Aberrantly high DEPDC1B expression leads to poor prognosis in patients with lower-grade gliomas.

OBJECTIVE: DEPDC1B, which encodes DEP domain-containing protein 1B, exerts pathogenic effects in diverse cancers, but no such effect has been reported in the case of lower-grade glioma (LGG). Therefore, we sought to investigate the relationship between DEPDC1B expression and the prognosis of patients with LGG and reveal the underlying molecular mechanism. MATERIALS AND METHODS: First, RT-qPCR and immunohistochemical staining were used to examine DEPDC1B mRNA and protein expression in LGG. Second, transcriptomic data were collected from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases to investigate the impact of DEPDC1B expression on LGG patients by using the Kaplan-Meier survival analysis, receiver operating characteristic analysis and Cox models. Third, the effects of DEPDC1B on LGG cell proliferation and migration were revealed using wound-healing and Cell Counting Kit-8 assays and Ki67 immunofluorescence staining. Fourth, the Tumor Immune Estimation Resource database was used to examine how DEPDC1B affects the LGG immune microenvironment, and gene set enrichment analysis was used to uncover the signaling pathways in which DEPDC1B is involved in LGG. RESULTS: DEPDC1B was significantly upregulated in both LGG cells and tissues, and high expression of DEPDC1B contributed to poor prognosis of LGG patients and represented an independent risk factor for LGG. Moreover, DEPDC1B knockdown reduced the proliferation and migration abilities of LGG cells. Lastly, DEPDC1B was found to be positively associated with multiple immune infiltrates and immune-checkpoint markers. CONCLUSIONS: Our findings indicate for the first time that DEPDC1B is a pathogenic gene in LGG. More importantly, we provide a new biomarker and immunotherapeutic target for improving the diagnosis and treatment of LGG patients.

Clinical correlation between volume of placental lakes and non-reassuring fetal status: a retrospective cohort study.

OBJECTIVE: This study evaluated the correlation between placental lakes and non-reassuring fetal status. SUBJECTS AND METHODS: We analyzed data from pregnant women who underwent fetal echocardiography at the Fujian Maternity and Child Health Hospital. Women with singleton pregnancies at a gestational age of 20-24 weeks were included. Sociodemographic and clinical data were collected. Pregnant women with (case group) and without (control group) placental lakes were screened, and their placental Doppler ultrasound data and pregnancy outcome were recorded. Univariate and multivariable analyses were done to evaluate the correlation between the volume of placental lakes and the non-reassuring fetal status. RESULTS: A total of 1,728 pregnant women (156 with placental lakes) were included in this study. There were no significant differences in age of delivery and BMI between the pregnant women with placental lakes and the control group. The non-reassuring fetal status rate in the case group was higher than that in the control population, without statistical significance (5.8% vs. 3.5%, p=0.226). Subgroup analysis showed that a higher volume of placental lakes was positively associated with non-reassuring fetal status risk, with an odds ratio (OR) (95% CI) of 1.90 (1.29-2.66) (p for trend < 0.001). This positive correlation persisted even after adjustment for confounding factors. CONCLUSIONS: Taken together, our analyses demonstrated a graded increase in the non-reassuring fetal status rate with increased volume of placental lakes. Thus, robust clinical monitoring of placental lakes would help in timely detection of non-reassuring fetal status.

Observation of a quantum phase transition in the quantum Rabi model with a single trapped ion.

Quantum phase transitions (QPTs) are usually associated with many-body systems in the thermodynamic limit when their ground states show abrupt changes at zero temperature with variation of a parameter in the Hamiltonian. Recently it has been realized that a QPT can also occur in a system composed of only a two-level atom and a single-mode bosonic field, described by the quantum Rabi model (QRM). Here we report an experimental demonstration of a QPT in the QRM using a 171Yb+ ion in a Paul trap. We measure the spin-up state population and the average phonon number of the ion as two order parameters and observe clear evidence of the phase transition via adiabatic tuning of the coupling between the ion and its spatial motion. An experimental probe of the phase transition in a fundamental quantum optics model without imposing the thermodynamic limit opens up a window for controlled study of QPTs and quantum critical phenomena.

Scoring system to predict the success rate of external cephalic versions and determine the timing of the procedure.

OBJECTIVE: We aimed to examine the prenatal clinical characteristics of women with single pregnancies undergoing external cephalic version (ECV) without anesthesia, develop a novel scoring system for predicting the ECV success rate, and demonstrate that this scoring system can be used to individualize the timing of ECV attempts. PATIENTS AND METHODS: We enrolled 270 women who underwent ECV without anesthesia at 37-40 weeks of gestation in the Fujian Maternity and Child Health Hospital from 2016 to 2019 and divided them into two ECV outcome groups (success vs. failure). We identified five clinical features (the fetal buttocks' station, the sum of the fundal height and station, the fetal head location, and whether the fetal head or buttocks could be grasped) as independent factors affecting the ECV success rate, and we scored them using a regression coefficient. RESULTS: Women with scores of 0-3 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 16.67%, 16.67%, and 38.88 weeks, respectively; those with scores of 4-6 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 65.75%, 58.90%, and 39.62 weeks, respectively; and those with scores of 7-9 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 93.71%,74.83%, and 40.00 weeks, respectively. CONCLUSIONS: The ECV success and vaginal delivery rates increased with the score, and the delivery gestational age showed an initial increase. To optimize the ECV procedure and reduce the hospital burden, this scoring system should be used routinely to predict the ECV success rate and determine the timing of ECV attempts.

[Clinical effectiveness of less invasive intramedullary nail fixation combined with titanium cable cerclage for subtrochanteric fractures].

OBJECTIVE: To evaluate the surgical technique and clinical effect of less invasive intrame-dullary nail fixation combined with titanium cable cerclage in the treatment of subtrochanteric fractures. METHODS: A retrospective study was performed in 46 cases of subtrochanteric fractures in Peking University People's Hospital from January 2015 to December 2017. Among them, there were 14 males and 32 females, with an average age of (77.83±10.66) years (44-92 years); 17 cases on the left side and 29 cases on the right side. The causes of injury included crash from a height, traffic accident and accidental fall. According to Seinsheimer classification, there were 26 cases of type Ⅱ, 11 cases of type Ⅲ, 9 cases of type Ⅳ, and these cases were all closed injury. After admission, these patients underwent continuous tibial tuberosity bone traction to maintain the length and force line of the lower extremity, so as to reduce the difficulty of intraoperative fracture reduction. Anticoagulant therapy was given before operation to reduce perioperative thrombotic complications. All the patients were treated with less invasive intramedullary nail fixation combined with titanium cable cerclage. Operation time, blood loss during surgery, time of fracture healing were recorded, Harris and Sanders scoring system were used to assess hip function after operation at each follow-up time point. RESULTS: All the included patients underwent surgery successfully. Average operative time and intraoperative blood loss of these patients were (131.09 ± 20.06) min and (191.96±111.03) mL, respectively. All the patients were followed up satisfactorily, with an average follow-up time of 28 months. The fractures received bone healing within 3-6 months, average hospital stay was (10.61±2.85) days. The Sanders score was excellent in 3 cases, good in 37 cases and common in 6 cases, with an excellent and good rate of 86.96%. The Harris score was excellent in 6 cases, good in 36 cases, with an excellent and good rate of 91.30%. There were no cases of wound infection, loss of reduction, nonunion of fracture or internal fixation failure. Hip pain symptoms were effectively relieved in most patients. CONCLUSION: Less invasive intramedullary nail fixation combined with titanium cable cerclage can obtain good alignment and stability of fracture ends, which is an effective method for the treatment of subtrochanteric fractures.

MicroRNA-130b inhibits cerebral ischemia/reperfusion induced cell apoptosis via regulation of IRF1.

OBJECTIVE: Cerebral ischemia/reperfusion (CIR) frequently causes serious disabilities and correlates with certain neurological processes. Some studies have shown that microRNAs (miRNAs) exert a neuroprotective effect by modulating the inflammatory process in CIR. However, the biofunction and the mechanism of miR-130b in CIR need to be fully elucidated. MATERIALS AND METHODS: An oxygen-glucose deprivation/reperfusion (OGD/R) model was constructed using SH-SY5Y cell line to analyze the function of miR-130b in CIR. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the expression levels of miR-130b and IRF1. Western blot was performed to detect the protein levels of IRF1, Bax, and Bcl-2. Cell viability was determined using MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays. Dual-Luciferase reporter assay was conducted to confirm the target gene of miR-130b. RESULTS: In this study, we found that miR-130b level was prominently decreased after treatment with OGD/R. Through gain and loss assays, we concluded that miR-130b restoration promoted cell proliferation and inhibited cell apoptosis in OGD/R-treated cells. Moreover, we also identified IRF1 as an important target of miR-130b. Additionally, IRF1 knockdown remarkably abrogated the protection mediated by miR-130b against the injuries in OGD/R-treated cells. CONCLUSIONS: Taken together, our results suggested that miR-130b facilitated cell viability and suppressed cell apoptosis of CIR via negatively regulating of IRF1.

[A mid-term clinical follow-up study on repair of the meniscus tears by a modified arthroscopic outside-in puncture suture technique].

OBJECTIVE: To investigate the clinical effect of a modified arthroscopic outside-in suture technique in the treatment of meniscus tear using a spinal needle. METHODS: From January 2015 to October 2017, 95 patients treated with this method were followed-up. Among these cases, there were 36 males and 59 females. The age of the patients ranged from 16 to 77 years, (46.79±18.07) years in average. Among them, there were 28 patieats aged 16-35, 53 patients aged 36-65, and 14 patients aged over 65 years old. 28 cases were diagnosed with medial meniscus tear, 43 cases with lateral meniscus tear and 24 cases with both medial and lateral meniscus tear. Causes of the injury included sports, sprain, etc. According to Barrett standard, the clinical healing of meniscus tear was judged. Lysholm score, knee range of motion, visual simulation score (VAS) and magnetic resonance imaging (MRI) were used to evaluate the postoperative knee function and recovery of the patients. RESULTS: The 95 patients were followed up for 22 to 36 months, with an average of (28.32±3.98) months. According to Barrett standard, 90 patients (94.7%) obtained meniscus clinical healing. Meniscal healing rates were 96.43%, 96.23% and 85.71% in the three age groups, respectively. The meniscal healing rate was lower in the elderly group, but there was no significant difference in statistical results (P=0.262). Five patients had deep tenderness in the joint space of the injured side, and the overstretch test was positive. The preoperative and postoperative VAS scores, Lysholm scores and knee motion were compared in each group, and the differences were statistically significant (P < 0.01). At the end of the last follow-up, there were no cases of knee joint effusion, swelling and interlocking, and the joint function was effectively improved in most patients. No surgical site infection, periarticular vascular/nerve injury or knotting reaction was found during the follow-up. CONCLUSION: This modified arthroscopic outside-in suture technique using a spinal needle has the characteristics of simple operation, small trauma and rapid recovery, and the mid-term follow-up results were satisfactory. Therefore, we consider this method to be a safe and efficient method for the treatment of meniscus anterior horn and body tear.

[A comparative study on the efficacy of transoral vestibular approach, via bilateral areola approach endoscopic and open thyroidectomy on stage T1b papillary thyroid carcinoma].

Objective: To compare the surgical efficacy and cosmetic satisfaction of the transoral endoscopic thyroidectomy by vestibular approach (TOETVA), endoscopic thyroidectomy via bilateral areola approach (BAA), and open thyroidectomy (OT) in the treatment of papillary thyroid carcinoma (PTC) in stage T1b. Methods: A total of 178 patients with PTC in stages pT1bN0M0 and pT1bN1aM0 treated from January 2017 to December 2018 were divided into TOETVA group (n=59), BAA group (n=43), and OT group (n=76). The baseline characteristics, relevant indexes of surgical efficacy and follow-up data were compared between the three groups, and also the surgical efficacy indexes were compared between unilateral lobectomy + central lymph node dissection (unilateral lobectomy subgroup) and bilateral lobectomy + central lymph nodes dissection (total resection subgroup). SPSS 19.0 statistical software was used for data analysis. Results: The mean ages of patients in TOETVA group and BAA group were significantly younger than those in OT group, and the proportion of women in TOETVA group and BAA group was significantly higher than that in OT group, all P<0.05. None of patients in TOETVA and BAA groups were converted to open surgery. Among TOETVA, BAA and OT groups, there were significant differences in the mean operation time [unilateral lobectomy subgroup: (198.0±45.2) min, (162.0±36.9) min and (79.4±28.6) min, P<0.05; total resection subgroup: (230.0±36.0) min, (219.8±68.1) min and (102.8±40.0) min, P<0.05], in total drainage volume [unilateral lobectomy subgroup: (195.0±55.6) ml, (178.1±50.4) ml and (127.0±30.1) ml, P<0.05; total resection subgroup: (221.1±46.7) ml, (245.3±71.2) ml and (137.7±41.6) ml, P<0.05], and the incidence of subcutaneous ecchymosis in TOETVA group or BAA group was higher than that in the OT group [5.1% (3/59), 11.6% (5/43) vs. 0, χ(2)=3.952 and 9.225 respectively, both P<0.05]. The mean level of C-reactive protein in TOETVA group was higher than that in OT group [(16.8±10.7) vs. (9.5±6.9), P<0.05]. Following-up in the third month after surgery between three groups in cosmetic satisfaction scores [(2.7±0.5) vs. (2.6±0.7) vs. (1.7±0.8)], scar self-consciousness scores (0[0,1] vs. 1[0,2] vs. 2[1,2]), and quality of life scores [(9.1±1.1) vs. (8.9±1.1) vs. (7.5±0.8)], cosmetic satisfaction and quality of life in TOETVA and BAA group were better than that in OT group, in terms of scar self-consciousness: TOETVA0.05). The median follow-up time of the three groups was 25 months (TOETVA group), 28 months (BAA group), and 32 months (OT group) respectively, without disease progression. Conclusion: TOETVA and BAA are optional surgical methods for PTC in stages pT1bN0M0 and pT1bN1aM0, with good safety and patient's cosmetic satisfaction.

[Evaluation of therapeutic efficacy of arthroplasty with Swanson prosthesis in the surgical treatment of 2-5 metatarsophalangeal joint diseases].

OBJECTIVE: Metatarsophalangeal joint is an important joint for daily weight-bearing walking. Osteoarthritis, osteochondrosis of the metatarsal head, rheumatoid arthritis can often cause the destruction of 2-5 metatarsophalangeal joint, leading to pain, limited joint movement and toe deformities, severely affecting the forefoot function. The purpose of this study is to report the results of middle-long term follow-up after performing Swanson double-stem silicon implant arthroplasty in patients with diseases of 2-5 metatarsophalangeal joint. METHODS: From January 2010 to October 2015, 21 patients with 2-5 metatarsophalangeal joint replacement were performed with Swanson double-stem silicone prosthesis. In the study, 16 cases were successfully followed up, 2 men and 14 women with an average age (66.7±5.5) years. There were 9 cases diagnosed with rheumatoid arthritis, 5 cases with severe osteoarthritis and 2 cases with osteochondrosis of the metatarsal head. The American Association of foot and ankle surgery Maryland foot scoring system and visual analogue score (VAS) were used to evaluate the walking function, metatarsophalangeal joint mobility and pain degree before and after surgery. RESULTS: The follow-up time ranged from 17 months to 5 years, with an average of 3.2 years. According to Maryland foot scoring system of the American Association of foot and ankle surgery, the preoperative score was (60.69±6.12) points and postoperative score was (88.13±5.84) points. Range of motion of metatarsophalangeal joint: preoperative: back extension 5.4°±3.1°, plantar flexion 4.4°±2.7°; postoperative: back extension 15.7°±4.5°, plantar flexion 12.2°±4.3°, the motion of 2-5 metatarsophalangeal joint after operation was significantly improved compared with that before operation (P < 0.01). The preoperative VAS was (6.8±0.9) points and the last follow-up was (2.3±0.8) points, the pain symptom of metatarsophalangeal joint was improved obviously after operation. The postoperative score was significantly higher than the preoperative score according to Maryland foot scoring system (P < 0.01), the excellent rate was 81.3%. CONCLUSIONS: With the advantages of alleviating pain, preserving the length and alignment of metatarsophalangeal joint, improving the function of walking, and correcting the deformity, Swanson double-stem silicon implant arthroplasty is a reproducible and safe option for the reconstruction of the 2-5 metatarsophalangeal joint. However, there is still some probability of adverse reactions and still room for improvement.

Knockdown of microRNA-103a-3p inhibits the malignancy of thyroid cancer cells through Hippo signaling pathway by upregulating LATS1.

MicroRNA (miR)-103a-3p has been shown to be involved in the development and progression of several types of cancer. However, the role of miR-103a-3p in thyroid cancer remains unclear. This study investigated the effects of miR-103a-3p on the biological characteristics of thyroid cancer cells and related mechanisms. In the present study, we found that the expression of miR-103a-3p was increased in thyroid cancer tissues compared to that in non-cancerous tissues. Additionally, the expression of miR-103a-3p in thyroid cancer cell lines (TPC-1, SW579, BHT101, K1) was markedly higher than that in the human thyroid cell line (Nthy-ori3-1). Silencing of miR-103a-3p obviously inhibited proliferation, migration, and invasion and promoted apoptosis of BHT101 cells. miR-103a-3p upregulation promoted the proliferation, migration, and invasion and inhibited apoptosis of K1 cells. Mechanistically, LATS1 was identified as a functional target of miR-103a-3p, and miR-103a-3p negatively regulated LATS1 expression. miR-103a-3p knockdown (or upregulation) partially reversed the effects of LATS1 knockdown (or overexpression) on proliferation, apoptosis, migration, and invasion of thyroid cancer cells. LATS1 knockdown inhibited the phosphorylation of YAP in BHT101 cells and promoted the nuclear translocation of YAP. Whereas, miR-103a-3p downregulation reversed the inhibitory effect of LATS1 knockdown on the Hippo signaling pathway. Moreover, overexpression of LATS1 induced YAP phosphorylation in K1 cells and inhibits nuclear translocation of YAP, and the upregulation of miR-103a-3p reversed this effect. The knockdown of miR-103a-3p inhibited tumor growth and progression in vivo. Taken together, knockdown of miR-103a-3p inhibits proliferation, migration, and invasion and promotes apoptosis of thyroid cancer cells through the Hippo signaling pathway by upregulating LATS1.

Long noncoding RNA SNHG8 promotes the proliferation of osteosarcoma cells by downregulating miR-542-3p.

Small nucleolar RNA host genes (SNHGs) as a subset of long noncoding RNAs (lncRNAs) have critical roles in the pathogenesis of multiple malignancies, however, the role and molecular mechanisms of lncRNA SNHG8 in osteosarcoma (OS) remain unclear. In the present study, the correlation of SNHG8 or miR-542-3p with clinicopathological elements and prognosis in OS patents was estimated by TCGA cohort. Cell viability and invasion were assessed by MTT and Transwell assays. The interplay between SNHG8 and miR-542-3p was affirmed by a luciferase report assay. The effects of SNHG8 on miR-542-3p expression were examined in MG-63 and SW-1353 cells by qRT-PCR analysis. The results showed that incremental expression of SNHG8 or reduced expression of miR-542-3p was related to poor survival and tumor recurrence in OS patients. Overexpressing SNHG8 accelerated the growth and invasion of MG-63 cells, but silencing SNHG8 harbored an opposite effect in SW-1353 cells. Additionally, SNHG8 could negatively regulate miR-542-3p expression and bind with miR-542-3p, which attenuated SNHG8 induced cell proliferation. Taken together, these findings indicate that lncRNA SNHG8 promotes the proliferation of OS cells by downregulating miR-542-3p.

[Application of multidisciplinary team (MDT) in the treatment of severe trauma].

OBJECTIVE: To explore the effect of multi-disciplinary team (MDT) in general hospitals on severe trauma patients. METHODS: This study reviewed the treatment of patients with severe trauma in trauma center of Peking University People's Hospital from March 2017 to April 2019. The baseline information: the patients' gender, age, injury mechanism, etc.; the start indicators: the Glasgow coma scale (GCS), trauma index (TI), injury severity score (ISS); the start related indicators: time for activation, time for MDT to arrive, time for CT scan, time for damage control surgery; patient treatment and prognosis: ICU (intensive care unit) length of stay, number of cured and discharged patients, number of dead cases, number of patients transferred to rehabilitation hospital, were all analyzed. It discussed the composition of MDT, the initiation scheme, the indicators of initiation of MDT for severe trauma, and analyzed the correlation between the application of MDT and the prognosis of patients. RESULTS: From March 2017 to April 2019, 112 trauma patients were treated by MDT in Peking University People's Hospital. There were 69 males and 43 females. The minimum age was 15 years, the maximum age was 89 years, most of them were 36-55 years old. The main injury mechanism was traffic accident injury. The GCS, TI, ISS were 13.0±2.9, 13.0±2.8, and 21.5±11.9, respectively. It took 3.7±0.8 minutes to start the call, 6.1±0.9 minutes for MDT personnel to arrive at the emergency rescue area, 23.8±3.0 minutes for fast CT and 92.6±15.4 minutes for injury control operation. All the hospitalized patients were treated effectively. ICU (Intensive care unit) hospitalization time was 12.6±6.7 days. 55 discharged patients were cured, 5 died (1 died of hemorrhagic shock, 4 died of severe brain injury) and 52 transferred to rehabilitation hospital. CONCLUSION: The treatment of severe trauma patients by MDT in trauma center of general hospitals can greatly improve the ability and level of treatment of severe trauma patients, make up for the lack of treatment of severe trauma especially multiple trauma patients in large general hospitals, and improve the treatment effect of severe trauma patients. It provides a reference model for large general hospitals to treat patients with severe trauma and multiple trauma and for the construction of trauma centers.

Circular RNA_LARP4 inhibits the progression of non-small-cell lung cancer by regulating the expression of SMAD7.

OBJECTIVE: Researchers have uncovered the importance of circular RNAs (circ) in malignant tumors. Circ LARP4 has been found to serve as a tumor suppressor gene in gastric cancer. However, the exact function of circ LARP4 in non-small-cell lung cancer (NSCLC) has not been fully elucidated. The aim of this study was to uncover the role of circ LARP4 in the tumorigenesis of NSCLC. PATIENTS AND METHODS: Expression level of circ LARP4 in NSCLC tissues was detected through Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Subsequently, the association between expression and patients' prognosis was analyzed. Circ LARP4 lentivirus was constructed and transfected into NSCLC cells. The effect of circ LARP4 on NSCLC cell migration and invasion was detected by function assays. Furthermore, Western blot was performed to analyze the expression of predicted protein of circ LARP4. RESULTS: Compared with adjacent tissues, circ LARP4 was lowly expressed in NSCLC tissues. Meanwhile, expression of circ LARP4 was associated with the prognosis of NSCLC patients. Downregulated circ LARP4 was found in NSCLC cell lines as well. The migration and invasion abilities of NSCLC cells were significantly inhibited via overexpression of circ LARP4. SMAD7, the predicted protein of circ LARP4, increased remarkably via overexpression of circ LARP4. CONCLUSIONS: Circ LARP4 could suppress the metastasis of NSCLC by up-regulating SMAD7.

[Study on the effect of diallyl sulfide on peripheral nerve injury in n-hexane intoxicated rats].

Objective: To investigate the antagonistic effect of diallyl sulfide (DAS) against peripheral nerve injury induced by n-hexane in rats. Methods: A total of 68 adult male Wistar rats were selected, among which 50 were randomly selected and divided into blank control group, DAS control group (100 mg/kg·bw) , n-hexane model group, low-dose DAS intervention group (50 mg/kg·bw) , and high-dose DAS intervention group (100 mg/kg·bw) . A rat model of peripheral nerve injury was established by n-hexane exposure, and the rats were treated with DAS at different doses. The changes in pyrrole adducts and behavior were observed, a metabolic analysis was performed for serum pyrrole adducts, and the intervention effect was evaluated. The remaining 18 rats were randomly assigned to the n-hexane model group, the low-dose DAS intervention group, and the high-dose DAS intervention group, with 6 rats in each group, as satellite groups used for the toxicokinetic analysis of serum pyrrole adducts. Results: Compared with the blank control group, the n-hexane model group and low-and high-dose DAS intervention groups had a significant reduction in body weight since week 2 (P<0.01) . Compared with the n-hexane model group at the end of the experiment at week 7, the high-dose DAS intervention group had a significantly higher body weight (P<0.05) , while there was no significant difference in body weight between the n-hexane model group and the low-dose DAS intervention group (P>0.05) . The n-hexane model group developed gait abnormality at week 2 of poisoning, while the low-and high-dose DAS intervention groups developed gait abnormality at weeks 3 and 5 of poisoning, respectively. At the end of the experiment, the n-hexane model group and the low-and high-dose DAS intervention groups had a significantly higher gait score than the blank control group (P<0.01) . At the end of the experiment, the n-hexane model group and the low-dose DAS intervention group had significantly shorter latency in rotarod test than the blank control group (P<0.01) , while there was no significant difference in latency between the DAS control group and the high-dose DAS intervention group (P>0.05) . Compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in latency in rotarod test (P<0.01) . Compared with blank control group, the n-hexane model group and the low-dose DAS intervention group had a significant increase in mean nerve conduction velocity (P<0.01) , while there was no significant difference between the blank control group and the DAS control group or high-dose DAS intervention group (P>0.05) , and compared with the n-hexane model group, the low-and high-dose DAS intervention groups had a significant increase in nerve conduction velocity (P<0.01) . Compared with the blank control group at the end of the experiment at week 7, the n-hexane model group and the low-and high-dose DAS intervention groups had significant increases in the concentration of pyrrole adducts in serum, urine, and hair (P<0.01) , while there was no significant difference between the blank control group and the DAS control group (P>0.05) , and the high-dose DAS intervention group had a significantly lower concentration of pyrrole adducts in serum, urine, and hair than the low-dose DAS intervention group (P<0.05) . Serum pyrrole adducts reached the peak level at 9-12 hours and then started to decrease. Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significantly shorter half-life period of serum pyrrole adducts (P<0.01) . Compared with the n-hexane model group, the high-and low-dose DAS intervention groups had a significant reduction in the area under the curve of serum pyrrole adducts (P<0.05) . Conclusion: DAS can antagonize peripheral nerve injury induced by n-hexane.

Patient-derived organoids of non-small cells lung cancer and their application for drug screening.

Patient-derived organoids (PDOs) are emerging as preclinical models with promising values in personalized cancer therapy. The purpose of this study was to establish a living biobank of PDOs from patients with non-small cell lung cancer (NSCLC) and to study the responses of PDOs to drugs. PDOs derived from NSCLC were cultured in vitro, and then treated with natural compounds including chelerythrine chloride, cantharidin, harmine, berberine and betaine with series of concentrations (0.5-30 µM) for drug screening. Phenotypic features and treatment responses of established PDOs were reported. Cell lines (H1299, H460 and H1650) were used for drug screening. We successfully established a living NSCLC organoids biobank of 10 patients, which showed similar pathological features with primary tumors. Nine of the 10 patients showed mutations in EGFR. Natural compounds chelerythrine chloride, cantharidin and harmine showed anticancer activity on PDOs and cell lines. There was no significant difference in the 95% confidence interval (CI) for the IC50 value of chelerythrine chloride between PDOs (1.56-2.88 µM) and cell lines (1.45-3.73 µM, p>0.05). PDOs were sensitive to berberine (95% CI, 0.092-1.55 µM), whereas cell lines showed a resistance (95% CI, 46.57-2275 µM, p<0.0001). PDOs had a higher IC50 value of cantharidin, and a lower IC50 value of harmine than cell lines (p<0.05, 7.50-10.45 µM and 4.27-6.50 µM in PDOs, 3.07-4.44 µM and 4.69-544.99 µM in cell lines, respectively). Both PDOs and cell lines were resistant to betaine. Chelerythrine chloride showed the highest inhibitory effect in both models. Our study established a living biobank of PDOs from NSCLC patients, which might be used for high-throughput drug screening and for promising personalized therapy design.

[Antioxidant mechanism of diallyl sulfide in inhibiting leucopenia in peripheral blood induced by benzene in rats].

Objective: To investigate the antioxidant mechanism of diallyl sulfide (DAS) in antagonizing the reduction in peripheral blood white blood cells (WBC) induced by benzene in rats. Methods: A total of 60 specific pathogen-free adult male Sprague-Dawley rats, with a body weight of 180-220 g, were selected, and after 5 days of adaptive feeding, they were randomly divided into blank control group, DAS control group, benzene model group, benzene+low-dose DAS group, benzene+middle-dose DAS group, and benzene+high-dose DAS group, with 10 rats in each group. The rats in the benzene+low-dose DAS group, the benzene+middle-dose DAS group, the benzene+high-dose DAS group, and the DAS control group were given DAS by gavage at a dose of 40, 80, 160, and 160 mg/kg·bw, respectively, and those in the blank control group and the benzene model group were given an equal volume of corn oil; 2 hours later, the rats in the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group were given a mixture of benzene (1.3 g/kg·bw) and corn oil (with a volume fraction of 50%), and those in the blank control group and the DAS control group were given an equal volume of corn oil. The above treatment was given once a day for 4 consecutive weeks. At 1 day before treatment, anticoagulated blood was collected from the jugular vein for peripheral blood cell counting. After anesthesia with intraperitoneally injected pentobarbital (50 mg/kg·bw), blood samples were collected from the abdominal aorta, serum was isolated, and the thymus, the spleen, and the femur were freed at a low temperature to measure oxidative and antioxidant indices. The femur at one side was freed for WBC counting in bone marrow. Results: Compared with the blank control group, the benzene model group had significant reductions in the volume, weight, and organ coefficient of the spleen and the thymus (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had significant increases in the volume of the spleen and the thymus and the weight and organ coefficient of the spleen (P<0.05), and the benzene+middle-dose DAS group and the benzene+high-dose DAS group had significant increases in the weight and organ coefficient of the thymus (P<0.05). Compared with the blank control group, the benzene model group had a significant reduction in WBC count in peripheral blood and bone marrow (P<0.05), and compared with the benzene model group, the benzene+middle-dose DAS group and the benzene+high-dose DAS group had a significant increase in WBC count in peripheral blood and bone marrow (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the serum level of malondialdehyde (MDA) (P<0.05) and significant reductions in total superoxide dismutase (T-SOD) activity, reduced glutathione (GSH) level, GSH/oxidized glutathione (GSSG) ratio, total antioxidant capacity (T-AOC) (P<0.05) ; compared with the benzene model group, the benzene+high-dose DAS group had a significant reduction in the serum level of MDA and significant increases in T-SOD activity, GSH level, GSH/GSSG ratio, and T-AOC (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA (P<0.05) and significant reductions in GSH level, GSH/GSSG ratio, and T-AOC (P<0.05) in the spleen; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in MDA level (P<0.05) and significant increases in GSH level and T-AOC (P<0.05), and the benzene+high-dose DAS group had significant increases in T-SOD activity and GSH/GSSG ratio (P<0.05). Compared with the blank control group, the benzene model group had a significant increase in the level of MDA in bone marrow cells (BMCs) and peripheral blood mononucleated cells (PBMCs) (P<0.05) and a significant reduction in T-AOC in PBMCs (P<0.05) ; compared with the benzene model group, the benzene+low-dose DAS group, the benzene+middle-dose DAS group, and the benzene+high-dose DAS group had a significant reduction in the level of MDA in BMCs and PBMCs (P<0.05), and the benzene+high-dose DAS group had significant increases in GSH level and GSH/GSSG ratio (P<0.05) . Conclusion: DAS can antagonize the benzene-induced reduction in peripheral blood WBC, possibly by exerting an anti-oxidative stress effect.

[Lag effect and influencing factors of temperature on other infectious diarrhea in Zhejiang province].

Objective: To study the lag effect of temperature and the source of heterogeneity on other infectious diarrhea (OID) in Zhejiang province, so as to identify related vulnerable populations at risk. Methods: Data on OID and meteorology in Zhejiang province from 2014 to 2016 were collected. A two-stage model was conducted, including: 1) using the distributed lag non-linear model to estimate the city-specific lag effect of temperature on OID, 2) applying the multivariate Meta- analysis to pool the estimated city-specific effect, 3) using the multivariate Meta-regression to explore the sources of heterogeneity. Results: There were 301 593 cases of OID in Zhejiang province during the study period. At the provincial level, temperature that corresponding to the lowest risk of OID was 16.7 ℃, and the temperature corresponding to the highest risk was 6.2℃ (RR=2.298, 95%CI: 1.527- 3.459). 16.7 ℃ was recognized as the reference temperature. P(5) and P(95) of the average daily temperature represented low and high temperature respectively. When the temperature was cold, the risk was delayed by 2 days, with the highest risk found on the 5(th) day (RR=1.057, 95%CI: 1.030-1.084) before decreasing to the 23(rd) day. When the temperature got hot, the risk of OID occurred on the first day (RR=1.081, 95%CI: 1.045-1.118) and gradually decreasing to the 8(th) day. Differences on heterogeneous sources related to the risks of OID in different regions, presented on urban latitude and the rate of ageing in the population. Conclusions: Both high or low temperature could increase the risk of OID, with a lag effect noticed. Prevention program on OID should be focusing on populations living in the high latitude and the elderly population at the low temperature areas.