidence rate of 75.0%(15/20); while in VR environment, the assessment results of 3D visualization with blood vessel as axis were all consistent with the intraoperative findings, with coincidence rate of 100%(20/20). There was a statistically significant difference between the groups (χ2=5.714, P=0.017). There was no red blood cell transfusion in all patients during the operation. The preoperative hemoglobin was (128.8±14.9)g/L, and it was (119.8±12.5)g/L on postoperative day 1. There was no significant difference between these two sets of data (t=2.07, P=0.054). No death during the perioperative period and no complications such as hepatic failure, hemorrhage and biliary fistula after operation occurred.@*Conclusion@#Preoperative evaluation based on 3D visualization and VR technology with blood vessel as the axis has significant clinical value for preoperative planning and surgical navigation of centrally located HCC.

Optimization of Purification Process of Total Alkaloid Extract of Berberis dictyophylla Cortex by Macroporous Resin and Investigation of Its Quality Standard / 中国实验方剂学杂志

Objective: To optimize purification process of total alkaloid extract of Berberis dictyophylla cortex by macroporous resin,and to establish its quality standard. Method: Acid dye colorimetry was used to investigate the purification process of total alkaloid extract of B. dictyophylla cortex,the process parameters included concentration of sample solution,speed of sampling,diameter-height ratio of resin column,water washing amount,concentration and dosage of eluent,flow rate of elution,etc.In order to determine the optimum process,HPLC was employed to determine the contents of four alkaloids(magnoflorine,jatrorrhizine hydrochloride,palmatine hydrochloride,and berberine hydrochloride) with mobile phase of acetonitrile-0.1% phosphoric acid aqueous solution for gradient elution and detection wavelength at 270 nm.After being purified,quality standard of total alkaloid extract of B. dictyophylla cortex was investigated according to the requirements in the 2015 edition of Chinese Pharmacopoeia. Result: Optimal purification conditions were as following:10 g of HPD100 macroporous adsorption resin with a column diameter-height ratio of 1:8,sampling solution concentration of 11 g·L-1,the loading flow rate of 1 mL·min-1,sampling solution volume of 50 mL,washed with 4 BV of water(1 BV=15 mL) and added 9 BV of 30% ethanol,after being purified,the transfer rate of total alkaloids was>80%,and its purity was>65%.The quality standard of total alkaloid extract of B. dictyophylla cortex was established,there were 19 common peaks in the characteristic chromatogram,and the overall similarity was>0.99. Conclusion: This optimized purification process is stable and feasible, and the established quality standard is controllable.

Effect of Berbamine Hydrochloride on Intestinal Absorption Characteristics of Berberine Hydrochloride by Rat Everted Intestinal Sac Model / 中国实验方剂学杂志

Objective: To investigate the effect of berbamine hydrochloride on the absorption characteristics of berberine hydrochloride in different intestinal segments of rats in normal environment and high calcium environment. Method: Taking rat everted intestinal sac model,the content of berberine hydrochloride in absorbent solution of everted intestinal sac from different compatibility groups was determined by HPLC,and the uptake per unit area in different groups was analyzed by One-way ANOVA. Result: Compared with the normal J70 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L-1) at the same time point,the uptake per unit area of the normal J70+Ver100 group(in normal environment,the concentration of berberine hydrochloride was 70 mg·L-1,adding verapamil hydrochloride to a concentration of 100 mg·L-1) was significantly increased in the ileum(P-1,adding berbamine hydrochloride to a concentration of 35 mg·L-1) were significantly increased in the duodenum(P-1,adding berbamine hydrochloride to a concentration of 70 mg·L-1) were significantly increased in the ileum(PConclusion: Berbamine hydrochloride can promote the absorption of berberine hydrochloride in intestine to a certain extent,especially in the high calcium environment.

Application of augmented-reality surgical navigation technology combined with ICG molecular fluorescence imaging in laparoscopic hepatectomy / 中华外科杂志

Objective@#To study the application value of augmented-reality (AR) surgical navigation technology combined with indocyanine green (ICG) molecular fluorescence imaging in three-dimensional (3D) laparoscopic hepatectomy.@*Methods@#The clinical data of forty-eight patients who had undergone 3D laparoscopic hepatectomy for hepatocellular carcinoma at First Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University from January 2018 to April 2019 were retrospectively analyzed.The patients were divided into two groups: the group of 3D laparoscopic hepatectomy navigated by augment reality technology combined with ICG molecular fluorescence imaging (Group A) , and group of conventional 3D laparoscopic hepatectomy (Group B) . Patients in Group A (n=23) underwent 3D laparoscopic hepatectomy using augmented-reality technology combined with ICG molecular fluorescence imaging. In this group, the self-developed three-dimensional laparoscopic augmented-reality surgical navigation system (No. 2018SR840555) was operated to project the preoperative three-dimensional model to the surgical field, and the use of this system in combination with ICG molecular fluorescence imaging navigated laparoscopic hepatectomy. No surgical navigation technology was applied in Group B (n=25) . All patients signed the informed consent, which were in accordance with the requirements of medical ethics (Ethics No.: 2018-GDYK-003) . The preoperative data, surgical indicators and postoperative complications between the two groups were compared and analyzed.@*Results@#The median amount of intraoperative blood loss of Group A was 250 (200) ml (M (QR) ) , which was significantly lower than that of Group B (300 (150) ml) (Z=-2.307, P=0.021) .The transfusion rate of Group A was 13.0% (3/23) , which was significantly lower than that of Group B (40.0%, 10/25) (χ2=4.408, P=0.036) .The median postoperative hospitalization time of Group A was 8 (2) d, which was significantly shorter than that of Group B (11 (6.5) d) (Z=-2.694, P=0.007) . There were no serious complications and perioperative death in both groups.The incidence of postoperative complications in Group A was 17.4% (4/23) , which was not significantly different from that in group B (28%, 7/25) (χ2=0.763, P=0.382) .@*Conclusion@#Augmented-reality surgical navigation technology combined with ICG molecular fluorescence imaging has better effect in 3D laparoscopic hepatectomy.

Three-dimensional visualization combined with indocyanine green fluorescence imaging in diagnosis and treatment of primary hepatocellular carcinoma / 南方医科大学学报

OBJECTIVE@#To explore the value of three-dimensional visualization technology (3DVT) combined with indocyanine green (ICG) fluorescence imaging in the diagnosis and treatment of primary hepatocellular carcinoma (HCC).@*METHODS@#We retrospectively analyzed the clinical data of 154 patients with HCC admitted to the Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University between January, 2016 and November, 2018. In 57 of the patients (3DVT group), preoperative CT and Gd-EOB-DTPA-enhanced MRI were performed and 3D visualization and surgical planning was carried out before the operation; intraoperative ICG florescence imaging was performed for real-time detection of the tumor location and demarcation, intrahepatic satellite lesions and metastases. According to the intraoperative fluorescent signals and 3D visualization-based surgical planning, the final surgical plan was determined. In the other 97 patients (control group), conventional surgical assessment and surgical resection of the tumor was carried out. The preoperative imaging findings, intraoperative tumor detection, postoperative laboratory results, pathological reports, and follow-up data of the patients were analyzed.@*RESULTS@#In 3DVT group, 63 and 70 lesions were detected by preoperative CT and MRI, respectively; compared with CT examination, intraoperative ICG florescence imaging revealed additional 17 lesions, among which 10 were pathologically confirmed as HCC and 7 as cirrhosis nodules. The median volume of bleeding was 300 mL in 3DVT group, significantly less than that in the control group (400 mL; Z=2.291, =0.022). In both groups, serious complications or perioperative death occurred in none of the patients. The incidence of postoperative complications was significantly lowed in 3DVT group than in the control group [21% (12/57) 48.4% (47/97); =11.406, =0.001]. The overall disease-free survival rate at 2 years after the operation was significantly higher in 3DVT group than in the control group (74.9% 28.9%, =0.022).@*CONCLUSIONS@#3DVT combined with ICG fluorescence imaging allows precise preoperative diagnosis, surgical planning and implementation, intraoperative detection of small liver cancers and precise navigation for HCC treatment, thereby helping to reduce postoperative complications and improve the disease-free survival rate of the patients.

Explore the effect of Prunella vulgaris on TSH,TGAb,TPOAb and Th cell-related cytokine expression in AIT rats / 国际检验医学杂志

Objective To study and explore the effect of Prunella vulgaris on TSH 、TGAb 、TPOAb and Th cell-associated cytokines IFN-γ ,TNF-α ,IL-4 and IL-17 in autoimmune thyroiditis (AIT ) rats .Methods Di-vide forty female Sprague-Dawley rats into four group :blank group ,model group ,western medicine control group (selenium yeast group) ,Prunella vulgaris group ,10 rats in each group ,The rats in the model group and the rats in the model group were treated with PTg injection and high iodine water .The rats in the drug group were treated with sour yeast and Prunella vulgaris .The rats were sacrificed 6 weeks after the intervention . Elisa method was used to detect the rats Serum levels of TSH ,TGAb ,TPOAb and IFN-γ ,TNF-α ,IL-4 and IL-17 were measured .Results The levels of TSH ,TGAb ,TPOAb ,IFN-γ ,TNF-α ,IL-4 and IL-17 in the model group were significantly higher than those in the blank group ,the difference was statistically significant (P＜0 .05) .Selenium yeast group and Prunella vulgaris group TSH ,TGAb ,TPOAb ,IFN-γ ,TNF-α ,IL-4 ,IL-17 were lower than the model group ,the difference was statistically significant (P＜0 .05) ;The levels of TSH , IFN-γ ,IL-4 and IL-17 in Prunella vulgaris group were lower than those in selenium yeast group ,the difference was statistically significant (P＜0 .05) .Conclusion Prunella vulgaris can reduce the expression of autoanti-bodies and Th-related cytokines in AIT rats ,and have immunomodulatory effects ,it is worth to promote the use of clinical .

Is the Chinese medicinal formula Guipi Decoction () effective as an adjunctive treatment for depression? A meta-analysis of randomized controlled trials / 中国结合医学杂志

<p><b>OBJECTIVES</b>To evaluate the effectiveness and safety of Guipi Decoction (, GPD) as an adjunctive in the treatment of depression.</p><p><b>METHODS</b>A review of all relevant studies retrieved from a search of the following databases were conducted without any language restriction: Excerpt Medica Database (EMBASE), PubMed, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI), VIP Information, Wanfang Data, and the Chinese Biomedical Literature Database. Papers published until February 2013 were taken into consideration. The analysis was performed using the Cochrane software Revman 5.1.</p><p><b>RESULTS</b>Nine randomized controlled trials involving 620 patients with depression were included in this review. The meta-analysis revealed that compared with antidepressant therapy alone, treatment with a combination of GPD and an antidepressant drug signifificantly improved the symptoms of depression [weighted mean difference (WMD):-3.09; 95% confifidence interval (CI):-4.11 to-2.07] and increased the rates of effectiveness (OR: 4.75; 95% CI: 2.66-8.51) as well as recovery (OR: 1.73; 95% CI: 1.17-2.56). The adverse effects of GPD were not found to be signifificant in these studies.</p><p><b>CONCLUSIONS</b>The fifindings of this meta-analysis were in keeping with the notion that GPD formulations were effective in the treatment of depression without causing any serious adverse effects. However, currently available evidence was of low quality and therefore inadequate to justify a strong recommendation of using GPD formulations in the management of depression.</p>

Effects of intravitreous injection of different drugs combined with laser photocoagulation for macular edema secondary to retinal vein occlusion / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the effects and safety of intravitreal injection of triamcinolone acetonide ( TA ) or conbercept combined with macular laser grid photocoagulation in the treatment of macular edema secondary to retinal vein occlusion( RVO) . ·METHODS: Fifty cases ( 50 eyes ) with macular edema secondary to retinal vein occlusion were selected and assigned to 2 groups: intravitreal injection of TA or conbercept, and laser photocoagulation after 7d. Best corrected visual acuity ( BCVA ) , fundus examination, optical coherence tomography ( OCT ) and intraocular pressure ( IOP ) were examined before intravitreous injection and 14d, 1 and 3mo after laser, fundus fluorescein angiography(FFA) were examined 3mo after treatment. The postoperative results at each time point were compared with preoperative values. · RESULTS: Two kinds of treatment compared with preoperative, the BCVA all increased in various degrees. At 14d after intravitreous injection, 1 and 3mo after laser, the ratio of vision improved in TA group was 76%, 80%, 68%, conbercept group was 88%, 92%, 88%, BCVA of two groups in each period all had varying degrees of increase than preoperative. The best BCVA acquired at 1mo after treatment. The macular thickness after treatment was significantly lower than preoperative in two groups. At preoperative, 14d, 1 and 3mo after treatment, the macular thickness in TA group was 557. 5 ± 150. 9,301. 7±120. 1, 262. 7 ± 131. 2, 338. 1 ± 146. 5μm; the macular thickness in conbercept group was 569. 4 ± 135. 9, 282. 3 ± 133. 5, 259. 5 ± 116. 4, 307. 8 ± 122. 6μm. The macular thickness of the two groups were significantly different between preoperative and postoperative. · CONCLUSION: The combination of intravitreous injection of TA or conbercept with macular laser grid photocoagulation can be an effective method in the treatment of macular edema secondary to RVO, conbercept treatment is more effective and security.