Risk factors of hepatocellular carcinoma to TACE refractoriness / 中华肝胆外科杂志

Objective:To study the risk factors of patients with hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization(TACE) refractoriness.Methods:The clinical data of 106 HCC patients who underwent TACE at the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively studied. There were 90 males and 16 females, with the age of (59.9±9.3) years. These patients were divided into the TACE-refractory group ( n=47) and the control group ( n=59) based on whether TACE refratoriness occurred after surgery. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVIKA-II), maximum diameter of tumor, number of tumor and tumor vascularization patterns between the two groups were compared. Multivariate logistic regression analysis was performed to analyse the risk factors of TACE refractoriness in patients with HCC after TACE. Results:The proportion of patients with AFP >400 μg/L, PIVIKA-II >40 AU/L, number of tumor and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement) were significantly higher in the TACE-refractory group than the control group (all P<0.05). The maximum diameter of tumor for patients in the TACE-refractory group was significantly larger than that in the control group ( Z=-2.41, P=0.016). Multivariate logistic regression analysis showed that patients with serum AFP >400 μg/L( OR=2.707, 95% CI: 1.008-7.271), multiple tumors ( OR=6.069, 95% CI: 2.115-17.415) and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement)( OR=7.813, 95% CI: 2.246-27.176) before the first TACE were at increased risks of TACE refractoriness (all P<0.05). Conclusion:Preoperative AFP >400 μg/L, multiple tumors and tumor vascularization patterns Ⅲ+ Ⅳ were independent risk factors for TACE refractoriness in patients with HCC.

Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with anterior cruciate ligament injury / 中华创伤杂志

Objective:To explore the clinical outcomes of intraoperative fluoroscopy on femoral tunnel placement in treating professional snow sports athletes with anterior cruciate ligament (ACL) injury.Methods:A retrospective case series study was used to analyze the clinical data of 13 professional snow sports athletes with ACL injury treated in the National Institute of Sports Medicine, General Administration of Sport of China from January 2016 to January 2019. There were 5 males and 8 females, aged 16-27 years [(18.5±3.0)years]. Intraoperative lateral fluoroscopy combined with quadrant method was performed for the accurate femoral tunnel placement in single-bundle ACL reconstruction by using autologous hamstring tendon in all patients. KT1000 side-to-side difference (KT1000-ssd), pivot shift test, International Knee Documentation Committee (IKDC) subjective score, Lysholm score, Marx activity scale and maximum extension and flexion resistance ratio of the involved and uninvolved knee were compared before operation (or before injury) and at 3, 6, 12 and 24 months after operation. Whether returning to the field, time taken in returning to the field and re-injury were recorded at each follow-up visit. ACL graft signal intensity ratio (SIR) in MRI of the involved knee was evaluated at postoperative 24 months.Results:All patients were followed up for 24-33 months [(25.8±2.7)months]. There were 7 patients with KT1000-ssd degree I, 5 with degree II and 1 with degree III before operation, compared to 12 patients with KT1000-ssd degree 0 and 1 with degree I at 3 and 6 months after operation and 13 patients with KT1000-ssd degree 0 at 12 and 24 months after operation. The pivot shift test was grade I in 8 patients and grade II in 5 before operation, compared to 11 patients with degree 0 and 2 with degree I at 3 months after operation and 12 patients with degree 0 and 1 with degree I at 6, 12 and 24 months after operation. IKDC subjective score was (68.0±4.3)points, (84.7±7.9)points, (94.6±3.3)points and (96.5±1.8)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, IKDC subjective score was significantly improved compared to the preoperative (48.3±25.0)points (all P<0.01). The Lysholm score was (63.4±6.6)points, (80.1±6.5)points, (93.8±4.6)points and (96.5±2.4)points at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the Lysholm score was significantly improved compared to the preoperative (47.5±29.4)points (all P<0.01). The Marx activity scale was (7.4±0.5)points, (13.8±0.7)points, (14.6±0.8)points and (15.0±0.7)points at postoperative 3, 6, 12 and 24 months, respectively, significantly lower than (16.0±0.0)points before the injury (all P<0.01). The maximum extension resistance ratio of the involved and uninvolved knee was 0.60±0.10, 0.85±0.08, 0.91±0.06 and 0.97±0.04 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum extension resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.57±0.18 (all P<0.01).The maximum flexion resistance ratios of involved and uninvolved knee were 0.64±0.09, 0.82±0.06, 0.89±0.04 and 0.94±0.06 at postoperative 3, 6, 12 and 24 months, respectively. Six months after operation, the maximum flexion resistance ratio of the involved and uninvolved knee was significantly increased compared to the preoperative 0.60±0.12 (all P<0.01). Thirteen athletes returned to the field within 12 months after operation with the time taken in returning to the field ranging from 5-12 months [(8.7±1.9)months]. There was no ACL re-injury at postoperative 24 months. The ACL graft SIR in MRI of the involved knee was 1.80±0.20 at postoperative 24 months. Conclusion:Intraoperative fluoroscopy on femoral tunnel placement in the treatment of professional snow sports athletes with ACL injury can significantly improve the knee joint stability, subjective function, sports performance and muscle strength within 6 months, and can help them return to the field within 12 months, and accelerates graft healing.

The clinical efficacy of all-port robotic versus thoracoscopic lobectomy in stageⅠA non-small cell lung cancer: A retrospective cohort study / 中国胸心血管外科临床杂志

@#Objective    To investigate the perioperative efficacy and safety of all-port robotic lobectomy versus thoracoscopic lobectomy in stageⅠA non-small cell lung cancer. Methods    The clinical data of patients with stageⅠA non-small cell lung cancer who underwent lobectomy with lymph node dissection performed by the same operator in our center from June 2019 to June 2022 were retrospectively analyzed. The patients were divided into a robotic group and a thoracoscopic group according to different procedures. We compared the relevant indexes such as operation time, intraoperative bleeding, number of lymph node dissection stations, number of lymph node dissection, postoperative tube time, postoperative hospitalization time, closed chest drainage volume, postoperative pain, postoperative complications and hospitalization cost between the two groups. Results    There were 83 patients in the robotic group, including 34 males and 49 females with a median age of 60.0 (53.0, 67.0) years, and 94 patients in the thoracoscopic group, including 36 males and 58 females with a median age of 60.5 (54.0, 65.3) years. There was no conversion to thoractomy or death in postoperative 90 days in both groups. No statistical difference was seen in the operation time, total postoperative drainage volume and postoperative complication rates between the two groups (P>0.05). Patients in the robotic group had less intraoperative bleeding (P<0.001), more lymph node dissection stations (P=0.002) and numbers (P=0.005), less postoperative pain (P=0.002), and shorter postoperative time with tubes (P=0.031) and hospital stay (P<0.001). However, the surgery was more expensive in the robotic group (P<0.001). Conclusion    All-port robotic surgery is safe and effective for patients with early-stage non-small cell lung cancer with less intraoperative bleeding, more lymph node dissection, less postoperative pain, and shorter hospital stay compared with the thoracoscopic surgery.

Analysis of the incidence of venous thromboembolic disease in urological inpatients during perioperation / 中华泌尿外科杂志

Objective:To investigate the incidence of venous thromboembolic disease (VTE) in urological inpatients during perioperation.Methods:The clinical data of 7 988 inpatients admitted to the Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January to December 2019 were analyzed retrospectively. The cohort included 5 657 males and 2 331 females. The average age of the enrolled patients was (56.3±15.8) years old, and the body mass index was (23.8±3.2) kg/m 2. There were 1 628 malignant tumors patients and 6 360 non-malignant tumors patients in the cohort. Of all the patients, 7 725 cases received surgical treatment. All patients were scored with the Caprini Risk Assessment Model (2005) after admission and 1 655 cases were classified as very low risk, 2 940 cases were low risk, 2 922 cases were medium risk, 345 cases were high risk and 126 cases were very high risk. Patients with Caprini score ≥ 2 and/or clinical symptoms were examined by venous color Doppler ultrasound. CT pulmonary angiography was performed for patients with chest pain, chest tightness, decreased blood oxygen saturation and other symptoms suspected of pulmonary embolism according to clinical judgment to screen the incidence of VTE. Results:Among the 7 988 cases, 180 cases (2.25%, 180/7 988) with VTE were found by preoperative examination, including 1 case (0.01%, 1/7 988) with pulmonary embolism. There were 199 new cases with VTE after operation, and the incidence of new VTE after operation was 2.58% (199/7 725). Among them, pulmonary embolism was found in 7 cases, with a incidence of 0.09% (7/7 725). Only 7.92% (30/379) of the VTE patients had VTE-related symptoms. The operations with higher incidence of VTE were radical cystectomy, nephroureterectomy, radical prostatectomy and radical nephrectomy, with the incidence of 11.61% (13/112), 10.87 (10/92), 8.25% (16/194) and 6.16% (22/357) respectively.Conclusions:The incidence of VTE in hospitalized patients with urinary surgery in this study is much higher than previously reported. Most of the patients with VTE are asymptomatic. The operations with high incidence of VTE after operation are radical cystectomy, nephroureterectomy, radical prostatectomy and radical nephrectomy. Therefore, it is necessary to carry out VTE screening for hospitalized patients in urology department, which is helpful to realize early intervention of VTE and reduce the risk of VTE progression and pulmonary embolism.

Automatic radiolabeling of the norepinephrine transporter targeted tracer 18F-mFBG and evaluation of 18F-mFBG PET/CT imaging in pheochromocytoma / 中华核医学与分子影像杂志

Objective:To fulfill the automatic radiolabeling of the norepinephrine transporter (NET) trancer 18F-meta-fluorobenzylguanidine (mFBG), and explore the 18F-mFBG PET/CT imaging effect of pheochromocytoma. Methods:On the basis of the chemical structure of mFBG, a spirocyclic iodonium ylide was used as the precursor to undergo a 3-step reaction sequence (radiofluorination, deprotection and neutralization) on AllinOne synthesis module. Purification by high performance liquid chromatography and formulation were conducted to generate 18F-mFBG. The corresponding quality control tests of 18F-mFBG product was performed. Afterwards, a postoperative patient with pheochromocytoma underwent 18F-mFBG PET/CT imaging. Results:The radiosynthesis was accomplished within 70 min, and 18F-mFBG was obtained in (17.8±2.4)% non-decay-corrected radiochemical yield ( n=5), with radiochemical purity >97% and molar activity >59.2 GBq/μmol. Sterility test, bacterial endotoxins test, abnormal toxicity test and the acetonitrile residue all met the requirements of Pharmacopoeia of the People′ s Republic of China (2020 Volume Ⅳ). The 18F-mFBG PET/CT imaging disclosed high uptake in pheochromocytoma and clear localization of lesions. Conclusions:The automatic radiolabeling of the NET targeted tracer 18F-mFBG is successfully realized by commercially available synthesis module, and the production quality meets all requirements for clinical translation. 18F-mFBG has a potential to image neuroendocrine lesions in clinical setting.

Curative effect of full-femtosecond small incision lenticule extraction on the treatment of high myopia based on propensity score matching / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the effect of full-femtosecond small incision lenticule extraction(SMILE)on the treatment of high myopia based on propensity score matching.METHODS: A total of 48 cases(48 eyes)of high myopia patients who underwent SMILE surgery in our hospital from May 2019 to May 2021 were selected as the observation group, and 48 cases(48 eyes)of high myopia patients who underwent FS-LASIK surgery were matched using propensity score matching as the control group. Follow up for 6mo after surgery, the changes in cylindrical, central corneal thickness, uncorrected visual acuity(UCVA), corneal endothelial cell related indicators [percentage of hexagonal endothelial cells(6A), coefficient of variation(CV)of endothelial cell area, central corneal endothelial cell density(ECD)] and corneal biomechanical indicators [simulated Goldman intraocular pressure(IOPg), corneal hysteresis(CH), corneal resistance factor(CRF), corneal compensated intraocular pressure(IOPcc)] between the two groups were compared, and the incidence of complications in both groups of patients was recorded.RESULTS: Both groups of patients showed significant improvements in cylindrical and UCVA at 3 and 6mo after surgery, as well as decreased central corneal thickness, corneal endothelial cells, and corneal biomechanics related indicators. The changes in the observation group were more significant(all P&#x003C;0.05). During the follow-up period, there was no significant difference in the incidence of complications between the observation group and the control group(8% vs. 17%, P&#x003E;0.05).CONCLUSION: SMILE has a definite effect on patients with high myopia and is helpful to improve visual acuity.

Study on the correlation between meibomian gland dysfunction and sleep quality / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To study the correlation between meibomian gland dysfunction(MGD)patients and their sleep quality.METHODS: Retrospective case-control study. A total of 150 MGD patients treated in our hospital from January 2021 to October 2022 were selected and divided into sleep disorder group(75 cases, PSQI&#x003E;10 points)and control group(75 cases, PSQI≤10 points)according to the Pittsburgh sleep quality index(PSQI). Both groups were scored using the ocular surface disease index(OSDI), underwent meibomian gland-related examinations(eyelid margin morphology, meibomian gland secretion ability, meibomian gland secretion quality score), corneal fluorescein staining(FL)score, Schirmer Ⅰ test(SⅠt), tear film break-up time(BUT)was measured, and sleep indicators(sleep quality, sleep latency, subjective sleep quality, sleep time)were evaluated.RESULTS: There were significant differences in OSDI score, FL score, SⅠt, BUT, eyelid margin morphology score, meibomian gland secretion ability score, and meibomian gland secretion quality score between the two groups(P&#x003C;0.05). In the sleep disorder group, PSQI score, sleep latency score, subjective sleep quality score, and sleep time score were significantly positively correlated with OSDI score, FL score, meibomian gland secretion ability score, and meibomian gland secretion quality score(P&#x003C;0.05); PSQI score, subjective sleep quality score, and sleep time score were significantly positively correlated with eyelid margin morphology score(P&#x003C;0.05); PSQI score, sleep latency score, and subjective sleep quality score were significantly negatively correlated with BUT and SⅠt(P&#x003C;0.05); sleep time score was significantly negatively correlated with BUT(P&#x003C;0.05); sleep latency score was not significantly correlated with eyelid margin morphology score(P&#x003E;0.05); sleep time score was not significantly correlated with SⅠt(P&#x003E;0.05).CONCLUSION:The ocular surface condition of MGD patients is correlated with multiple sleep quality indicators, and a decline in sleep quality may increase the risk of MGD.

Analysis of refractive parameters and theirs correlation with spherical equivalent in preschool children aged 3 to 6 years / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the distribution of refractive parameters and theirs correlation with spherical equivalent(SE)in preschool children aged 3 to 6 years, and evaluate the accuracy of each screening index in diagnosing refractive errors.METHODS: Cross-sectional study. A total of 791 preschool children, ranging from 3 to 6 years old, who consented to undergo mydriatic refraction were selected. Axial length(AL), corneal refractive power(K), and SE were measured after microcoria optometry and mydriatic optometry. Additionally, the corneal radius of curvature(CR)and the axial length/corneal radius of curvature(AL/CR)ratio were calculated.RESULTS: A total of 791 students participated in the study, out of which 400(50.6%)were male and 391(49.4%)were female. The mean values for AL, CR, AL/CR, and SE were 22.62±0.94mm, 7.81±0.29mm, 2.90±0.09, and +1.95±1.31D, respectively. AL, CR, and AL/CR increased with age. AL and CR were significantly higher in males than in females(all P&#x003C;0.001), while there was no statistically significant difference between AL/CR and SE in males and females(P=0.82, 0.19). The correlation coefficients of SE and AL/CR, AL and CR were -0.86, -0.50 and 0.16, respectively. The results of multiple linear regression analysis indicate that for each unit increase in AL/CR, there was a corresponding shift of 10.91 towards myopia in SE. The sensitivity of AL/CR in screening for myopia was 94.44%, with a specificity of 90.46% and a Youden index of 0.84. For screening myopia under microcoria optometry, the sensitivity was 100%, with a specificity of 66.09% and a Youden index of 0.66. The area under the curve was 0.967 and 0.809 when the ROC curves were plotted using AL/CR and AL as indicators for screening myopia, respectively.CONCLUSION: For large group screening activities where mydriatic optometry is not feasible, AL/CR is better for evaluating refractive status and identifying children with myopia and hyperopia reserve that are lower than normal for their age, compared to AL and microcoria optometry.

Risk factors of bortezomib-related peripheral neuropathy and the clinical features and electrophysiological characteristics of patients during treatment of multiple myeloma / 白血病·淋巴瘤

Objective:To explore the risk factors of bortezomib-related peripheral neuropathy (BIPN) and the clinical and electrophysiological characteristics of patients in treatment of multiple myeloma (MM).Methods:The clinical data of 71 newly diagnosed MM patients treated with BD (bortezomib + dexamethasone) regimen in Yancheng First People's Hospital from March 2016 to December 2019 were retrospectively analyzed. The bone marrow morphology, immunology, cytogenetics, molecular biology (MICM), routine electrophysiological examination before and after treatment were performed. All patients were divided into the peripheral neuropathy (PN) group and the non-PN group according to the presence or not of BIPN, and the clinicopathological differences of both groups were also compared; a binary logistic regression model was used to analyze the factors affecting the occurrence of PN. The electrophysiological characteristics were summarized and fluorescence in situ hybridization (FISH) was used to detect karyotype of BIPN patients.Results:Among 71 MM patients, there were 40 cases (56.3%) of PN and 31 cases (43.7%) of non-PN. The proportion of patients at international staging system (ISS) staging Ⅲ, and the levels of IgA, IgG, IgM, serum creatinine, β 2-microglobulin (β 2-MG) in the PN group were higher than those in the non-PN group, and hemoglobin (Hb) level in the PN group was lower than that in the non-PN group, and the differences were statistically significant (both P < 0.05). Binary logistic regression analysis showed that increased IgA ( OR = 1.151, 95% CI 1.012-1.309, P = 0.033), increased IgG ( OR = 1.055, 95% CI 1.000~1.112, P = 0.049), increased IgM ( OR = 1.010, 95% CI 1.001-1.018, P = 0.022), increased serum creatinine ( OR = 1.037, 95% CI 1.011~1.065, P = 0.005), increased β 2-MG ( OR = 1.564, 95% CI 1.039-2.354, P = 0.032) were risk factors for BIPN. Among 40 patients with BIPN, 33 cases (82.5%) of sensory nerve conduction velocity (SCV) were abnormal, 23 cases (57.5%) of motor nerve conduction velocity (MCV) were abnormal; 31 cases (77.5%) showed demyelination damage, 9 cases (22.5%) had axonal damage. Among 40 patients with BIPN, 24 cases underwent FISH detection, including 19 cases (79.2%) with chromosomal mutations, of which 12 cases (50.0%) were mixed subtype abnormal. Conclusions:MM patients with high levels of β 2-MG, IgA, IgG, IgM and serum creatinine are more prone to PN when treated with bortezomib. The electrophysiology of patients with BIPN is mainly characterized by demyelination of sensory nerves.

Analysis of the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019 / 中华劳动卫生职业病杂志

Objective: To analyze the burden of disease attributable to high temperature exposure in China and globally from 1990 to 2019, and to study the current burden of disease in relevant populations. Methods: In October 2021, based on data from the global burden of disease 2019 (GBD 2019) study, population attributable fraction (PAF), number of deaths, mortality, disability-adjusted life year (DALY) and DALY rate of Chinese and global populations with different ages and genders in 1990 and 2019 were extracted and analyzed. The rate of change was calculated, the mortality rate was normalized by the age structure of the world standard population, and the causes of disease burden caused by high temperature exposure of Chinese residents were analyzed. Results: In 2019, compared with 1990, the PAF of Chinese and global population decreased by 43.98% and 12.41% respectively, the number of deaths increased by 29.55% and 49.40% respectively, the crude mortality rate increased by 7.81% and 3.30% respectively, the DALY decreased by 48.12% and 14.41% respectively, and the DALY rate decreased by 56.82% and 40.82% respectively. The mortality rate of the ≥70 age group was higher than that of other groups. The disease burden indicators such as PAF, standardized mortality and DALY attributable to high temperature exposure in men were higher than those in women. In 2019, the main cause of DALY affected by high temperature exposure in Chinese population was ischemic heart disease (84400 person-years), and the main cause of death was ischemic heart disease (4900 cases). Conclusion: The burden of diseases attributable to high temperature exposure is still serious in China and the world at large. Targeted interventions should be formulated for men, the elderly and people with occupational exposure, and a sound surveillance system should be established to reduce the burden of diseases caused by high temperature exposure.

Research progress on pathogenesis and treatment of drug-resistant epilepsy / 药学学报

Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.

Bombyx Batryticatus extract promotes microglia polarization to improve neuron injury and behaviors of cerebral ischemia/reperfusion rats / 中国中药杂志

This study aims to investigate the effect of Bombyx Batryticatus extract(BBE) on behaviors of rats with global cerebral ischemia reperfusion(I/R) and the underlying mechanism. The automatic coagulometer was used to detect the four indices of human plasma coagulation after BBE intervention for quality control of the extract. Sixty 4-week-old male SD rats were randomized into sham operation group(equivalent volume of normal saline, ip), model group(equivalent volume of normal saline, ip), positive drug group(900 IU·kg~(-1) heparin, ip), and low-, medium-, and high-dose BBE groups(0.45, 0.9, and 1.8 mg·g~(-1)·d~(-1) BBE, ip). Except the sham operation group, rats were subjected to bilateral common carotid artery occlusion followed by reperfusion(BCCAO/R) to induce I/R. The administration lasted 7 days for all the groups. The behaviors of rats were examined by beam balance test(BBT). Morphological changes of brain tissue were observed based on hematoxylin-eosin(HE) staining. Immunofluorescence method was used to detect common leukocyte antigen(CD45), leukocyte differentiation antigen(CD11b), and arginase-1(Arg-1) in cerebral cortex(CC). The protein expression of interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-6(IL-6), and interleukin-10(IL-10) was detected by enzyme-linked immunosorbent assay(ELISA). The non-targeted metabonomics was employed to detect the levels of metabolites in plasma and CC of rats after BBE intervention. The results of quality control showed that the BBE prolonged the activated partial thromboplastin time(APTT), prothrombin time(PT), and thrombin time(TT) of human plasma, which was similar to the anticoagulation effect of BBE obtained previously. The results of behavioral test showed that the BBT score of the model group increased compared with that of the sham operation group. Compared with the model group, BBE reduced the BBT score. As for the histomorphological examination, compared with the sham operation group, the model group showed morphological changes of a lot of nerve cells in CC. The nerve cells with abnormal morphology in CC decreased after the intervention of BBE compared with those in the model group. Compared with the sham operation group, the model group had high average fluorescence intensity of CD45 and CD11b in the CC. The average fluorescence intensity of CD11b decreased and the average fluorescence intensity of Arg-1 increased in CC in the low-dose BBE group compared with those in the model group. The average fluorescence intensity of CD45 and CD11b decreased and the average fluorescence intensity of Arg-1 increased in medium-and high-dose BBE groups compared with those in the model group. The expression of IL-1β and IL-6 was higher and the expression of IL-4 and IL-10 was lower in the model group than in the sham operation group. The expression of IL-1β and IL-6 was lower and the expression of IL-4 and IL-10 was higher in the low-dose, medium-dose, and high-dose BBE groups than in the model group. The results of non-targeted metabonomics showed that 809 metabolites of BBE were identified, and 57 new metabolites in rat plasma and 45 new metabolites in rat CC were found. BBE with anticoagulant effect can improve the behaviors of I/R rats, and the mechanism is that it promotes the polarization of microglia to M2 type, enhances its anti-inflammatory and phagocytic functions, and thus alleviates the damage of nerve cells in CC.

Effects of total ginsenosides from Panax ginseng stems and leaves on gut microbiota and short-chain fatty acids metabolism in acute lung injury mice / 中国中药杂志

This study aimed to investigate the biological effects and underlying mechanisms of the total ginsenosides from Panax ginseng stems and leaves on lipopolysaccharide(LPS)-induced acute lung injury(ALI) in mice. Sixty male C57BL/6J mice were randomly divided into a control group, a model group, the total ginsenosides from P. ginseng stems and leaves normal administration group(61.65 mg·kg~(-1)), and low-, medium-, and high-dose total ginsenosides from P. ginseng stems and leaves groups(15.412 5, 30.825, and 61.65 mg·kg~(-1)). Mice were administered for seven continuous days before modeling. Twenty-four hours after modeling, mice were sacrificed to obtain lung tissues and calculate lung wet/dry ratio. The number of inflammatory cells in bronchoalveolar lavage fluid(BALF) was detected. The levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α) in BALF were detected. The mRNA expression levels of IL-1β, IL-6, and TNF-α, and the levels of myeloperoxidase(MPO), glutathione peroxidase(GSH-Px), superoxide dismutase(SOD), and malondialdehyde(MDA) in lung tissues were determined. Hematoxylin-eosin(HE) staining was used to observe the pathological changes in lung tissues. The gut microbiota was detected by 16S rRNA sequencing, and gas chromatography-mass spectrometry(GC-MS) was applied to detect the content of short-chain fatty acids(SCFAs) in se-rum. The results showed that the total ginsenosides from P. ginseng stems and leaves could reduce lung index, lung wet/dry ratio, and lung damage in LPS-induced ALI mice, decrease the number of inflammatory cells and levels of inflammatory factors in BALF, inhibit the mRNA expression levels of inflammatory factors and levels of MPO and MDA in lung tissues, and potentiate the activity of GSH-Px and SOD in lung tissues. Furthermore, they could also reverse the gut microbiota disorder, restore the diversity of gut microbiota, increase the relative abundance of Lachnospiraceae and Muribaculaceae, decrease the relative abundance of Prevotellaceae, and enhance the content of SCFAs(acetic acid, propionic acid, and butyric acid) in serum. This study suggested that the total ginsenosides from P. ginseng stems and leaves could improve lung edema, inflammatory response, and oxidative stress in ALI mice by regulating gut microbiota and SCFAs metabolism.

Development and clinical application of a new reduction device for the treatment of tibial plateau fracture under arthroscopic monitoring / 中国骨伤

OBJECTIVE@#To develop a reduction device for the arthroscopy-assisted treatment of tibial plateau fracture and explore its clinical efficacy.@*METHODS@#From May 2018 to September 2019, 21 patients with tibial plateau fracture were treated, including 17 males and 4 females. Their ages ranged from 18 to 55 years old with an average of (38.6±8.7) years old. There were 5 cases of Schatzker typeⅡand 16 cases of Schatzker type Ⅲ. The self-designed reductor combined with arthroscope was used for auxiliary reduction and fixation(minimally invasive percutaneous plate osteosynthesis). The efficacy was analyzed by observing the operation time, blood loss, fracture healing time and knee function(HSS and IKDC scoring criteria).@*RESULTS@#All the 21 patients were followed up for 8 to 24 with an average of(14.0±3.1) months. The operative time ranged from 70 to 95 min with an average of(81.7±7.6)min, incision length ranged from 4 to 7 cm with an average of(5.3±0.9) cm, intraoperative blood loss ranged from 20 to 50 ml with an average of(35.3±5.2) ml, postoperative weight-bearing time ranged from 30 to 50 d with an average of(35.1±9.2) d, fracture healing time ranged from 65 to 90 d with an average of(75.0±4.4) d, and complications were 0 cases, respectively. The fracture was well healed and no screw plate fracture was observed. The knee function scores of HSS and IKDC 18 months after operation were significantly higher than those before operation(P<0.05).@*CONCLUSION@#The custom-made reduction tool for the arthroscopic management of tibial plateau fracture is reasonable in design and simple in operation. The specific reduction tool could effectively reduce the fracture, and shorten the fixation time with minimally invasive procedure.

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice / 中国结合医学杂志

OBJECTIVE@#To investigate the pharmacodynamic material basis, mechanism of actions and targeted diseases of Salicornia europaea L. (SE) based on the network pharmacology method, and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.@*METHODS@#Retrieval tools including Chinese medicine (CM), PubMed, PharmMapper, MAS 3.0 and Cytoscape were used to search the components of SE, predict its targets and related therapeutic diseases, and construct the "Component-Target-Pathway" network of SE for central nervous system (CNS) diseases. Further, protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (n=10) including the normal group (nonstressed mice administered with distilled water), the CUMS group (CUMS mice administered with distilled water), the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg), SE high-, medium-, and low-dose groups (CUMS mice administered with SE 1.8, 1.35 and 0.9 g/kg, respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST), the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex, IL-2 and corticosterone (CORT) levels in blood, and nuclear factor E2 related factor 2 (Nrf2), kelch-like epichlorohydrin related protein 1 (Keap1), NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.@*RESULTS@#The "target-disease" network diagram predicted by network pharmacology, showed that the potential target of SE involves a variety of CNS diseases, among which depression accounts for the majority. The experimental results showed that SE (1.8, 1.35 g/kg) significantly decreased the immobility period, compared with the CUMS group in FST and TST in mice after 3-week treatment, while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group, the SE group (0.9 g/kg) showed significant differences (P<0.05) in DA levels in the hippocampus and cerebral cortex. In addition, compared with CUMS control group, SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (P<0.05), and serum IL-2 level with no statistical significance. Finally, Western blot results showed that compared with the model group, Nrf2, Keap1, NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all P<0.01).@*CONCLUSION@#The SE extract may have an antidepressant effect, which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

Effect of "Natural Polypill", Xuezhikang on Serum Cholesterol Metabolism Markers in Early Menopausal Women with Hypercholesterolemia / 中国结合医学杂志

OBJECTIVE@#To analyze the effect of Xuezhikang on the markers of the serum lipid levels of cholesterol synthesis and absorption in early menopausal women with hypercholesterolemia, and preliminarily explore its lipid-lowering mechanism.@*METHODS@#A total of 90 early menopausal women with hypercholesterolemia were enrolled from December, 2014 to May, 2016 from Beijing Anzhen Hospital, Capital Medical University, who were randomly allocated to receive Xuezhikang (1200 mg/d, orally) or atorvastatin (10 mg/d, orally) according to a random number table. Serum levels of some related biomarkers, including cholesterol synthesis markers (squalene, dihydrocholesterol, dehydrocholesterol, and lathosterol), and absorption markers (campesterol, stigmasterol, and sitosterol) as well as safety indices were obtained at baseline and after 8 weeks of the intervention.@*RESULTS@#Eight weeks after treatment, both Xuezhikang and atorvastatin significantly reduced the levels of total cholesterol, triglycerides, low density cholesterol compared to baseline (all P<0.01). Xuezhikang significantly reduced the levels of squalene, dehydrocholesterol and lathosterol compared to baseline (all P<0.01), but atorvastatin only significantly reduced the level of squalene (P<0.01), compared to baseline. All cholesterol absorption markers showed no significant differences before and after treatment (P>0.05), however, a more obvious downward trend was shown in the Xuezhikang group. In addition, all the safety indices showed no significant differences between the two groups. Although the creatinekinase level in the Xuezhikang group was significantly higher, it remained within the safe range.@*CONCLUSIONS@#Xuezhikang may have more comprehensive effects on the markers of cholesterol synthesis and metabolism in early menopausal women with hypercholesterolemia through ergosterol and flavonoids in its "natural polypill."

Study on preparation and formation mechanism of danazol-sodium caseinate composite nanoparticles / 中国药房

OBJECTIVE To prepar e and characterize danazol （DAZ）-sodium caseinate （SC）composite nanoparticles ，and to study the mechanism of preparing nanoparticles in “bottom-up”technology. METHODS SC was used as a stabilizer for regulating nanoparticles，so that DAZ-SC composite nanoparticles were prepared by anti-solvent precipitation method. The particle size ， Zeta-potential，micro-morphology，stability，encapsulation efficiency ，drug loading and in vitro dissolution rate were characterized. Fluorescence spectra ，IR spectra ，FBRM and other methods were used to analyze the interaction mechanism between DAZ and SC. RESULTS The particle size of DAZ-SC composite nanoparticles was （223.7±12.5）nm，and the polydispersity index was 0.274± 0.012. Zeta-potential was －（17.81±1.63）mV（n＝3）. The stability of nano-suspension was good ，the solid properties of DAZ were greatly improved ，and the dissolution rate was significantly increased. SC was statically quenched under the action of DAZ and the secondary structures of SC were changed. The crystallization process of DAZ was controlled under the action of SC ，and the interaction between DAZ and SC was mainly hydrogen bond and van der Waals force. CONCLUSIONS In this study ，DAZ-SC composite nanoparticles are successfully prepared. In the “bottom-up”technology，the interaction between SC and DAZ caused by hydrogen bond and van der Waals force inhibits the growth and agglomeration of drug crystals .

Establishment of a mouse model of vascular endothelial-mesenchymal transdifferentiation genetic tracing and its role in liver fibrosis studies / 临床肝胆病杂志

Objective To establish Cdh5-Cre ERT /Acta2-tdTomato-STOP floxed -eGFP knockin genetic tracing mice, and to investigate its application in studies on vascular endothelial cell transition in liver fibrosis. Methods Cdh5-Cre ERT mice were mated with Acta2-KI mice, and the Cdh5-Cre ERT /Acta2-KI genetic tracing mice were obtained and identified by PCR genotyping. Primary liver sinusoid endothelial cells (LSECs) were isolated and cultured, and a model of CCl 4 -induced liver fibrosis was established. LSECs and liver tissue were collected for immunofluorescent staining to observe the expression of the fluorescent proteins tdTomato and eGFP. Results After being induced by tamoxifen, LSECs and liver tissue of Cdh5-Cre ERT /Acta2-KI genetic tracing mice expressed eGFP under the conditions for epithelial-mesenchymal transdifferentiation established in vivo and in vitro, while the control group without induction expressed tdTomato alone. Conclusion The successfully established Cdh5-Cre ERT /Acta2-KI genetic tracing mice can realize the effective labeling of epithelial-mesenchymal transdifferentiation, which provides a genetic tracing basis for the diverse sources of mesenchymal myofibroblasts in liver fibrosis.

Cost-utility analysis of pertuzumab combined with trastuzumab and docetaxel in first-line treatment of HER 2- positive metastatic breast cancer / 中国药房

OBJECTIVE To study the metabolites of four diterpenoids of Euphorbia fischeriana in liver microsomes of rats and to investigate its metabolic regularity. METHODS In vitro incubation system of liver microsomes of rats was built. The jolkinolide A，jolkinolide B ，17-hydroxyl jolkinolide A and 17-hydroxyl jolkinolide B were added into incubation system of liver microsomes in rats activated by reduced nicotinamide adenine dinucleotide phosphate ，incubated at 37 ℃ for 30 min，and then terminated the reaction with acetonitrile. Taking the negative group （adding acetonitrile firstly and then starting incubation for 30 min）as the reference，the ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry was used ；Anaylyst®TF 1.7.1、PeakView® 2.2，MetabolitePilot 1.5 and MasterView 1.2 software were used to speculate and identify the fragmentation law of mass spectrometry and metabolites. RESULTS Four diterpenoids were easy to lose neutral fragments such as H 2O and CO in secondary mass spectrometry. Jolkinolide A and 17-hydroxyl jolkinolide A showed similar metabolism pathway ，including dihydroxylation，dehydrogenation，and monohydroxylation ；six and five metabolites were identified respectively. Jolkinolide B and 17-hydroxyl jolkinolide B showed similar metabolism pathway ，including monohydroxylation ，hydration and isomerization. Five metabolites were identified. CONCLUSIONS Both jolkinolide A and 17-hydroxyl jolkinolide A produce the metabolites of hydroxylation and dehydrogenation in liver microsomes of rats ；both jolkinolide B and 17-hydroxyl jolkinolide B produce the metabolites of hydroxylation ，hydration and isomerization in liver microsomes of rats. The metabolites of four diterpenoids are phase Ⅰ metabolites.

Diagnosis and treatment for emphysematous pyelonephritis: analysis of 14 cases from a single centre / 中华外科杂志

Objective: To examine the modalities of treatment and clinical outcomes of emphysematous pyelonephritis (EPN), in order to improve the survival rate of EPN patients. Methods: Totally 14 patients diagnosed as EPN between October 2011 and November 2020 at Department of Urology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine were included in this article. Data collection including patient demographics, clinical manifestations, management and clinical outcomes were conducted by retrospective charts review, after receiving the institutional review board's approval. There were 11 females and 3 males with a median age of 59 years (range: 52 to 73 years). The lesions were located on the left side in 10 patients and right side in 4 patients. All the 14 patients suffered from fever, and present with severe sepsis or septic shock. The median time from symptom onset to admission to hospital was 3 days(range: 2 to 5 days). All cases had diabetes mellitus. Escherichia coli was the most common organism been cultured (11 cases), while Klebsiella pneumonia was the second (3 cases). CT scan showed bubbly or located gas in the renal parenchyma in 5 cases and presence of steaky or mottled gas in the renal parenchyma in 9 cases. All patients had been admitted to ICU for anti-septic shock therapy. Three patients had undergone percutaneous catheter drainage along with broad-spectrum antibiotics therapy while 3 patients had immediate nephrectomy, the other 8 cases had a combination of an initial percutaneous catheter drainage and second stage nephrectomy. Results: In this case series, 3 patients were died from EPN while the other 11 were survived. The median ICU stay time was 6 days (range: 3 to 11 days). Of the 3 patients died from EPN, 2 had undergone percutaneous catheter drainage along and 1 had received immediate nephrectomy. Among the 11 patients who were survived, only 1 had received percutaneous catheter drainage while the other 10 received nephrectomy (8 patients had staged nephrectomy). Follow-up was performed 6 months after discharge. Of the 11 surviving patients, 2 were lost to follow-up, and the remaining 9 patients had an creatine level of (118.4±29.4) μmol/L (range: 89 to 176 μmol/L). Conclusions: For patients coupled with diabetes who were initially diagnosed as acute pyelonephritis, the possibility of EPN should be considered when the disease progressed rapidly especially septic shock occurred. On the basis of empirical broad-spectrum antibiotics therapy and standardized anti-septic shock treatment, a combination of an initial percutaneous catheter drainage and second stage nephrectomy could be efficacious.