A method for simultaneous determination of 21 kinds of Aconitum alkaloids(ATS)in biological specimens and infused liquor using ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)was developed.The biological samples were pretreated with methanol-acetonitrile(1∶2,V/V)for protein precipitation,while infused liquors were diluted 100-fold with acetonitrile,followed by centrifugation,and filtration by a 0.22-μm membrane.Chromatographic separation was carried out on an EC-C18 column using gradient elution with the mixture of 10 mmol/L ammonium acetate and 0.2%formic acid as mobile phase A and acetonitrile as mobile phase B.With this method,all the analytes were separated within 9.5 min.The samples were detected in positive ESI mode with dynamic multiple reaction monitoring(MRM)and quantified via external standard calibration.The results showed that the concentrations of the analytes in the range of 2-1000 ng/mL had excellent linearity(R2>0.9992)with the peak area.The developed method was successfully used for detection of 21 kinds of aconitum alkaloids,with limits of detection of 0.5-2 ng/mL,quantification limits of 2-6 ng/mL,intra/inter-day precision≤6.0%,spiked recoveries of 89.4%-100.9%,extraction recoveries of 74.2%-104.4%,and matrix effects ranging from-11.1%to 9.2%in blood/urine.The method was applied to detection of 12 samples from 4 fatal aconite poisoning cases,and all 21 kinds of ATS with total alkaloid concentrations of 0.04-4.18 μg/mL in blood and 154.96-422.83 μg/mL in medicinal liquors were detected.Tissue distribution revealed that the order of concentrations from highest to lowest is as follows:urine(157.22 μg/mL)>gastric contents(51.37 μg/mL)>kidney(21.6 μg/g)>whole blood(4.18 μg/mL)>liver(0.03 μg/g).This method showed many advantages such as simple pretreatment,low detection limits,accurate quantification,broad analyte coverage,and superior anti-interference capability in complex matrices,proving ideal for forensic and toxicological analysis of aconitum alkaloids.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

Because the classification system of radical surgery for rectal cancer has not been established, it is impossible to select the appropriate surgical method according to the clinical stage of the tumor. In this paper, we explained the theory of " four fasciae and three spaces " of pelvic membrane anatomy and then combined this theory with the membrane anatomical basis of Querleu-Morrow classification for radical cervical cancer resection. Based on this theory and the membrane anatomy of Querleu-Morrow classification of radical cervical cancer resection, we proposed a new classification system of radical rectal cancer surgery based on membrane anatomy according to the lateral lymph node dissection range of the rectum. This system classifies the surgery into four types (ABCD) and defines corresponding subtypes based on whether the autonomic nerve was preserved. Among them, type A surgery is total mesorectal excision (TME) with urogenital fascia preservation, type B surgery is classical TME, type C surgery is extended TME, and type D surgery is lateral extended resection. This classification system unifies the anatomical terminology of the pelvic membrane, validates the feasibility of using the " four fasciae and three fascial spaces " theory to classify rectal cancer surgery, and lays the theoretical foundation for the future development of a unified and standardized classification of radical pelvic tumor surgery.
Female ; Humans ; Uterine Cervical Neoplasms ; Rectal Neoplasms/pathology* ; Rectum/anatomy & histology* ; Pelvis/innervation* ; Proctectomy

As a treatment of rectal cancer, lateral lymph node dissection (LLND) is still a controversial issue. The argument against LLND is that the procedure is complicated, and consequently results in a high incidence of postoperative urogenital dysfunction. The surgical modality from fascia to space is adopted by lateral lymph node dissection in "two spaces". This operation has significant advantages of clear location of nerves and blood vessels and simplified surgical procedures, so the surgical procedure can be repeated and modulated. The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia constitute the dissection plane for lateral lymph node dissection.Two spaces refer to Latzko's pararectal space and paravesical space. During the establishment of fascia plane, the dissection of external iliac lymph node (No.293), commoniliac lymph node (No.273) and abdominal aortic bifurcation lymph node (No.280) can be performed. While in the "space" dissection, internal iliac lymph node (No.263), obturator lymph node (No.283), lateral sacral lymph node (No.260) and median sacral lymph node (No.270) can be removed. LD2 or LD3 lateral lymph node dissection prescribed by the Japanese Society of Colorectal Cancer can be completed according to the needs of the disease. This article describes the anatomical basis and standardized surgical procedures.
Dissection ; Fascia/pathology* ; Humans ; Lymph Node Excision/methods* ; Lymph Nodes/pathology* ; Rectal Neoplasms/surgery*

Despite the concept of membrane anatomy has been widely used in minimally invasive colorectal surgery, the definition of membrane anatomy and the establishment of membrane plane remain controversial. Therefore, it is difficult to establish a unified theoretical system of membrane anatomy. Through embryological studies and anatomical findings on the integrity and continuity of membranes, we try to discuss the theoretical system of membrane anatomy in colorectal surgery from three aspects: membrane anatomical system, membrane anatomical elements and membrane anatomical mechanism. The establishment of a unified theoretical system of membrane anatomy will not only contribute to the standardization operative procedures, but also to the establishment of uniform surgical standards for colorectal cancer.
Colorectal Surgery ; Digestive System Surgical Procedures ; Fascia ; Humans ; Mesentery ; Minimally Invasive Surgical Procedures

Objective A/H1N1(pdm09) viruses were the dominant strains in Shanghai during 2018-2019 influenza surveillance year.This study is to provide a scientific reference for clinical drug use by investigating the susceptibility of A/H1N1(pdm09) viruses to neuraminidase inhibitors(NAIs). Methods Sixty strains of A/H1N1(pdm09) viruses were randomly selected for testing the susceptibility and drug resistance to Oseltamivir and Zanamivir by means of neutaminidase inhibition and neuraminidase (NA) gene sequencing. Results The 60 epidemic strains all proved to be susceptible to Oseltamivir and Zanamivir and the susceptibility was not observed to be decreased or remarkably decreased.In genetic sequencing, NA was not observed to present amino acid mutation at the key sites and auxiliary sites in catalytic activity, which confirmed the results of the phototypic detection of neuraminidase inhibition. Conclusion The subtype influenza viruses A/H1N1(pdm09) circulating in Shanghai during 2018-2019 surveillance year are still sensitive to NAIs, which provides a scientific reference for clinical use of drugs.However, we monitored only a number of strains and think that the work monitoring antiviral susceptibility should be continued with the wide use of the drugs.

PURPOSE: To summarize and analyze the early treatment of multiple injuries combined with severe pelvic fractures, especially focus on the hemostasis methods for severe pelvic fractures, so as to improve the successful rate of rescue for the fatal hemorrhagic shock caused by pelvic fractures. METHODS: A retrospective analysis was conducted in 68 cases of multiple trauma combined with severe pelvic fractures in recent 10 years (from Jan. 2006 to Dec. 2015). There were 57 males and 11 females. Their age ranged from 19 to 75 years, averaging 42 years. Causes of injury included traffic accidents in 34 cases (2 cases of truck rolling), high falling injuries in 17 cases, crashing injuries in 15 cases, steel cable wound in 1 case, and seat belt traction injury in 1 case. There were 31 cases of head injury, 11 cases of chest injury, 56 cases of abdominal and pelvic injuries, and 37 cases of spinal and limb injuries. Therapeutic methods included early anti-shock measures, surgical hemostasis based on internal iliac artery devasculization for pelvic hemorrhage, and early treatment for combined organ damage and complications included embolization and repair of the liver, spleen and kidney, splenectomy, nephrectomy, intestinal resection, colostomy, bladder ostomy, and urethral repair, etc. Patients in this series received blood transfusion volume of 1200-10,000 mL, with an average volume of 2850 mL. Postoperative follow-up ranged from 6 months to 1.5 years. RESULTS: The average score of ISS in this series was 38.6 points. 49 cases were successfully treated and the total survival rate was 72.1%. Totally 19 patients died (average ISS score 42.4), including 6 cases of hemorrhagic shock, 8 cases of brain injury, 1 case of cardiac injury, 2 cases of pulmonary infection, 1 case of pulmonary embolism, and 1 case of multiple organ failure. Postoperative complications included 1 case of urethral stricture (after secondary repair), 1 case of sexual dysfunction (combined with urethral rupture), 1 case of lower limb amputation (femoral artery thrombosis), and 18 cases of consumptive coagulopathy. CONCLUSION The early treatment of multiple injuries combined with severe pelvic fractures should focus on pelvic hemostasis. Massive bleeding-induced hemorrhagic shock is one of the main causes of poor prognosis. The technique of internal iliac artery devasculization including ligation and embolization can be used as an effective measure to stop or reduce bleeding. Consumptive coagulopathy is difficult to deal with, which should be detected and treated as soon as possible after surgical measures have been performed. The effect of using recombinant factor VII in treating consumptive coagulopathy is satisfactory.
Adult ; Embolization, Therapeutic ; methods ; Factor VII ; administration & dosage ; Female ; Fractures, Bone ; complications ; therapy ; Hemostasis, Surgical ; Humans ; Iliac Artery ; surgery ; Injury Severity Score ; Ligation ; Male ; Middle Aged ; Multiple Trauma ; complications ; therapy ; Pelvic Bones ; injuries ; Prognosis ; Recombinant Proteins ; administration & dosage ; Retrospective Studies ; Shock, Hemorrhagic ; etiology ; prevention & control ; Young Adult

Objective To investigate the clinical distribution and antimicrobial resistance of carbapenem-resistant Enterobacteriaceae (CRE) in Dongguan.Methods CRE isolated from hospitalized patients in 22 secondary and above medical institutions which participated in bacterial monitoring in Dongguan between January 2015 and June 2016 were retrospectively analyzed,antimicrobial resistance was analyzed by WHONET 5.6 software.Results A total of 71 CRE isolates were detected,with a isolation rate of 0.34％ (71/20 713).53 strains(74.65％) of CRE were isolated from patients aged 15-60 years old;46 (64.79 ％) were from male patients;CRE were mainly isolated from patients in intensive care unit(36 strains,50.70 ％);the main specimen was sputum(34 strains,47.89 ％),followed by urine (11 strians,15.49 ％) and wound secretion(6 strains,8.45 ％);the main infection type was healthcare associated infection (64 strains,90.14 ％);CRE were mainly distributed in tertiary hospitals(56 strains,78.87 ％),the isolation rate of CRE in tertiary and secondary hospitals were 0.41 ％(56/13 677)and 0.21％(15/7 036) respectively.71 strains of CRE were all resistant to imipenem,resistance rate to meropenem was 81.12％,only amikacin and tobramycin had drug resistance rates of ＜40％ (21.38％ and 38.79％ respectively),resistance rate to trime thoprim/sulfamethoxazole was 48.23 ％,while resistance rates to fluoroquinolones,third-generation cephalosporins,and enzyme inhibitors were all＞60.Conclusion The isolation rate of CRE in Dongguan is lower than that of the whole nation and the other provinces,effective prevention and control measures should be taken according to the key population and departments that isolated CRE,antimicrobial use should be rational.

Objective: To investigate the anti-proliferation effect and mechanism of zoledronic acid (ZOL) on human colon cancer line SW480. Methods: SW480 cells were treated with 0, 12.5, 25, 50, 100 and 200 μmoL/L of ZOL for 48 h, and CCK-8 assay was employed to obtain the survival rate of SW480 cells. SW480 cells were treated with 25 μmoL/L of ZOL for 0, 12, 24, 48 and 72 h, and then the survival rate was obtained. SW480 cells of the ZOL group were treated with 25 μmoL/L of ZOL for 48 h, while cells of the CsA + ZOL group were pretreated with 10 μmoL/L of CsA for 0.5 h and then treated with 25 μmoL/L of ZOL for 48 h. Then the survival rates of SW480 cells of the control group, ZOL group and CsA + ZOL group were determined. Flow cytometry was employed to detect the apoptosis rate and the mitochondrial transmembrane potential (▵Ψm) of the three groups and Western blot was used to detect the expressions of cyt C in the cytosol of the three groups. Results: ZOL inhibited the proliferation of SW480 cells, and the inhibition rate positively correlated with the concentration of ZOL and the action time (P < 0.01). The cell survival rate and the ▵Ψm of the ZOL group were greatly lower than those of the control group, while the apoptosis rate and the expression of cyt C in the cytosol were obviously higher than those of the control group. All the differences showed distinctly statistical significances (P < 0.01). The cell survival rate and the ▵Ψm of the CsA + ZOL group were all lower than those of the control group, but substantially higher than those of the ZOL group; while the apoptosis rate and the expression of cyt C in the cytosol were higher than those of the control group, but distinctly lower than those of the ZOL group. All the differences were statistically significant (P < 0.01). Conclusions: ZOL can induce the apoptosis in human colon cancer line SW480 and then inhibit the proliferation of SW480 cells directly by opening the mitochondrial permeability transition pore abnormally, decreasing ▵Ψm, and releasing the cyt C into the cytosol. And the effect enhances with the increases of the concentration of ZOL and the action time.

Total mesorectal excision (TME) is being established as the gold standard for rectal cancer surgery, however sexual and urinary dysfunction is an established risk after TME. By cadaver dissections, we clarify the correct surgical plane for TME and further determine the relation between the surgical plane and pelvic autonomic nerves. It must be noted that the pelvic plexus can be divided into 2 categories: aggregated shape and diffused shape. The latter is in tight contact with visceral fascia, which seems to be inseparable from each other by sharp dissection. Therefore, it is necessary to study the function of different units in pelvic plexus.
Humans ; Hypogastric Plexus ; anatomy & histology ; injuries ; Rectal Neoplasms ; surgery