Mechanism of n-butanol alcohol extract of Baitouweng Decoction in treatment of vulvovaginal candidiasis based on negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis / 中国中药杂志

This study aimed to explore the mechanism of n-butanol alcohol extract of Baitouweng Decoction(BAEB) in the treatment of vulvovaginal candidiasis(VVC) in mice based on the negative regulation of NLRP3 inflammasome via PKCδ/NLRC4/IL-1Ra axis. In the experiment, female C57BL/6 mice were divided randomly into the following six groups: a blank control group, a VVC model group, high-, medium-, and low-dose BAEB groups(80, 40, and 20 mg·kg~(-1)), and a fluconazole group(20 mg·kg~(-1)). The VVC model was induced in mice except for those in the blank control group by the estrogen dependence method. After modeling, no treatment was carried out in the blank control group. The mice in the high-, medium-, and low-dose BAEB groups were treated with BAEB at 80, 40, and 20 mg·kg~(-1), respectively, and those in the fluconazole group were treated with fluconazole at 20 mg·kg~(-1). The mice in the VVC model group received the same volume of normal saline. The general state and body weight of mice in each group were observed every day, and the morphological changes of Candida albicans in the vaginal lavage of mice were examined by Gram staining. The fungal load in the vaginal lavage of mice was detected by microdilution assay. After the mice were killed, the degree of neutrophil infiltration in the vaginal lavage was detected by Papanicolaou staining. The content of inflammatory cytokines interleukin(IL)-1β, IL-18, and lactate dehydrogenase(LDH) in the vaginal lavage was tested by enzyme-linked immunosorbent assay(ELISA), and vaginal histopathology was analyzed by hematoxylin-eosin(HE) staining. The expression and distribution of NLRP3, PKCδ, pNLRC4, and IL-1Ra in vaginal tissues were measured by immunohistochemistry(IHC), and the expression and distribution of pNLRC4 and IL-1Ra in vaginal tissues were detected by immunofluorescence(IF). The protein expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by Western blot(WB), and the mRNA expression of NLRP3, PKCδ, pNLRC4, and IL-1Ra was detected by qRT-PCR. The results showed that compared with the blank control group, the VVC model group showed redness, edema, and white secretions in the vagina. Compared with the VVC model group, the BAEB groups showed improved general state of VVC mice. As revealed by Gram staining, Papanicolaou staining, microdilution assay, and HE staining, compared with the blank control group, the VVC model group showed a large number of hyphae, neutrophils infiltration, and increased fungal load in the vaginal lavage, destroyed vaginal mucosa, and infiltration of a large number of inflammatory cells. BAEB could reduce the transformation of C. albicans from yeast to hyphae. High-dose BAEB could significantly reduce neutrophil infiltration and fungal load. Low-and medium-dose BAEB could reduce the da-mage to the vaginal tissue, while high-dose BAEB could restore the damaged vaginal tissues to normal levels. ELISA results showed that the content of inflammatory cytokines IL-1β, IL-18, and LDH in the VVC model group significantly increased compared with that in the blank control group, and the content of IL-1β, IL-18 and LDH in the medium-and high-dose BAEB groups was significantly reduced compared with that in the VVC model group. WB and qRT-PCR results showed that compared with the blank control group, the VVC model group showed reduced protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues of mice and increased protein and mRNA expression of NLRP3. Compared with the VVC model group, the medium-and high-dose BAEB groups showed up-regulated protein and mRNA expression of PKCδ, pNLRC4, and IL-1Ra in vaginal tissues and inhibited protein and mRNA expression of NLRP3 in vaginal tissues. This study indicated that the therapeutic effect of BAEB on VVC mice was presumably related to the negative regulation of NLRP3 inflammasome by promoting PKCδ/NLRC4/IL-1Ra axis.

Advances in treatment and prognosis of MiT family translocated renal cell carcinoma / 中华泌尿外科杂志

MiT family translocation renal cell carcinoma mainly includes Xp11.2/TFE3 gene fusion-related renal cell carcinoma (TFE3 RCC)and t(6; 11)/TFEB gene fusion-related renal cell carcinoma(TFEB RCC), which is rare and there is no standard treatment plan yet, and the prognosis is still controversial. For localized lesions, surgery is the first choice for treatment, and systemic treatment such as targeted drugs and immune checkpoint inhibitors can be combined when there is metastasis. The application of gene testing provides the basis for personalized treatment. TFE3 RCC is highly invasive and has a poor prognosis, while TFEB RCC usually has a biological behavior of inertia and a better prognosis.

Clinicopathologic features and prognosis of Xp11.2/TFE3 gene fusion associated renal cell carcinoma in adults / 中华泌尿外科杂志

Objective:To investigate the clinicopathological features and prognosis of adult Xp11.2/TFE3 gene fusion-associated renal cell carcinoma (TFE3 RCC).Methods:The clinical data of 55 patients with TFE3 RCC admitted to the First Affiliated Hospital of Zhejiang University Medical College from January 2013 to February 2021 were retrospectively analyzed, including 26 males and 29 females. The patients’ mean age was (40.6 ± 14.7) years. The median tumor size was 4.0 (1.9-20.0) cm. Tumors were located in the left kidney in 30 cases (54.5%) and the right kidney in 25 cases (45.5%). Preoperative imaging assessment was well-circumscribed in 41 patients (74.5%) and ill-defined in 14 patients (25.5%). There were 2 cases of regional lymph node metastasis and 2 cases of distant metastasis, including 1 case of lung metastasis and 1 case of bone metastasis. Preoperative staging included stage I in 38 patients (69.1%), stageⅡ in 5 patients (9.1%), stage Ⅲ in 9 patients (16.4%), and stageⅣin 3 patients (5.5%). Nephron-sparing surgery was performed in 31 patients (56.4%) and radical nephrectomy in 24 patients (43.6%). Progression-free survival curves were plotted by the Kaplan-Meier method and analyzed by the log-rank test. Cox proportional hazards regression model was applied for multivariate analysis of factors influencing progression-free survival.Results:Postoperative pathological stage included pT 1 in 41 patients (74.5%), pT 2 in 5 patients (9.1%), pT 3 in 8 patients (14.5%), and pT 4 in 1 patient (1.8%). Four patients (7.3%) had N 1 stage and 2 (3.6%) had M 1 stage. After immunohistochemical analysis, TFE3 showed diffuse strong positive reaction in 55 patients, cathepsin K positive in 36 patients (65.5%), CD10 positive in 48 patients (87.3%), CK7 positive in 7 patients (12.7%), CA-IX positive in 2 patients (3.6%), and PAX8 positive in 35 patients (63.6%). Two cases were tested by fluorescent in situ hybridization (FISH), and the results were positive. The proportion of nuclei with mitotic signals was 40% and 30%, respectively. The median follow-up time was 27 (3-96) months. The results of survival analysis showed that the 3-year and 5-year progression-free survival rates were 80.0% and 64.0%, respectively. The results of univariate analysis showed that tumor size ( P = 0.009), pT stage ( P<0.001), regional lymph node invasion ( P = 0.003), and surgical approach ( P = 0.006) were associated with the prognosis of TFE3 RCC patients. Multivariate analysis of the Cox model was performed on significant univariate factors, and its results showed that pT stage ( HR=4.824, 95% CI 1.129-20.604, P=0.034) and regional lymph node invasion ( HR=5.522, 95% CI 1.066-28.611, P = 0.042) were independent prognostic factors for progression-free survival in TFE3 RCC patients. The results of stratified analysis showed that for patients with pT 1 disease, the effect of surgical approach on the prognosis of patients was not statistically significant ( P=0.091). The 3-year progression-free survival rates for nephron-sparing surgery and radical nephrectomy were 94.7% and 81.5%, respectively. Conclusions:Given that TFE3 RCC imaging studies often lack characteristic features, diagnosis mainly relies on immunohistochemical analysis and FISH tests. Most of the patients with TFE3 RCC have a better prognosis after surgical treatment. However, pT stage and regional lymph node invasion were prognostic factors in patients with TFE3 RCC.

Butyl alcohol extract of Baitouweng Decoction alleviates vulvovaginal candidiasis in mice by downregulating NLRP3 inflammasome and related signal pathways / 中国中药杂志

This study aims to explore the effect of butyl alcohol extract of Baitouweng Decoction(BAEB) on vulvovaginal candidiasis(VVC) in mice and to clarify the mechanism from Toll-like receptors(TLRs)/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome. To be specific, female KM mice were randomized into control group(i.g., normal saline), model group, fluco-nazole group(i.g., 20 mg·kg~(-1)), and low-dose, medium-dose, and high-dose BAEB groups(i.g., 20, 40, and 80 mg·kg~(-1), respectively). VVC was induced in mice except the control group. After the modeling, administration began and lasted 7 days. The ge-neral conditions and body weight of mice were recorded every day. On the 1 st, 3 rd, 7 th, and 14 th after vaginal infection by Candida albicans, the fungal load in the vaginal lavage fluid of the mice was measured with the plate method, and the morphology of C. albicans in vaginal lavage fluid was observed based on Gram staining. After the mice were killed, vaginal tissues were subjected to hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining for vaginal histopathological analysis. The content of cytokines in vaginal lavage fluid, such as interleukin(IL)-1β, IL-18, tumor necrosis factor-α(TNF-α), IL-6, and S100 a8, was determined by enzyme-linked immunosorbent assay(ELISA), and content of reactive oxygen species(ROS) in vaginal tissues by tissue ROS detection kit. The protein expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and nuclear factor-κB(NF-κB) in vaginal tissues was detected by Western blot, and the levels and distribution of NLRP3, Dectin-1, Syk, MyD88, TLR2, and TLR4 in vaginal tissues were determined with the immunohistochemical method. The results show that BAEB can improve the general conditions of VVC mice, reduce the fungal load and C. albicans hyphae in vaginal secretion, decrease ROS content in vaginal tissues and content of cytokines in vaginal lavage fluid, and down-regulate the expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and NF-κB in vaginal tissues. The above results indicate that BAEB exerts therapeutic effect on VVC mice by down-regulating the key proteins in the TLRs/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome.

Safety and efficacy of domestic single-port robotic surgery system for extraperitoneal urological surgery / 中华泌尿外科杂志

Objective:To investigate the safety and efficacy of the novel single-port surgical robotic surgical system in extraperitoneal urological surgery.Methods:From February to April 2022, patients was prospectively enrolled who required laparoscopic radical prostatectomy, partial nephrectomy and adrenal tumor resection in urology department. Inclusion criteria were: age ≥ 18 years old; BMI 18.5-30 kg/m 2; American Society of Anesthesiologists (ASA) physical status classification system grades 1 to 3; can cooperate with the completion of the visits and related examinations stipulated in the plan, and participate voluntarily clinical trials, and consent or the guardian agrees to sign the informed consent form; tumor indicators meet one of the following surgical treatment indications: kidney tumor T 1 stage, single, maximum tumor diameter ≤ 4 cm; prostate cancer, stage ≤ T 2b, preoperative PSA ≤ 20 ng /ml; Gleason score ≤ 7; adrenal tumor diameter ≤ 7 cm, for non-functioning adrenal adenoma, tumor diameter ≥ 3 cm. Exclusion criteria were: patients with other malignancies or a history of other malignancies and the investigators believe that they are not suitable for inclusion in this researcher; patients who have received the same type of urological surgery in the past and are not suitable for participating in this study as assessed by the investigators; included Those who have undergone other major surgery within the first 3 months and during the trial period, or who cannot recover from the side effects of any such surgery; syphilis, hepatitis B, HIV infection and carriers; long-term use of anticoagulants or blood system diseases; Unable to use effective contraception during the trial period and other conditions that the investigators deem inappropriate to participate in this trial. All operations were performed by a novel single-port robotic surgical operating system, and all surgical procedures were performed through an extraperitoneal approach. Surgical method: the surgical system is mainly composed of a remote console including a high-definition display, a surgical equipment trolley, a surgical execution system that accommodates a serpentine robotic arm, and a bendable serpentine robotic arm. In this study, the extraperitoneal approach was used. For radical prostatectomy, the patient was placed in a supine position, a longitudinal incision of about 3 cm was made below the umbilicus, the anterior rectus sheath was incised, the extraperitoneal space was separated, and an operating sheath was placed. A 12 mm trocar is placed between the right McBurney point and the umbilicus as an auxiliary hole. For partial nephrectomy and adrenal tumor resection, the patient is placed in the lateral position, and an 3cm incision is made 2 cm above the iliac crest on the midaxillary line as the main operating hole. The skin, subcutaneous tissue, and muscle were incised to the retroperitoneal cavity, and a 12mm trocar was placed at the level of the anterior superior iliac spine on the anterior axillary line as an auxiliary hole. The operation was performed after connecting each robotic arm. After the operation, the specimen was placed in the specimen bag, and a drainage tube is placed in the auxiliary hole, the specimen was taken out, and the incision was closed in turn. Preoperative basic information, operation time, blood loss, incision size, postoperative complications, preoperative and postoperative PSA score, eGFR index, postoperative pathological information and other perioperative information were collected. Results:A total of 17 patients were included in this study, including 6 with prostate cancer, 8 with renal tumor, and 3 with adrenal tumor. There were 9 males and 8 females, with an average age of (56.7±14.6) years and a BMI of (23.3±3.4) kg/m 2. The mean operation time of radical prostatectomy was (244.6±35.1) min, the mean operating time of the chief surgeon was (184.0±39.0) min, and the mean blood loss was (36.6±23.8) ml. Postoperative positive margin was found in 2 cases. The average operation time of partial nephrectomy was (189.6±49.4) minutes, the average operating time of the chief surgeon was (115±39.7) minutes, the average blood loss was (12.7±8.3) ml, and the average warm ischemia time was (23.1±10.8) minutes. There was no significant difference in the eGFR index before and after the operation ( P>0.05). The average operation time of adrenalectomy was (177.6±26.9) min, the average operating time of the chief surgeon was (99±20.4) min, and the average blood loss was (11.6±6.2) ml. The overall average operation time of the three surgical methods was (206.9±50.1) min, the overall average operating time of the chief surgeon was (136.5±51.1) min, the overall average blood loss was (21.0±9.2) ml, and the overall average incision size was (3.5±0.5) cm, all added a 12 mm auxiliary channel, and the overall average hospital stay was (8.1±2.7) days. All operations were successfully completed, and there was no conversion to open surgery during the operation, and no operation holes were added. There was no Clavien-Dindo≥grade 3 complication after operation. Conclusions:The novel single-port robot could safely and effectively perform radical prostatectomy, partial nephrectomy and adrenalectomy which are common in urology through extraperitoneal approach.

Construction and mechanism of dry eye model in mice with ocular surface iron overload / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish a dry eye mouse model of iron overload by intraperitoneal injection of iron dextran and preliminarily explore its possible mechanism.METHODS: A total of 40 male C57BL/6 mice(taking the right eye as the experimental eye)were divided into 4 groups by random number table method: There were 10 mice in the control group, each time by intraperitoneal injection of 0.2mL of normal saline; Low-dose group, middle-dose group and high-dose iron group with 10 mice in each group were the model group. Each time, 0.2mL of iron dextran solution with concentrations of 12.5, 25, and 50 mg/mL was injected intraperitoneally. One injection 3d for a total of 28d. We observed the ocular surface inflammation index, corneal fluorescein staining, tear break-up time(BUT)and Schimer I test(SIt)on the 7, 14 and 28d after injection and evaluated the degree of dry eye and ocular surface inflammation. After 28d, the mice were sacrificed for cornea, conjunctiva and lacrimal glands tissue for HE staining, Prussian blue staining and tissue iron detection, to evaluate the inflammatory reaction and iron overload. The expression of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and matrix metallo proteinase-9(MMP-9)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS: Compared with the control group, the mice in the model group showed a series of dry eye symptoms, the inflammation index of ocular surface in mice were increased, the score of corneal fluorescein staining increased, the BUT shortened and the amount of tear secretion decreased(all P&#x003C;0.05). The cornea, conjunctiva and lacrimal gland tissues of the mice were damaged to varying degrees, the iron deposition on the eye surface of the model group was more serious than that of the control group, and the iron content of the tissue was significantly increased than the control group(all P&#x003C;0.01). The contents of inflammatory factors(IL-1β, TNF-α, MMP-9)in the cornea, conjunctiva and lacrimal gland tissue of the mice in the model group were significantly higher than those of the control group(all P&#x003C;0.01). With the increase of injection time and concentration of iron dextran, the degree of dry eye and ocular surface inflammation in mice gradually increased. CONCLUSION: The mouse iron overload dry eye model was successfully established by intraperitoneal injection of iron dextran, the mechanism may be related to the ocular surface inflammation aggravated by iron overload.

Efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore whether efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization. METHODS: A total of 50 healthy C57BL/6 male mice aged 6-8wk were randomly divided into normal control group, iron group, inhibitor group, enhancer group and solvent control group, with 10 mice in each group. The normal control group was injected intraperitoneally with 0.2mL of normal saline, and the other groups were injected intraperitoneally with 50mg/mL iron dextran of 0.2mL, once every 3d. From the 14d, the inhibitor group, the enhancer group and the solvent control group were injected intraperitoneally with the same volume(0.2mL)50mg/kg XMD8-92, 10mg/kg simvastatin and 50% DMSO solvent once a day, respectively. The anterior segment of the eyes was observed under slit lamp microscope on the 7, 14, 28d after intraperitoneal injection, and the ocular surface inflammation index and corneal fluorescein staining score were evaluated. The cornea, conjunctiva and lacrimal gland tissues were taken at 28d for the HE staining and immunofluorescence staining, and RT-PCR were used to detect the expression of macrophage polarization related indexes(CD86, CD206, iNOS, Arg-1); Western blot were used to detect the expression of efferocytosis related signal factors(Gas6, MerTK); ELISA was used to detect the expression of inflammatory factors(IL-1β, TNF-α, MMP-9).RESULTS: After injection for 28d, compared with the normal control group, the ocular surface inflammatory index and corneal fluorescein staining score were increased in the iron group and the solvent control group. HE staining showed incomplete corneal epithelium, reduced conjunctival goblet cells, unclear lacrimal gland structure and relatively disordered arrangement of cells. In all tissues, the expressions of polarization related indexes of M1 macrophages such as CD86 and iNOS were up-regulated, while those of M2 macrophages such as CD206 and Arg-1 were down-regulated, and the expressions of inflammatory factors such as IL-1β, TNF-α and MMP-9 were up-regulated(all P&#x003C;0.05). Compared with the iron group and the solvent control group, the ocular surface inflammation index and corneal fluorescein staining score of the inhibitor group were further increased. HE staining showed obvious exfoliation of corneal epithelium, further decrease or even disappearance of conjunctival goblet cells, disorder of lacrimal gland structure and irregular arrangement of cells. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was down-regulated(all P&#x003C;0.05), the expression of polarization related indexes of M1 macrophages such as CD86 and iNOS and the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 were further up-regulated(all P&#x003C;0.05). But the ocular surface inflammation index and corneal fluorescein staining score decreased in the enhancer group. HE staining showed the integrity of corneal epithelial, the increase of conjunctival goblet cells and the improvement of lacrimal gland structure and morphology. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was up-regulated(all P&#x003C;0.05), and the expression of polarization related indexes of M2 macrophages such as CD206 and Arg-1 was up-regulated, while the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 was down-regulated(all P&#x003C;0.05). CONCLUSION: High-iron environment induces macrophages polarize to M1, which aggravates ocular surface inflammation and tissue damage. Efferocytosis by regulating the polarization of macrophages impact the occurrence of ocular surface inflammation in high-iron environment.

Effect and safety of fourth arm robot assisted partial nephrectomy via retroperitoneal approach / 中华泌尿外科杂志

Objective:To investigate the effect and safety of using the fourth arm in robot assisted partial nephrectomy via retroperitoneal approach.Methods:The clinical data of 480 patients with newly diagnosed renal tumors treated in the First Affiliated Hospital of Medical College of Zhejiang University from January 2016 to December 2018 were analyzed retrospectively. All patients underwent robot assisted partial nephrectomy with the fourth arm and were divided into two groups according to the surgical approaches. There were 312 cases in the retroperitoneal group, 198 males and 114 females, aged 18-82 years, with an average of 54.0 years. The tumors were located in the right kidney in 152 cases (48.7%), left kidney in 155 cases(49.7%), double kidney in 5 cases (1.6%), with tumor size of (3.5±2.7) cm, R.E.N.A.L. score of 4-5 in 105 cases (33.7%), 6-8 in 143 cases(45.8%), and 9-12 in 64 cases (20.5%). There were 168 cases in the transperitoneal group, 105 males and 63 females, the age ranged from 21 to 79 years, with an average of 53.2 years. The tumors were located in the right kidney in 85 cases (50.6%), left kidney in 78 cases (46.4%), double kidney in 3 cases (1.8%), with tumor size of (3.8±2.9) cm, R.E.N.A.L. score of 4-5 in 52 cases (31.0%), 6-8 in 81 cases (48.2%), and 9-12 in 35 cases (20.8%). In the retroperitoneal group, the patients were placed in the 90 ° lateral position on the healthy side, the lens hole cannula was placed 2-3 cm above the iliac crest, and one operation hole cannula was placed 8 cm away from the lens hole cannula on the ventral and dorsal sides respectively. The included angle between the two operation holes and the lens hole was 150°-180°. The fourth arm operation hole was established 8 cm away from the ventral operation hole, and the included angle between the connecting line and the horizontal line is ≤15°. The fourth arm operating hole was placed with ProGrasp forceps, which can be used to push away fat, peritoneum, traction and lift kidney, etc., so as to obtain satisfactory operating space and position. The perioperative conditions and surgical complications of the two groups were compared.Results:The operations were successfully completed in both groups, and there was no conversion to open surgery. The installation time of retroperitoneal group and transperitoneal group were (12.3±5.3)min and (7.8±3.8)min respectively, the console time was (70.5±17.1)min and (89.4±23.9)min respectively, the warm ischemia time was (17.3±8.2)min and (19.2±9.1)min respectively, the intraoperative bleeding volume was (115.2±47.3)ml and (125.8±52.1)ml respectively, and the intestinal recovery time was (1.5±1.8)d and (2.7±2.4)d respectively.The postoperative hospital stay was(6.3±1.8)d and (7.4±2.8)d, respectively ( P<0.05). The positive rates of incision margin in retroperitoneal group and transperitoneal group were 0(0 cases) and 0.6% (1 case). The time of indwelling drainage tube was (4.6±2.5)d and (4.9±2.8)d, respectively, and there was no significant difference ( P>0.05). The incidence of postoperative complications in the retroperitoneal group was lower than that in the transperitoneal group (67 cases, 21.5% vs. 51 cases, 30.3%, P=0.031). There was significant difference in the incidence of Clavien grade Ⅰ-Ⅱ complications (62 cases, 19.8% vs. 48 cases, 28.6%, P=0.030). There was no significant difference in the incidence of Clavien grade Ⅲ-Ⅳ complications (5 cases, 1.6% vs. 3 cases, 1.9%, P>0.05). Conclusions:Compared with the transperitoneal approach, the retroperitoneal approach with the fourth arm robot assisted partial nephrectomy is safe and effective, with shorter operation time, warm ischemia time, postoperative recovery time and fewer complications.

Treatment experience of a case of brodifacoum poisoning / 中国职业医学

OBJECTIVE: To analyze the experience of diagnosis and treatment of a case of brodifacoum poisoning. METHODS: The clinical data of a case of unexplained brodifacoum poisoning was retrospectively analyzed. RESULTS: The patient went to the doctor for unexplained bleeding. The bleeding symptoms included nasal o blood ozing, blood in saliva and skin ecchymosis. Blood anticoagulative rodenticide test showed positive with brodifacoum. The results of coagulative function tests showed that the indexes of partial prothrombin time, prothrombin time and fibrinogen were increased. The patient was diagnosed as brodifacoum poisoning based on the clinical symptoms and laboratory test results. The combined use of 40 mg/d of vitamin K_1 and frozen plasma improved the clotting time and quickly alleviated the bleeding symptoms of the patient. However, the patient′s bleeding symptoms recurred when vitamin K_1 was discontinued. The patient was hospitalized for 62 days and then discharged. With follow-up one month after discharge, the patient showed no bleeding symptoms, but brodifacoum could still be detected in the blood. CONCLUSION: The symptoms of brodifacoum poisoning may relapse and the treatment course is long. Vitamin K_1 could be used as the first-choice medicine for the treatment of brodifacoum poisoning, but its usage needs to be optimized.

Diagnostic Performance of ⁶⁸Gallium Labelled Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography and Magnetic Resonance Imaging for Staging the Prostate Cancer with Intermediate or High Risk Prior to Radical Prostatectomy: A Systematic Review and Meta-analysis

PURPOSE: To compare the diagnostic efficiency of ⁶⁸Gallium labelled prostate-specific membrane antigen positron emission tomography (⁶⁸Ga-PSMA PET) and magnetic resonance imaging (MRI) for staging the lymph node metastases (LNMs) in the prostate cancer.MATERIALS AND METHODS: A broad search of scientific databases including PubMed, EMBASE, Web of Science, Cochrane Database, and Chinese Biomedicine Literature Database (updated prior to November 1st, 2018) was conducted systematically by two reviewers. In this paper, we evaluated the methodological quality of each included article independently and performed a systematic review and meta-analysis to reveal the summary of the diagnostic performance of ⁶⁸Ga-PSMA PET and MRI in properly identifying LNMs of intermediate- and/or high-risk prostate cancer.RESULTS: Thirteen eligible articles comprising 1,597 patients were included. For LNMs detection, the pooled sensitivity and specificity of ⁶⁸Ga-PSMA PET were 0.65 (95% confidence interval [CI]: 0.49–0.79) and 0.94 (95% CI: 0.88–0.97), respectively, while the corresponding values of MRI were 0.41 (95% CI: 0.26–0.57) and 0.92 (95% CI: 0.86–0.95). The area under the symmetric receiver-operating characteristic (SROC) curve for ⁶⁸Ga-PSMA PET and MRI were 0.92 and 0.83, respectively.CONCLUSIONS: In intermediate- or high-risk pre-treatment prostate cancer, ⁶⁸Ga-PSMA PET had a higher sensitivity and a slightly different specificity in probing the LNMs when comparing with MRI. Moreover, the area under the SROC curve indicated that ⁶⁸Ga-PSMA PET was a more effective weapon for predicting the LNMs prior to radical surgery.

Serum microRNA expression profiling revealing potential diagnostic biomarkers for lung adenocarcinoma / 中华医学杂志(英文版)

BACKGROUND@#Recent studies have demonstrated that microRNAs (miRNAs) in the blood circulation can serve as promising diagnostic markers for cancers. This four-stage study aimed at finding serum miRNAs as potential biomarkers for lung adenocarcinoma (LA) diagnosis.@*METHODS@#The study was carried out between 2016 and 2017. The Exiqon miRNA qPCR panel (3 LA vs. 1 normal control [NC] pooled serum samples) was used for initial screening to acquire miRNA profiles. Thirty-five dysregulated miRNAs were further evaluated in the training (24 LA vs. 24 NCs) and testing stages (110 LA vs. 110 NCs) using quantitative real-time polymerase chain reaction assays.@*RESULTS@#Four serum miRNAs (miR-133a-3p, miR-584-5p, miR-10b-5p, and miR-221-3p) were significantly overexpressed in LA patients compared with NCs. The diagnostic value of the four-miRNA panel was validated by an external cohort (36 LA vs. 36 NCs). The areas under the receiver operating characteristic curve of the four-miRNA panel in the training, testing, and external validation stages were 0.734, 0.803, and 0.894 respectively. Meanwhile, the expression level of miR-221-3p was much higher in LA tumor samples than that in the adjacent normal tissues (19 LA vs. 19 NCs). The expression level of miR-10b-5p was also elevated in the serum-derived exosomes samples (18 LA vs. 18 NCs). The expression of miR-133a-3p, miR-584-5p, and miR-10b-5p was significantly elevated in LA patients with epidermal growth factor receptor mutation compared with NCs.@*CONCLUSION@#The study established a four-miRNA signature in serum that could improve the diagnostic capability of LA.

Clinical trial of acupuncture treatment of gastroesophageal reflux cough by needling dorsal segment of the Governor Vessel / 针刺研究

OBJECTIVE: To observe the curative effect of acupuncture stimulation of the back segment (10 spots below the spinous processes from T3 to T12) of the Governor Vessel in the treatment of gastroesophageal reflux cough (GERC). METHODS: A total of 60 cases of GERC patients were randomly divided into acupuncture and medication groups (n＝30 in each). For patients of the acupuncture group, the depression spots below the spinous processes from T3 to T12, including acupoints Shenzhu (GV12), Shendao (GV11), Lingtai (GV10), Zhiyang (GV9), Jinsuo (GV8) and non-acupoints (T4, T8, T12) were punctured with filiform needles, once every other day for 8 weeks. Patients of the medication group were ordered to take omeprazole capsules (20 mg/time), twice a day for 8 weeks. The therapeutic effect was assessed by using "Reflux Diagnostic Questionnaire"(RDQ, scores of symptoms of heartburn, retrosternal pain, acid regurgitation and food regurgitation, 0－40 points), cough symptom score (0－3 points) and "Leicester Cough Questionnaire" (LCQ, scores of physiological, psychological and social functions, 0－21 points), respectively. RESULTS: Following the treatment, RDQ score and cough symptom scores during both daytime and night were significantly decreased in both groups (P<0.05)，and the scores of physiological status, psychological health and social function of LCQ were significantly increased in both acupuncture and medication groups in comparison with their own pre-treatment (P<0.05). The therapeutic effect of acupuncture was markedly superior to that of medication in lowering RDQ score and cough symptom scores of daytime and night, and in raising LCQ scores of the physiological status, psychological health and social function (P<0.05). CONCLUSION: Acupuncture stimulation of the dorsal segment of the Governor Vessel is effective in improving clinical symptoms and living quality of GERC patients.

Therapeutic effect of acupuncture combined electrical stimulation on aged patients with post‐stroke de‐pression／ / 心血管康复医学杂志

To explore therapeutic effect of acupuncture combined electrical stimulation on aged patients with post‐stroke depression .Methods : A total of 78 patients with post‐stroke depression were randomly and equally divided into routine treatment group (received health education based on routine treatment ) and combined treatment group (received acupuncture combined low‐frequency electrical stimulation based on routine treatment group ).After four‐week treatment , score of Hamilton rating scale for depression (HAMD) and therapeutic effect were compared between two groups .Results : Compared with before treatment , there was significant reduction in HAMD score in two groups after treatment ;compared with routine treatment group after treatment , there was significant reduction in HAMD score [(19.72 ± 2. 04) scores vs.(14. 94 ± 1. 86) scores] in combined treatment group , P＝0. 001 all.To‐tal effective rate of combined treatment group was significantly higher than that of routine treatment group (87.18% vs.64.1%, P＝0.018).Conclusion : Acupuncture combined low‐frequency electrical stimulation possesses significant therapeutic effect on post‐stroke depression , which is worthy of clinical application .

Expression of Nod-like receptor protein 3 inflammasome in peripheral blood mononuclear cells of children with Kawasaki disease in the acute stage / 中国当代儿科杂志

OBJECTIVE@#To study the association of Nod-like receptor protein 3 (NLRP3) inflammasome with inflammatory response in the acute stage and coronary artery lesion (CAL) in children with Kawasaki disease (KD).@*METHODS@#A total of 42 children with KD who were hospitalized from January to October 2017 were enrolled as the KD group, among whom 9 had CAL (CAL group) and 33 had no CAL (NCAL group). Fifteen age- and gender-matched children with pneumonia and pyrexia were enrolled as the pneumonia-pyrexia group. Fifteen healthy children were enrolled as the healthy control group. Real-time PCR was used to measure the mRNA expression of NLRP3 inflammasome (NLRP3, ASC and caspase-1) in peripheral blood mononuclear cells. The Spearman rank correlation test was used to investigate the correlation of NLRP3 mRNA expression with serum levels of C-reactive protein, erythrocyte sedimentation rate, interleukin-6, interleukin-1β, procalcitonin, albumin and prealbumin.@*RESULTS@#The KD group had significantly higher mRNA expression of NLRP3, ASC and caspase-1 in the acute stage than the pneumonia-pyrexia and healthy control groups (P<0.05). The CAL group had significantly higher mRNA expression of NLRP3 than the NCAL group (P<0.05). NLRP3 mRNA expression was correlated with C-reactive protein, interleukin-6, interleukin-1β, and prealbumin levels in children with KD in the acute stage (r=0.449, 0.376, 0.427, and -0.416 respectively; P<0.05).@*CONCLUSIONS@#NLRP3 inflammasome may participate in inflammatory response in the acute stage and the development of CAL in children with KD.

Prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features / 中国当代儿科杂志

OBJECTIVE@#To investigate the prevalence of Bordetella pertussis infection in children with chronic cough and its clinical features.@*METHODS@#A total of 106 children who were treated at the outpatient service or hospitalized from January 1, 2016 to May 31, 2017 were enrolled. Their nasopharyngeal swabs and venous blood samples were collected for Bordetella pertussis culture, multiple PCR and serum anti-pertussis toxin antibody detection. According to these results, the children were divided into pertussis group with 26 children and control group with 80 children, and clinical features were analyzed for both groups. E-test stripes were used to determine the sensitivity of Bordetella pertussis strains to erythromycin, azithromycin, doxycycline, levofloxacin, sulfamethoxazole/trimethoprim and amoxicillin.@*RESULTS@#Of the 106 children with chronic cough, 26 (24.5%) were found to have Bordetella pertussis infection. There were no significant differences in the incidence rates of typical symptoms of pertussis between the pertussis and control groups (P>0.05). E-test showed that erythromycin and azithromycin had a minimal inhibitory concentration (MIC) of >256 mg/L against five Bordetella pertussis strains, while amoxicillin had an MIC of 0.5-1 mg/L.@*CONCLUSIONS@#The presence of Bordetella pertussis infection in children with chronic cough should be taken seriously by clinicians, and children with chronic cough and Bordetella pertussis infection may not have the typical symptoms of pertussis and are mainly manifested as chronic cough. Amoxicillin may be an alternative drug for macrolide-resistant Bordetella pertussis infection.

Expression and Function of miR-181b in Diffuse Large B Cell Lymphoma / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression and function of miR-181b in diffuse large B cell lymphoma (DLBCL).</p><p><b>METHODS</b>The lymphoid tissues of 124 patients with DLBCL examined and treated in our hospital from March 2010 to March 2012 were used as the DLBCL group. The healthy lympaid dissases in another 64 patients with non lymphaoma were selected as the control group. The expression levels of miR-181b in two groups were detected, and the expression levels of miR-181b in lymphoid tissues of DLBCL patients with different clinical features were compared. The survival of DLBCL patients with different levels of miR-181b expression was compared.</p><p><b>RESULTS</b>The relative expression level of miR-181b in lymph tissues of DLBCL patients was significantly higher than that in healthy lymphoid tissues (P<0.05). The higher the Ann Arbor staging was, the higher the relative expression of miR-181b was in lymphoid tissues (P<0.05), and the higher the IPI score was, the higher the relative expression of miR-181b was in lymphoid tissues (P<0.05). The 5-year survival rate of the patients with miR-181b low expression was significantly higher than that of patients with miR-181b high expression (P<0.05).</p><p><b>CONCLUSION</b>There are differences in the expression of miR-181b in lymphoid tissues of DLBCL patients with different clinical stages and prognosis. It may become an effective indicator for the diagnosis and prognosis evaluation of DLBCL.</p>

Utility of the third arm in robot-assisted laparoscopic partial nephrectomy for complex renal tumor / 中华泌尿外科杂志

Objective To assess the safety and feasibility of utility of the third arm in robotic partial nephrectomy(RPN) through retroperitoneal approach for complex renal tumor.Methods 36 roboticassisted partial nepbrectomy were performed by one surgeon between November 2015 and January 2017,including hilar tumors in 12 cases,central tumors in 11 cases,endophytic tumors in 7 cases and multiple tumors in 6 cases.A 12 mm camera port is placed 2 fingerbreadth above iliac crest.The lateral and medial robotic trocars are placed in the posterior axillary line and anterior axillary plane respectively parallel to the cameraport trocar.Under direct visualization,the peritoneum is swept medially towards the paramedianplane.The fourth arm trocar is placed in the most medial and inferior aspect of the field approximately 7 cm to 8 cm across and parallel to the medial robotic trocar.Descriptive statistics on patient characteristics,operative parameters,and oncologic outcomes are analyzed.Result The 4-arms retroperitoneal approach was used in all patients without any conversion.Mean console time was 127 ± 21 (98-357) min.Mean ischemia time was 25.5 ± 8.3 (12-38) min,Mean estimated blood lost was 198 ± 201.5 (50-510) ml.No patients required blood transfusion,except one case underwent selective intra-arterial embolization with DSA (digital subtraction angiography) and blood transfusion post-operatively.Pathology revealed renal cell carcinoma in 12 patients,angiomyolipoma in 16 patients,chromophobe renal cell carcinoma in 6 cases,oncocytoma in 2 cases and all had negative surgical margins.Under 3 months follow-up,Mean decrease in eGFR was 4.3 ml/(min · 1.73m2).No patients found recurrence or metastasis.Conclusions The third robotic arm provides the console surgeon maximal independence from the surgical assistant when performing kidney retraction,ligation or clamping of renal hilar vessels in complex renal morbidities.It would be beneficial for patient with merits of retroperitoneal approach and overcomes limited space during RPN.

The posterior approach of robot-assisted laparoscopic radical prostatectomy / 中华泌尿外科杂志

Objective To explore the feasibility and safety of the posterior approach of robotassisted laparoscopic radical prostatectomy and to the approach.Methods From November 2001 to April 2017,32 patients underwent posterior approach of robot-assisted laparoscopic radical prostatectomy.Patients aged 53 to 81 years,with mean of 66.9 years old.Their prostate volumes were 12.0-73.7 ml with an average of 32.9 ml.All patients were diagnosed by prostate biopsy before surgery.The operation time,blood loss and length of hospital stay were recorded.Results All the operations were completed by robotic assisted laparoscopy with no transition to open surgery.The surgery time was 129-210 minutes with an average of 163.6 minutes.The estimated blood loss was 20-200 ml with an average of 59.3 ml.The hospital stay was 8-21 days with an average of 12.8 days.The postoperative hospital stay was 3-13 days with an average of 6.9 days.The time of postoperative catheter removal was 4-14 days with an average of 7.5 days.Postoperative follow-up was 1-6 months.Twenty-four (75％) patients had early recovery of continence,and all (100％) patients regained continence 3-month postoperatively.Conclusion The posterior approach of robotic assisted laparoscopic radical prostatectomy was a safe and effective surgical technique,which was beneficial in early continence recovery.

MECP2 duplication syndrome: a clinical analysis of three cases and literature review / 中国当代儿科杂志

MECP2 duplication syndrome (MDS) is a rare pediatric disease and mainly manifests as delayed motor development, language loss or delay, recurrent infection, severe intellectual disability, epilepsy, autistic symptoms, and early infantile hypotonia. In this article, the three children with this disease were all boys. Cases 1 and 2 had delayed motor development, and language loss or delay as initial manifestations, and case 3 had recurrent infection as initial manifestation. Physical examination showed hypotonia and negative pathological signs in each case. Case 1 had tonic-clonic seizures and electroencephalography showed focal seizures, for which he was given oxcarbazepine, levetiracetam, and clonazepam as the antiepileptic treatment to control seizures. Case 3 experienced one absence seizure and three head-nodding seizures with normal electroencephalographic findings during these seizures, and therefore, he was not given antiepileptic treatment. In each case, recurrent infection was improved with the increase in age, but there were no significant improvements in language or intelligence. Array-based comparative genomic hybridization (aCGH) showed MECP2 duplication in X chromosome in each case, and so they were diagnosed with MDS. MDS should be considered for children with delayed development complicated by recurrent infection and epileptic seizures, and early aCGH helps with the diagnosis of this disease.

Recent progress in clinical research on pertussis / 中国当代儿科杂志

Pertussis is a highly contagious respiratory disease. Despite the high vaccination coverage, re-emergence of pertussis has been reported in many countries over the past two decades. With the increase in the incidence of pertussis, there has been a shift in the epidemiological features: an increased incidence of pertussis has been noted in older children and adults, who normally lack typical clinical manifestations, and who may be easily missed according to current diagnostic references for pertussis. In order to achieve better prevention and treatment of pertussis, this review article summarized the recent research progress in the epidemiology, clinical features, etiology, diagnosis, treatment, and prevention of pertussis, particularly focusing on the diagnosis of pertussis in older children and adults.