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In recent years, monotherapy and combination therapy with immune checkpoint inhibitors (ICIs) have achieved good efficacy in a variety of malignancies from solid tumors to lymphomas and have become a standardized and systematic treatment modality for many cancers. However, there is still a lack of studies on the safety of ICIs in hepatitis B virus (HBV)-infected patients with malignancies, and early studies have reported HBV reactivation due to ICI antitumor therapy in clinical practice. With reference to related literature, this article reviews the recent clinical trials and application of ICIs in cancer patients with chronic viral infection and clarifies the efficacy and safety of ICIs in this special population, in order to provide a reference for clinical medication.
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Liver transplantation, as one of the radical treatment strategies for hepatocellular carcinoma, has a good clinical effect in patients meeting the Milan criteria; however, the high recurrence rate and metastasis rate after surgery bring great challenges to the long-term survival of such patients. Therefore, how to improve long-term survival rate and reduce postoperative tumor metastasis has become a key problem that needs to be solved urgently. In recent years, immune checkpoint inhibitors (ICIs), with their good safety and objective reactivity, have provided a new opportunity for the treatment of patients with advanced liver cancer and have become potential candidates for improving the therapeutic effect of liver transplantation. At present, early clinical studies have reported the unique advantages of ICIs used alone or in combination in downstaging or bridging therapy before liver transplantation for hepatocellular carcinoma and adjuvant therapy after liver transplantation. Therefore, this article reviews the clinical trials of ICIs in liver transplantation for hepatocellular carcinoma and the advances in the application of ICIs in recent years and discuss its safety and efficacy, in order to provide a certain reference for clinical medication.
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Objective:To study the safety and efficacy of laparoscopic cholecystectomy (LC) in treatment of T2a and lower stages of gallbladder carcinoma.Methods:A retrospective study was performed on patients who were diagnosed with gallbladder cancer and underwent surgical treatment from January 2016 to January 2021 at Hunan Provincial People's Hospital. These patients were divided into the simple treatment group and the radical treatment group based on the surgical methods used. The simple treatment group consisted of 64 patients who underwent LC for accidental gallbladder cancers. The radical treatment group consisted of 30 patients who underwent laparoscopic radical cholecystectomy (LRC). The baseline characteristic of the two groups of patients were matched in a 1∶1 ratio using propensity score matching. After matching, there were 26 patients in each of the 2 groups. There were 7 males and 19 females in the simple group, with mean ± s. d. age of (60.6±9.6) years. There were 8 males and 18 females, with mean ± s. d. age (60.9±9.1) years in the radical treatment group. Blood loss, operation time, postoperative hospital stay, biliary leakage, acute pulmonary embolism, and incisional infection were compared between the two groups.Results:In the simple group, the operative time was (78.7±62.9) min, intraoperative blood loss was (10.7±11.6) ml and postoperative hospital stay was (4.4±2.6) d. These results were significantly better than those in the radical group with operative time (298.7±101.3) min, intraoperative blood loss (161.9±96.7) ml and postoperative hospital stay (9.9±4.0) d (all P<0.05). There were no significant difference in the postoperative complications and disease free survival rates between the two groups (both P>0.05). Conclusion:LC was safe and effective for treatment of T2a and lower stages of gallbladder cancer, and it could achieve a similar disease-free survival rate as LRC.
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Objective To evaluate the safety and efficacy of irreversible electroporation (IRE) combined with neoadjuvant chemotherapy in patients with locally advanced pancreatic cancer. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, CNKI, Wanfang, and VIP databases for articles dated from the establishment of each database to March 2022. Meta-analysis was performed using RevMan5.4 software. Results A total of 3970 patients with locally advanced pancreatic cancer were enrolled in eight studies, including one randomized controlled trial, four retrospective studies, and three prospective studies. The patients were divided into the combined therapy group with 344 patients and the chemotherapy-only group with 3626 patients. Meta-analysis showed that the overall survival of patients in the combined therapy group was significantly higher than that in the chemotherapy-only group (OR=4.52; 95%CI: 2.63-7.77; P < 0.00001). However, no significant difference existed in the disease control rate between the combined therapy group and the chemotherapy-only group (OR=0.58; 95%CI: 0.02-18.74; P=0.76). Moreover, no significant difference existed in the disease progression between the two groups (OR=0.49; 95%CI: 0.23-1.02; P=0.06). The combination of neoadjuvant chemotherapy and IRE had no significant effect on the incidence of adverse reactions of gastrointestinal reaction (OR=0.37; 95%CI: 0.10-1.34; P=0.13) and bone marrow suppression (OR=0.61; 95%CI: 0.26-1.40; P=0.24). Conclusion IRE combined with neoadjuvant chemotherapy can remarkably improve the prognosis of patients with locally advanced pancreatic cancer, and significantly prolong the overall survival.
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Nonalcoholic fatty liver disease is a common chronic liver disease with the risk of progression to nonalcoholic hepatitis, liver fibrosis, and hepatocellular carcinoma. Nonalcoholic fatty liver disease has various pathogeneses, among which abnormal metabolism of branched-chain amino acids can induce oxidative stress, autophagy, and mitochondrial dysfunction in hepatocytes and is the most important mechanism in the development and progression of nonalcoholic fatty liver disease. This article reviews related research advances and analyzes the possible role of abnormal metabolism of branched-chain amino acids in the development and progression of nonalcoholic fatty liver disease, in order to improve clinical awareness and diagnosis.
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Objective:To compare between laparoscopic and open pancreaticoduodenectomy in the treatment of distal cholangiocarcinoma.Methods:The clinical data of laparoscopic pancreaticoduodenectomy (LPD group, n=101) and open pancreaticoduodenectomy (OPD group, n=99) in patients with distal cholangiocarcinoma who underwent pancreaticoduodenectomy at Hunan people's Hospital from Jan 2015 to Dec 2019 were analyzed retrospectively. The operation time, intraoperative blood loss, number of lymph node dissection, R 0 resection rate, postoperative hospital stay, postoperative complications and overall survival rate were compared between the two groups. Results:The operation time was (475.0±90.7) min and (444.8±63.3) min, the intraoperative blood loss was (350.9±397.9) ml and (546.7±642.9) ml, the postoperative hospital stay was (11.5±4.7) d and (13.3±5.1) d, the differences were statistically significant ( P<0.05).The number of lymph node dissection was 14.8±3.0 and 15.4±2.4, the R 0 resection rate was 93.1% and 96.0%, respectively, and there was no significant difference ( P>0.05). There was no significant difference in the incidence of residual complications ( P>0.05). During the follow-up of 5-64 months, the OS of 1, 3 and 5 years in the two groups were 90.4%, 41.3%, 20.6% and 94.3%, 50.8% and 24.7%, respectively. ( P>0.05). Conclusions:LPD is safe and feasible in the treatment of distal cholangiocarcinoma, and its short-term curative effect, curative effect and long-term overall survival rate are similar to those of OPD.
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Objective:To compare the safety and efficacy of laparoscopic versus open pancreaticoduodenectomy.Methods:The clinical data of 989 patients who underwent pancreaticoduodenectomy at Hunan People's Hospital from January 2015 to December 2019 were analyzed retrospectively. There were 349 patients in the laparoscopic pancreaticoduodenectomy (LPD) group and 640 patients in the open pancreaticoduodenectomy (OPD) group. Propensity score matching (PSM) was used to match the baseline data of the two groups at a 1: 1 ratio. Data including operation time, intraoperative bleeding, postoperative hospital stay, bile leakage, pancreatic fistula and wound infection were compared between the two groups.Results:After PSM, there were 345 patients in each of the 2 groups. When the LPD group was compared with the OPD group, there were no significant differences in postoperative mortality, reoperation, intraoperative blood transfusion, pancreatic fistula, bile leakage, abdominal hemorrhage, abdominal abscess, severe complications, and pulmonary complication rates. The number of lymph node dissected, R 0 resection and overall survival rates between the two groups were also not significantly different ( P>0.05). However, the operation time of the LPD group (478.2±91.3) min was significantly longer than that of the OPD group (410.8±62.0) min ( P<0.05). On the other hand, the postoperative hospitalization time (10.8±4.3) d, intraoperative bleeding (322.0±362.6) ml, wound infection rate 1.2% (4/345) in the LPD group were significantly better than those in the OPD group [postoperative hospitalization time (12.5±7.9) d, intraoperative bleeding (478.8±570.2) ml, and wound infection rate 5.8% (20/345)] ( P<0.05) . Conclusion:LPD was safe and feasible, and it achieved similar curative effect as OPD.
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Objective To establish an UHPLC-MS/MS method for the determination of uracil (U) and dihydrouracil (UH2) in human plasma. Methods A positive ion detection mode was adopted on the Agilent 6460A mass spectrometer. Chlorouracil was used as the internal standard. 3% bovine serum albumin was used as surrogate plasma matrix. The pretreatment of plasma sample was completed based on liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved on an Agilent Poroshell 120 SB-Aq (2.1 mm×100 mm, 2.7 μm) column with gradient elution. The mobile phase was 5 mmol/L ammonium acetate aqueous solution and acetonitrile solution. The flow rate was 0.3 ml/min. The column temperature was 30°C. The injection volume was 5 μl. Results The linear range of uracil and dihydrouracil was 10.0-1500.0 ng/ml. Both of uracil and dihydrouracil had good linear relationship with correlation coefficient (r)>0.990. Both of inter- and intra-day precision was <15%. Conclusion The established method is simple, selective, and suitable for the determination of U and UH2 in human plasma.
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Objective To investigate the extraction methods for active components from oral ulcer film and optimize the determination methods of active components dexamethasone sodium phosphate and metronazole. Methods Different extraction solvents(methanol, water and 70% methanol aqueous) were applied to extract the active components dexamethasone sodium phosphate and metronazole from oral ulcer film, which contents were quantified by a HPLC method. Results the extraction solvent water had the best efficacy and more simpler compared to the other two solvents. Clotriazole showed a good linear relationship within 5.014 5-200.5800 μg/ml (r=0.999 8), and the average extraction recovery was (104.23±0.63)%, and for dexamethasone sodium phosphate, a good linear relationship was obtained in the range of 0.482-16.328 μg/ml (r=0.9999), and the average extraction recovery was (103.97±1.02)%. Conclusion The water extraction method established in this study was simple and efficient, which showed features of simplicity, accuracy and repeatable.
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Objective To analyze the correlation of valproic acid and its metabolites (2-propyl-4-pentenoic acid, 3-hydroxy valproic acid,5-hydroxy valproic acid) with liver injury reference index. Methods 328 plasma samples from epilepsy patients were collected and divided into two groups（123 samples from patients with abnormal liver function, experimental group; 205 samples from patients with normal liver function, control group）.The plasma concentrations of valproic acid and its metabolites in the two groups were determined by LC-MS/MS method and the diagnostic value of the concentrations to liver disfunction was analyzed by ROC curve. Results The mean plasma concentration of valproic acid and its three metabolites in the patients with abnormal liver function was higher than that in the control group with was statistically difference（P<0.05）.The concentration of valproic acid and its metabolites could be used as a reference for the diagnosis of liver injury,5-hydroxy valproic acid had better diagnostic value than valproic acid. Conclusion The metabolites of valproic acid were associated with hepatotoxicity, which could be used as a diagnostic index of liver injury and could be a reference for clinical safe application of valproic acid.
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Objective@#To explore the clinical effects of artificial dermis combined with vacuum sealing drainage (VSD) and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn.@*Methods@#A total of 8 patients with scar hyperplasia and contracture deformity on joint after healing of extensive burn were admitted to our hospital from August 2015 to August 2017. There were 5 females and 3 males aged 8 to 45 years with an average of 23 years. In the first stage operation, scar tissue on contracture site was removed, and the wound was covered by artificial dermis followed by continued VSD treatment. On 10-14 d after the first stage operation, the artificial dermis tissue formed, and the second stage autologous split-thickness skin grafting and continued VSD treatment were performed. Routine anti-scar therapy was carried out after healing of wounds. Time of wound healing after the second stage operation was recorded. Colour and texture of the split-thickness skin graft, scar formation condition of the donor site, and action condition of the operation site during follow-up were observed.@*Results@#The wounds of 8 patients were healed in 10-14 d after the second stage operation. During follow-up of 6-24 months, the split-thickness skin graft was with smooth surface and good elasticity, and the function of joint recovered well. The donor site in head healed well with no scar. Only pigmentation was left in the donor site of thigh, and scar was not obvious. The patients and their family members were satisfied.@*Conclusions@#After application of artificial dermis combined with VSD and autologous split-thickness skin graft in repair of scar contracture deformity after extensive burn, the skin grafting area and donor site were with unobvious scar hyperplasia, and the joint function in the operation area was good.
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Objective To investigate the value of high frequency ultrasound combined with color Doppler flow imaging in diagnosis and classification of trauma of penis on the clinical treatment . Methods T he sonographic features of 48 cases with penile trauma were analyzed and compared with treatment outcomes . Results T he ultrasonic findings of penile trauma ranged from penis contusion to penis fracture . According to the sonographic features ,the trauma of penis was grouped as follow s :Type 1 ,penis bruise ( 7 cases) presented with images of continuous penis skin and tunica albuginea ,inhomogeneous echoes of subcutaneous tissue . Type 2 ,corpora cavernosa bruise ( 4 cases ) showed images of continuous tunica albuginea ,inhomogeneous internal echoes of corpora cavernosa without abnormal flow signal . T he corpora cavernosa swelling into honeycomb‐like ,anechoic area of cavernosa with high‐speed artery Doppler signals w hen accompanied by cavernous artery injury . Four cases were treated conservatively . Type 3 ,the skin and subcutaneous tissue contusion ( 6 cases) manifested images of incontinuous and inhomogeneous echoes of skin and subcutaneous tissue but homogeneous echoes of corpora cavernosa and tunica albuginea . Six cases of patients underwent debridement and sutured by local anesthesia . Type 4 ,rupture of tunica albuginea( 26 cases) revealed images of incontinuous and irregular local tunica albuginea ,a hematoma seen between the tunica albuginea and subcutaneous tissue . Type 5 , penile fracture ( 5 cases ) revealed mostly or fully disconnected skin and corpora cavernosa ,tearing of blood vessels . T he patients of type 4 and 5 were all treated surgically . Conclusions Color Doppler ultrasonography could provide accurate assessment and classification for trauma of penis ,w hich is helpful to offer a reliable basis for clinical treatment scheme .
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Objective To analyze the ultrasonic features of papillary thyroid microcarcinoma (PTMC) with different size and location,and to investigate the relationship of aspect transverse ratio (A/T) and capsule invasion in PTMC.Methods Totally 407 patients of PTMC with 495 nodules confirmed by pathology were enrolled.The nodules were divided into largest diameter≤0.5 cm group and largest diameter＞0.5 cm group.The ultrasonic signs of nodules were observed,and the relationship between A/T and thyroid capsule invasion was analyzed.Results The differences of blood type,relationship with capsule,calcification,morphology and A/T were statistically significant between the two groups (all P＜0.05).In nodules closed to capsule and A/T≥1,the rate of capsule invasion in diameter＞0.5 cm group (117/185,63.24％) was higher than that in diameter≤0.5 cm group (25/61,40.98％,P＜0.01).Taking A/T≥1 as the standard,the sensitivity of A/T in estimating capsule invasion of nodules closed to capsule in diameter≤0.5 cm group and diameter＞ 0.5 cm group was 89.29％ and 73.58％,the specificity was 29.41％ and 37.61％,respectively.In nodules adjacent to capsule and broken through capsule,the difference of capsule invasion rate was not significant between nodules with A/T≥1 and A/T＜1 (both P＞0.05).In nodules that contact capsule,the capsule invasion rate of A/T≥1 nodules (46/67,68.66％) was higher than that of A/T＜1 (10/27,37.04％).Taking A/T≥1 as the standard,the sensitivity of A/T in estimating capsule invasion of nodules touched capsule was 82.14％,and the specificity was 44.74％.Conclusion Ultrasonography can show the size,A/T and relationship with capsule in PTMC,which can provide diagnostic evidences in judging capsule invasion of PTMC.
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OBJECTIVE@#To investigate the anti-proliferative effects of saponins prepared from Plena Clematis (PC) cultured in Fujian Province, China on 4 human tumor cell lines and its possible anti-tumor mechanism.@*METHODS@#The growth inhibition assays of saponins on human esophageal squamous carcinoma cell line (EC9706), human hepatoma cell line (HepG-2), human oral cancer cell line (KB) and human gastric cancer cell line (BGC-823) were evaluated in vitro by thiazolyl blue (MTT) method. The inhibitory effects on EC9706 treated with different concentrations of saponins (15.62, 31.25, 62.50, 125, 250 and 500 μg/mL) were performed in vitro by MTT method. The morphology and nuclear staining with acridine orange/ethidium bromide of EC9706 cells treated with saponins were illustrated under an inverted phase fluorescence microscope. The apoptotic effects of saponins were further evaluated by annexin-V/propidium iodide dual staining experiment to examine the occurrence of phosphatidylserine externalization onto the cell surface by a flflow cytometer.@*RESULTS@#MTT assay showed that the saponins could inhibit the proliferation of 4 tumor cell lines. Among them, the maximum inhibition rate of 73.1% was detected in EC9706 cells at the saponins concentration of 250 μg/mL for 24 h. Further investigation indicated that the saponins induced EC9706 cells apoposis. The EC9706 cells presented apoptotic characteristics when treated with saponins, including that the morphologies of EC9706 cells were appeared round-shaped with higher refraction, and the cell nuclear stained orange with EB after 250 μg/mL saponins exposure. The flow cytometry analysis results showed that the induction of cell cycle arrest in apoptotic system may participate in the anti-proliferative activity of saponins on EC9706 cells.@*CONCLUSION@#The saponins from PC exhibited significant cytotoxicity against human EC9706, KB, BGC-823, and HepG-2 cells and might be beneficial to development of ethnic pharmaceutical plant for potential anti-tumor drugs.
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Humans , Antineoplastic Agents, Phytogenic , Pharmacology , Cell Cycle Checkpoints , Cell Line, Tumor , Cell Proliferation , Clematis , Chemistry , Saponins , PharmacologyABSTRACT
Objective To establish the quality standard of Santeng oral solution.Method Sargentodoxa Caulis and Spatholobi Caulis were identified by thin layer chromatography.Chlorogenic acid was assayed by high performance liquid chromatography.The chromatographic column is Agilent Zorbax SB C18 (4.6 mm×250 mm, 5 μm) with a stable temperature of 35 ℃.The mobile phase in isocratic elution consists of acetonitrile and 0.1% folic acid aqueous solution with a preliminary volume ratio of 9∶91.The flow rate is 1.0 ml/min with an injection volume of 20 μl.Results Thin layer chromatography showed distinct spots of Sargentodoxa Caulis and Spatholobi Caulis with a great specificity.A regression formula Y=60.14X-6.37(r>0.999 9) was obtained with a good linearity in concentration range of 2.70~202.50 μg/ml.Conclusion A simple, stable and repeatable method was established for the quality control of Santeng oral solution.
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Noise-induced hearing loss (NIHL) is a complex disease caused by interactions between environmental and genetic factors. This study investigated whether genetic variability in protocadherin related 15 (PCDH15) underlies an increased susceptibility to the development of NIHL in a Chinese population. The results showed that compared with the TT genotype of rs11004085, CT/CC genotypes were associated with an increased risk of NIHL [adjusted odds ratio (OR) = 2.64; 95% confidence interval (CI): 1.14-6.11, P = 0.024]. Additionally, significant interactions between the rs11004085 and rs978842 genetic variations and noise exposure were observed in the high-level exposure groups (P < 0.05). Furthermore, the risk haplotype TAGCC was observed when combined with higher levels of noise exposure (P < 0.05). Thus, our study confirms that genetic variations in PCDH15 modify the susceptibility to NIHL development in humans.
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Humans , Cadherins , Genetics , China , Genetic Predisposition to Disease , Genetic Variation , Hearing Loss, Noise-Induced , Epidemiology , Genetics , Risk FactorsABSTRACT
Post-exposure prophylaxis (PEP) has proved to be the most important measure for rabies prevention and control. There is little information regarding adverse reactions to the Essen and 2-1-1 regimens in preschool children (aged 0-6). We reexamined the outcomes of 1,109 preschool children who were vaccinated using SPEEDA under the Essen regimen between January 2011 and December 2012 and 1,267 preschool children under the 2-1-1 regimen between January 2013 and December 2014. We find that, in preschool children, the febrile reaction after the first 2-dose injection in the 2-1-1 regimen was significantly higher than that induced by the first 1-dose in the Essen procedure. Thus, we recommend that the Essen regimen should still be used for rabies PEP in preschool children.
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Child , Child, Preschool , Humans , Infant , Germany , Post-Exposure Prophylaxis , Reference Standards , Rabies , Rabies Vaccines , VaccinationABSTRACT
OBJECTIVE:To establish a method for simultaneous determination of 4 psoralen compounds in Buwu tincture. METHODS:HPLC was performed on the column of Dikma Diamonsil C18 with mobile phase of acetonitrile-0.2% Acetic acid by gradient elution at flow rate of 1 ml/min,detection wavelength was 246 nm,column temperature was 30 ℃,and the injection vol-ume was 15 μl. RESULTS:The linear range was 13.00-208 μg/ml for angelicin,26.00-416 μg/ml for bavachin,24.50-392 μg/ml for psoralidin and 37.88-606 μg/ml for isobavachalcone,respectively(r≥0.999 6);RSDs of precision,stability and reproducibility tests were less than 2.00%;recoveries were 95.22%-97.23%(RSD=0.87%,n=6),100.24%-104.64%(RSD=1.62%,n=6), 102.28%-104.39%(RSD=1.47%,n=6)and 97.68%-100.17%(RSD=0.97%,n=6),respectively. CONCLUSIONS:The method is simple and reproducible,and can be used for the quality control of Buwu tincture.
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Objective To explore the way of contrast-enhanced ultrasound(CEUS)and quantitative analysis technology to assess testicular microvascular ischemia-reperfusion inj ury.Methods Twenty-four healthy adult rabbits were randomly divided into the control group and the microvascular mild,moderate, serve ischemic inj ury group (group Ⅰ,including group Ⅰ1 ,Ⅰ2 ,Ⅰ3 ).The spermatic cord of the control group were threaded but not ligated.The group Ⅰ1 ,Ⅰ2 ,Ⅰ3 were reperfused 2 h after 2 h,4 h,6 h complete testicular ischemia respectively.The ultrasound contrast angiographic parameters of each group were analyzed by the quantitative analysis techniques,including peak intensity(PI),time to peak(TP),slope,mean transmit time(MTT),DT/2 and area.The levels of plasma vWF,NO and ET-1 were tested after the CEUS. The pathological changes of the ipsilateral testicular were observed by the HE and immunohistochemical staining.Statistical analysis was performed by SPSS 13.0 software.Results Preoperativeiy,each parameter of the experimental group and the control group showed no statistical significance (P > 0.05 ). Postoperatively,the PI,slope,area of the group Ⅰ1 increased significantly,while the TP,MTT were prolonged(P <0.05).Contrast time-intensity curve was significantly higher peak and retrusion.The groupⅠ2's PI,slope,area increased further,DT/2 was significantly prolonged,but TP significantly reduced (P <0.05).The contrast curve significantly increased,forward and decreased slowly.The contrast curves of the group Ⅰ3 was approximate a straight line.The vWF,NO,ET-1 levels of each experimental group were significantly higher than those in control group (P <0.05),among them,the levels of group Ⅰ2 were the highest (P <0.05 ).With the aggravation of ischemia,the testicular capillaries expansion,erythrocyte sedimentation,leakage,infiltration of inflammatory cells,MMP-9 expression in vascular basement membrane gradually increased.Conclusions The CEUS and quantitative analysis techniques can effectively evaluate testicular microvascular inj ury.
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Until now, more than seventeen parvovirus have been reported which can infect mammals and poultries. The infected cells appeared different properties of apoptosis and death, present a typical cytopathic effect. NS1 is a major nonstructural protein of parvovirus, with a conservative structure and function, which plays an important role in the viral life cycle. In addition to the influence on viral replication, the NS1 also participates in apoptosis induced by viruses. Parvovirus induced apoptosis which is mainly mediated by mitochondrial pathway, this review summarized the latest research progresses of parvovirus induced apoptosis.