[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

[Clinical analysis of 12 cases of ovarian yolk sac tumor].

Objective: To investigate the diagnosis, treatment and prognosis of ovarian yolk sac tumor (OYST). Methods: The clinicopathological data and follow-up data of 12 patients with OYST admitted to the Affiliated Hospital of Qingdao University from January 2013 to December 2020 were retrospectively analyzed, and the diagnosis, treatment and prognosis of OYST patients were summarized. Results: (1) The age of 12 patients with OYST ranged from 11 to 37 years, with a median age of 20 years. At the first visit, all 12 patients had pelvic masses. Reasons for seeing a doctor: 6 cases of abdominal distension and abdominal pain, 4 cases of mass in the lower abdomen, 1 case of vaginal bleeding, and 1 case of appendicitis. International Federation of Obstetrics and Gynecology (FIGO) 2014 staging: 4 cases in stage Ⅰa, 2 cases in stage Ⅰc, 1 case in stage Ⅱc, 4 cases in stage Ⅲc, and 1 case in stage Ⅳb. (2) All 12 patients were examined by color Doppler ultrasound before operation, among which 10 cases showed unilateral adnexal masses and 2 cases bilateral adnexal masses. The median maximum diameter of tumor was 16.5 cm (range: 6.0-28.0 cm). The preoperative levels of alpha fetoprotein (AFP) in 12 patients (all >1 210 µg/L) were significantly higher than normal (<25 µg/L). Among the 11 patients with cancer antigen 125 (CA125) detection results, 9 patients showed elevated serum CA125 levels. (3) Among the 12 patients, 8 young infertile patients who needed to preserve their reproductive function underwent appendectomy, 3 infertile patients underwent staged surgery for ovarian malignant germ cell tumor, and only one bilateral lesion and infertile patient underwent unsatisfactory staged surgery for ovarian malignant germ cell tumor. Of the 12 patients, 11 patients were given combined chemotherapy regimen of bleomycin, cisplatin, and etoposide (BEP) after operation. One patient without chemotherapy developed metastasis 3 months after operation, and was given BEP chemotherapy, and her condition was controlled. (4) The deadline for follow-up was December 31st, 2022, and the median follow-up time was 60 months (range: 25-115 months). All the 12 patients survived without tumor during the follow-up period, and the median disease-free survival time was 84.5 months (range: 25-115 months). Conclusions: OYST mostly occurs in children and young women. Color Doppler ultrasound examination and serum AFP and CA125 detection have diagnostic value for OYST. Surgical treatment after diagnosis of OYST includes surgery to preserve reproductive function and timely and standardized chemotherapy after operation. The prognosis of patients is good regardless of stage.

[Magnetic resonance imaging features and classification of intraductal papillary neoplasm of the bile duct].

Objective: To explore the magnetic resonance imaging (MRI) features and classification of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Data from 90 patients with intraductal papillary neoplasm of the bile duct confirmed pathologically between June 2010 and January 2023 were retrospectively analyzed. The image analysis included the shape and location of the tumor, whether bile ducts had dilatation and the degree of dilation, whether there was a history of liver disease, whether there was a history of schistosomiasis, whether there was cancerous transformation, whether there were concurrent bile duct stones, whether there was hepatic lobe atrophy, whether there was hilar or abdominal lymph node enlargement, whether there was invasion of the bile duct wall, whether there was invasion of surrounding blood vessels, whether the tumor appears on T1-and T2 weighted imaging (T(1)WI and T(2)WI), whether the diffusion was limited, whether there was concurrent bleeding, enhancement rate, and whether there was abdominal fluid accumulation. Intraductal papillary neoplasms of the bile duct were divided into four types according to the morphological classification standards: type I (local bile duct dilation), type II (cystic), type III (free tumor), and type IV (dilated bile duct). The differences in the clinical and MRI features of the four groups of lesions were analyzed. Statistical analysis was performed with a t-test, an analysis of variance, and an χ(2)-test according to the different data. Results: Among the 90 cases with hepatic IPNB, there were 31 cases of type I, 15 cases of type II, 16 cases of type III, and 28 cases of type IV, 41 cases of liver left lobe, 11 cases of right and left lobe liver span, 7 cases of liver right lobes, 2 cases of liver caudate lobe, and 13 cases of hepatic hilar. There were statistically significant differences between the four groups (P < 0.05) in terms of age, clinical symptoms, direct bilirubin, γ-glutamyltransferase, whether they were cancerous, whether they were combined with bile duct stones, whether the liver lobes were atrophying, whether there was limited diffusion, intrahepatic bile duct diameter, and common bile duct diameter. However, there were no statistically significant differences among the four groups in gender, location, carbohydrate antigen 19-9, history of liver disease, history of schistosomiasis, carcinoembryonic antigen, alanine aminotransferase, aspartate aminotransferase, total bilirubin, whether hemorrhage was associated, lesion enhancement rate, whether the hilar/retroperitoneal lymph node was enlarged, whether the bile duct wall was invaded, whether blood vessels were invaded, and whether abdominal fluid was accumulated (P > 0.05). Conclusion: MRI manifestations have certain features for different types of intraductal papillary neoplasm of the bile duct tumors; hence, MRI aids in the diagnosis and differential diagnosis of this disease.

[Effects of remimazolam versus propofol on postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy].

Objective: To investigate the effects of remimazolam versus propofol on postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Methods: A total of 108 elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy under general anesthesia in the Affiliated Cancer Hospital of Zhengzhou University from May to October 2022 were prospectively included. The participants were divided into two groups by the random number table method: remimazolam group (R group, n=54) and propofol group (P group, n=54). There were 54 cases in the R group, with 35males and 19 females, and aged (65.4±3.1) years. Meanwhile, there were 54 cases in the P group, with 33males and 21 females, and aged (64.5±3.0) years. Anesthesia was induced as follows: remimazolam 0.2-0.3 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in R group, while propofol 1-2 mg/kg and remifentanil 0.5-1.0 µg/kg were intravenously injected in P group. Subsequently, anesthesia was maintained as follows: remimazolam 0.4-1.0 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group R, while propofol 4-10 mg·kg-1·h-1 and remifentanil 0.05-0.2 µg·kg-1·min-1 were intravenously infused in group P. Bispectral index (BIS) was maintained at 45-60 during operation. The main outcome measures were the 15-item quality of recovery (QoR-15) scores 1 day before surgery, 1 day and 3 days after surgery. Secondary outcome measures included mean arterial pressure (MAP), heart rate and pulse oxygen saturation (SpO2) recorded 5 min before anesthesia induction (T0), 1 min after induction (T1), 1 min after endotracheal intubation (T2), immediately after skin incision (T3) and tracheal extubation (T4). The incidence of bradycardia and hypotension and the frequency of application of vasoactive drugs during anesthesia were recorded. Restlessness score (RS) and Ramsay sedation scale during the awakening period were recorded. Emergence time, tracheal extubation time, duration of postanesthesia care unit (PACU) stay and postoperative length of hospital stay were recorded. The incidence of postoperative pulmonary infection and other complications were also recorded. Results: The QoR-15 scale scores [M (Q1, Q3)] of R group 1 day and 3 days after surgery were 114.0 (109.0, 118.3) and 131.0 (127.8, 133.0), which were higher than those of P group [106.0 (101.0, 112.0) and 127.0 (125.0, 129.3)] (both P<0.001). The incidence of bradycardia, hypotension and the frequency of application of vasoactive drugs of R group during anesthesia were 5.6% (3/54), 35.2% (19/54) and 27.8% (15/54), which were lower than those in P group [33.3% (18/54), 63.0% (34/54) and 55.6% (30/54), respectively] (all P<0.05). RS score during the awakening period in R group was 0.9±0.5, which was lower than that of P group (1.1±0.6) (P=0.046). Emergence time, tracheal extubation time and postoperative length of hospital stay of R group were (15.4±4.9) min, (16.6±4.7) min and (11.6±1.4) d, which were shorter than those of P group [(26.2±6.4) min, (27.8±5.8) min and (12.6±1.3) d] (all P<0.05). There were no statistically significant differences in Ramsay scores during the awakening period, duration of PACU stay and the incidence of postoperative complications (all P>0.05). Conclusions: Both remimazolam and propofol can achieve satisfactory postoperative recovery quality in elderly patients undergoing thoracoscopic laparoscopic radical esophagectomy. Remimazolam has more stable hemodynamics and lower incidence of adverse reactions.

[The efficacy and safety of domestic magnetic resonance-guided laser interstitial thermotherapy in the treatment of recurrent high-grade glioma].

Sixteen patients with recurrent high-grade glioma who were treated by domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the Neurosurgery Department of Xuanwu Hospital of Capital Medical University from 1st January 2021 to 31st December 2021 were prospectively included, with 11 males and 5 females, and aged 27-74 (50±16) years. The duration of surgery, the rate of ablation after surgery, and perioperative complications were assessed. The patients were followed up every 3 months to assess survival and progression. A total of 5 WHO grade Ⅲ patients and 11 WHO grade Ⅳ patients were included. The operation time was 144 (109, 176) min, 28 targeted lesions were detected, and the ablation rate [M (Q1, Q3)] was 91.0% (87.4%, 93.3%). After surgery, 2 patients (2/16) had decreased limb muscle strength, and no perioperative death or other serious complications occurred. The median time to a complete response was 12 (5, 14) months in WHO Grade Ⅲ patients, and one died 12 months after surgery, while the median time to a complete response was 3 (1, 8) months in 11 WHO Grade Ⅳ patients, with a total of 8 deaths at the last follow-up. Therefore, domestic MRgLITT has certain efficacy and safety in the treatment of recurrent high-grade glioma, providing a new option for patients with recurrent glioma.

[Analysis of strong invasive clinical features and poor prognosis in macrotrabecular-massive hepatocellular carcinoma].

Objective: To analyze the correlation between the histological classification of hepatocellular carcinoma (HCC), especially macrotrabecular-massive (MTM), tumor invasiveness, and prognosis. Methods: The clinical and follow-up data of 246 consecutive HCC cases who met the inclusion criteria from 2015 to 2018 were retrospectively analyzed. They were divided into trabecular/pseudoglandular, trabecular/patchy, and MTM types according to the histological classification. The relationship between each type and related clinicopathological features was analyzed. The Kaplan-Meier method was used to plot tumor-free survival (DFS) and overall survival (OS) curves. Log rank tests, COX univariate, and multivariate regression analyses were conducted to analyze the relationship between clinical features, including histological classification, DFS, and OS. Results: Trabecular/pseudoglandular, trabecular/nodular, and MTM type proportions were 44.7% (110 cases), 32.9% (81 cases), and 22.4% (55 cases), respectively. The results of the clinicopathological features showed that MTM-type HCC was significantly more invasive than the other two types, with alpha-fetoprotein (AFP) ≥400 ng/ml, tumor diameter≥8 cm, no tumor capsule, poor differentiation, and MVI positivity proportions, and the differences were statistically significant (P < 0.05).The proportion of MTM-type HCC patients with American Joint Committee on Cancer TNM Stage III to IV and Chinese Liver Cancer Staging (CNLC) II to II was significantly higher than that of the first two types, and the differences were statistically significant (P < 0.05). In addition, the proportion of MTM subtypes undergoing transcatheter arterial chemoembolization was also raised (P < 0.05). The DFS and OS were significantly lower for MTM-type HCC compared to trabecular/pseudoductal-type HCC at 1-, 3-, and 5-years, and the differences were statistically significant (P < 0.05). Univariate analysis indicated that strongly invasive clinical pathological features such as alpha fetoprotein (AFP) ≥400 ng/ml, tumor diameter ≥ 8 cm, no tumor capsule, poor differentiation, positive microvascular invasion, tumor stage, and MTM staging were all risk factors affecting DFS and OS (P < 0.05). Multivariate COX analysis showed that MTM histological staging, AFP ≥ 400 ng/ml, tumor non-encapsulation, satellite nodules, CNLC stages II~III, and TNM stages III~IV were independent risk factors for DFS (P < 0.05), while AFP ≥ 400 ng/ml, tumor non-encapsulation, and CNLC stage II~III were independent risk factors for OS ( P < 0.05). Conclusion: Histological classification is highly correlated with tumor invasiveness and HCC prognosis. Trabecular/pseudoglandular types have lower malignancy and a better prognosis, while MTM types exhibit strong invasive features and a poor prognosis.

[Safety and efficacy of dual guiding catheter kissing technique in the treatment of stent partially dislodgement in coronary artery].

Objective: To investigate the safety and efficacy of dual guiding catheter kissing technique (DCK) in the treatment of stent partly dislodgement in coronary artery. Methods: The study retrospectively involved 6 hospitalized patients with coronary artery stent partly dislodgement during PCI at The First Affiliated Hospital of Zhengzhou University from February 2016 to June 2019, DCK was used in these patients. We observe the success rate of stent retrieval, success rate of PCI, incidence of complications and major adverse cardiovascular events in 1 year follow up. Results: 6 patients were involved, of which 3 are male, ages range 49 to 68 years old, 4 patients are diagnosed with unstable angina, the other two are stable angina. All the partially disloged stents in the 6 patients were successfully removed from coronary artery. Except for 1 patient who refused coronary artery stenting again, the other 5 patients were successfully implanted coronary artery stenting. No serious complications occurred, no patients died and no major adverse cardiovascular events happened during 1 year follow up. Conclusions: DCK is safe and effective to remove partially dislodged stent in coronary artery.

Photoluminescence and magnetism integrated multifunctional black phosphorus probes through controllable PO bond orbital hybridization.

Biological probes with integrated photoluminescence and magnetism characteristics play a critical role in modern clinical diagnosis and surgical protocols combining fluorescence optical imaging (FOI) with magnetic resonance imaging (MRI) technology. However, traditional magnetic semiconductors can easily generate a spin splitting at the Fermi level and half-metallic electronic occupation, which will sharply reduce the radiation recombination efficiency of photogenerated carriers. To overcome this intrinsic contradiction, we propose a controllable oxidation strategy to introduce some particular PO bonds into black phosphorus nanosheets, in which the p orbital hybridization between P and O atoms not only provides some carrier recombination centers but also leads to a room-temperature spin polarization. As a result, the coexistence of photoluminescence and magnetism is realized in multifunctional black phosphorus probes with excellent biocompatibility. This work provides a new insight into integrating photoluminescence and magnetism together by intriguing atomic orbital hybridization.

A novel bacteriocin BM1029: physicochemical characterization, antibacterial modes and application.

AIM: Bacteriocins with antimicrobial activity are considered as potential natural bio-preservatives to control the growth of food spoilage bacteria. The aim of this work was to characterize a novel bacteriocin BM1029 discovered from Lactobacillus crustorum MN047 and evaluate its antibacterial mechanism. METHODS AND RESULTS: Bacteriocin BM1029 was purified by cation-exchange chromatography and reversed-phase chromatography. Antibacterial activity assay showed that BM1029 is antagonistic against both Gram-positive and Gram-negative bacteria. Furthermore, it was found that BM1029 showed low haemolysis with high stability to the pretreatment with different temperatures, pH and surfactants. Moreover electron microscopy and flow cytometry suggested that BM1029 inhibit indicator strains by damaging the cell envelope integrity. Cell cycle assay suggested that BM1029 arrested cell cycle in R-phase. CONCLUSION: The novel bacteriocin BM1029 showed high bactericidal activity against Escherichia coli and Staphylococcus aureus through a cell envelope-associated mechanism. SIGNIFICANCE AND IMPACT OF THE STUDY: Application of BM1029 inhibited the growth of indicator strains on beef meat storage at 4°C suggesting that this bacteriocin is promising to be used as a novel preservative in food processing and preservation.

[????The diagnostic performance of the combination of ASL and TOF MRA for the cerebral arteriovenous shunt].

Objective: To evaluate the diagnostic performance of the combination of arterial spin labeling (ASL) and time of flight MR angiography (TOF MRA) for intracranial arteriovenous shunt (AVS) detection. Methods: A total of 39 patients with known or suspected with cerebrovascular malformations underwent digital subtraction angiography (DSA) and ASL/TOF MRA imaging in Department of neurosurgery and radiology and nuclear medicine, Xuanwu Hospital from May 1, 2020 to October 31, 2020 were retrospectively analyzed. Patients were divided into either acute cerebral hemorrhage group (n=13) or non-acute cerebral hemorrhage group (n=26) based on the signs of bleeding on imaging findings. According to history of treatment, those patients were divided into treated (n=11) and untreated (n=28) subgroups. The determination of the presence of AVS on images was judged by two radiologists in a blinded and randomized order fashion. The diagnostic performance of ASL or TOF MRA for AVS were evaluated in overall, acute cerebral hemorrhage subgroup and treated subgroup by using the area under receiver operating curve (AUC) with DSA as the reference standard, respectively. The κ coefficients were calculated to determine the interobserver agreement. Results: Among 39 patients, 29 patients were confirmed with AVS by DSA while 10 patients with no AVS. Interobserver agreement was good-excellent (κ=0.83-1.00). In patients with AVM, the detection rates for AVS of ASL or TOF MRA were 93.1% and 86.2% respectively, while the detection rates of the combination of ASL and TOF MRA were 100%. The AUC of ASL, TOF MRA and their combination for diagnosis of AVS in overall were 0.966 (95%CI: 0.909-1.00), 0.914 (95%CI: 0.825-1.00) and 0.983 (95%CI:0.943-1.00), respectively. The AUC of ASL, TOF MRA and their combination for AVS in acute cerebral hemorrhage subgroup were 1(95%CI:1.00-1.00), 0.833(95%CI:0.611-1.00), 1(95%CI:1.00-1.00), respectively. Conclusion: Combination of ASL and TOF MRA can be a non-invasive thchnique for the detection of AVS.

[Safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy in the treatment of drug-resistant epilepsy].

Objective: To investigate the safety and short-term efficacy of domestic magnetic resonance-guided laser interstitial thermotherapy (MRgLITT) in the treatment of drug-resistant epilepsy. Methods: Patients with drug-resistant epilepsy treated with a domestic MRgLITT system in the Department of Neurosurgery, Xuanwu Hospital, Capital Medical University from October 2020 to April 2021 were prospectively enrolled. The damage volume ratio was assessed immediately after surgery, and perioperative complications were recorded and followed up. The clinical safety and short-term efficacy were evaluated using the Engel classification. Results: A total of 22 patients were included, including 12 males and 10 females, aged from 3 to 45 years old [(24±13) years]. There were 5 cases of medial temporal lobe epilepsy (MTLE), 3 cases of hypothalamic hamartoma (HH), 7 cases of focal cortical dysplasia (FCD), and 7 cases of other types, respectively. The mean operation time and blood loss was (173±49) min and (3.7±1.6) ml. The postoperative length of hospital stay was (5.5±1.8) days, and the average damage volume ratio was 92.6%. Among them, only 2 patients (FCD of the parietal lobe) showed transient contralateral limb weakness, without any serious complications such as symptomatic intracranial hemorrhage and cerebral infarction. The follow-up time was 14 to 168 days. There were 13 Engel class Ⅰ cases (59.1%), 2 Engel class Ⅱ cases (9.1%), 2 Engel class Ⅲ cases (9.1%) and 5 Engel class Ⅳ cases (22.7%), respectively. Short-term incident-free rates were MTLE 5/5and FCD4/7, respectively. Conclusion: Domestic MRgLITT system is stable, reliable and safe in the treatment of drug-refractory epilepsy, and has better short-term efficacy in MTLE and FCD patients.

[Observation of efficacy and safety of stereotactic-EEG-guided three-dimensional radiofrequency thermocoagulation for the treatment of drug-resistant insular epilepsy].

Objective: To investigate the safety and efficacy of stereotactic-EEG (SEEG)-guided radiofrequency thermocoagulation (RF-TC) with three-dimensional lesioning in the treatment of drug-resistant insular epilepsy. Methods: Seven patients with drug-resistant insular epilepsy who underwent SEEG-guided RF-TC with three-dimensional ablation at the Department of Neurosurgery of Xuanwu Hospital, Capital Medical University from February 2017 to June 2019 were retrospectively enrolled. Presurgical evaluation including semiology, EEG and imaging results suggested that the epileptogenic zone was located in the insular lobe. All patients underwent SEEG recording and three-dimensional RF-TC. Postoperative follow-up was conducted by outpatient visits or telephone, the clinical efficacy was evaluated based on Engel classification and the relevant complications were documented. Results: Seven patients were followed up at 18 months after surgery. Among them, 4 were seizure free (Engel ⅠA), 2 had nondisabling simple partial seizures (Engel ⅠB) and 1 achieved 75% decrease (Engel ⅢA) in seizure frequency. Postoperative complications occurred in 3 patients which included decreased sensation in the right lower extremity, decreased strength in the right upper extremity, glossolalia, decline in memory and comprehension. No permanent neurological dysfunction was detected. Conclusion: SEEG-guided RF-TC with three-dimensional lesioning is minimally invasive, safe and effective in the treatment of drug-resistant insular epilepsy and can serve as a complementary method for resection surgery.

[Evaluations of total hilar en bloc resection and reconstruction in comparison with portal vein resection and reconstruction in treatment of perihilar cholangiocarcinoma].

Objective: To evaluate the feasibility and efficacy of total hilar en bloc resection and reconstruction(THERR) and portal vein resection and reconstruction(PVRR) in treatment of perihilar cholangiocarcinoma(PHC). Methods: Data of a total of 101 consecutive patients with PHC who underwent bile duct resection with various types of hepatectomies from June 2013 to December 2019 at Department of Hepatopancreatobiliary,Lihuili Hospital were retrospectively analyzed. Patients who underwent PHC resection combined with THERR or PVRR were identified and grouped accordingly. Fourteen patients(6 males, 8 females, aged (64.3±9.7)years old) underwent hepatectomy combined with THERR, 19 patients(11 males, 8 females, aged (63.8±8.6)years old) underwent hepatectomy combined with PVRR. Indications and surgical procedures of THERR and PVRR were reported. The clinicopathological characteristics and operation data, as well as the short and long-term outcomes of patients of the two groups were compared by Student's t-test and the χ2 test or Fisher exact test, respectively. The actual survivals rates were calculated by using the Kaplan-Meier method, and compared using the Log-rank test. Results: There were no statistically significant differences between the two groups in respect to age,sex and whether they had preoperative biliary drainage or not. The types of combined hepatectomy carried out predominately between the two groups were statistically different with the left side being predominant in the THERR group(10/14,P=0.010) and right side in PVRR group(12/19,P=0.001). There were no significant differences between the two groups in respect to whether they received preoperative portal vein embolization,intraoperative blood loss,curative degree,number of lymph node dissections, and whether there was lymphatic metastasis or not. However, both the times of operation and continuous Pringle maneuver were statistically longer in the THERR group((586±158)minutes and (32.5±7.3)minutes)than those in the PVRR group((453±88)minutes and (12.4±3.8)minutes),respectively(t=3.087,P=0.004;t=10.325,P<0.01). One patient in the THERR group died of liver failure 9 days postoperative, the cumulative 1-, 3- and 5-year survival rates were 84.9%, 57.1% and 37.0% for the THERR group and 81.9%, 37.8% and 30.2% for the PVRR group, respectively. There was no statistically significant differences between the two groups(χ²=0.150,P=0.698). Conclusions: Compared to the role of PVRR in the treatment of PHC, THERR is a novel and technically demanding procedure that is feasible in selected patients for the treatment of advanced PHC with invasion of both the hepatic artery and portal vein. However,due to the small size of this primary study,the value of THERR needs further evaluation.

[Visual quality after implantation of a rotational asymmetric refractive intraocular lens in patients with high myopia and cataract].

Objective: To evaluate the visual quality after phacoemulsification and implantation of a rotational asymmetric refractive intraocular lens in patients with high myopia and cataract. Methods: A retrospective cohort study. Sixty-two patients (92 eyes) of the First Affiliated Hospital of Zhengzhou University from June 2017 to December 2019 were evaluated after phacoemulsification and implantation of a rotational asymmetric refractive intraocular lens (LS-313 MF30). According to the axial length, the participants were allocated to either a control group or a high myopia group. Among the 33 patients (46 eyes) in the control group, the axial length was shorter than 26 mm; among the 29 patients (46 eyes) in the high myopia group, the axial length was more than 26 mm. The high myopia group was further divided into two subgroups. The super high myopia subgroup included 12 patients (18 eyes), and the axial length was ≥30 mm; the high myopia subgroup consisted of 17 patients (28 eyes), and the axial length was<30 mm and ≥26 mm. Uncorrected distance visual acuity, uncorrected intermediate visual acuity and uncorrected near visual acuity were recorded after surgery. The follow-up time was more than 6 months. At the end of the follow-up, patients' contrast sensitivity (CS), reading acuity, reading speed and visual quality questionnaire results were assessed. The main statistical methods were two-way repeated measures analysis of variance, independent sample t-test, one-way analysis of variance and Kruskal-Wallis test. Results: There were no significant differences in gender distribution, age, or follow-up time between the control and high myopia groups, the control and high myopia subgroup, or the super high myopia subgroup (all P>0.05). At the end of the follow-up, the uncorrected distance, intermediate and near visual acuity of the super high myopia subgroup was 0.07±0.11, 0.34±0.08 and 0.20±0.09, respectively. The difference in postoperative visual acuity was not statistically significant (all P>0.05). The CS and CS with glare of the high myopia group (3 cpd: 1.48±0.18, 1.42±0.16; 6 cpd: 1.75±0.18, 1.76±0.15; 12 cpd: 1.44±0.24, 1.43±0.19; 18 cpd: 0.90±0.23, 0.85±0.20) were significantly different from the control group (3 cpd: 1.66±0.18, 1.62±0.16; 6 cpd: 1.88±0.14, 1.85±0.11; 12 cpd: 1.54±0.18, 1.53±0.14; 18 cpd: 1.06±0.18, 1.01±0.15) (P<0.05), except at 12 cpd (P=0.05). The CS and CS with glare of the super high myopia subgroup (3 cpd: 1.39±0.21, 1.31±0.13; 6 cpd: 1.66±0.16, 1.64±0.12; 12 cpd: 1.32±0.23, 1.31±0.18; 18 cpd: 0.75±0.16, 0.73±0.15) were worst (all P<0.05). A significant difference between the high myopia subgroup and the control group was only found at 3 cpd (1.53±0.13 vs. 1.66±0.18, 1.50±0.13 vs. 1.62±0.16; both P<0.05). The reading acuity and reading speed of the super high myopia subgroup were lower than the high myopia subgroup and the control group, while the differences were not statistically significant (all P>0.05). The questionnaire survey showed that there was no significant difference in the proportion of glare and halo between the two subgroups and the control group (both P>0.05). No patients reported dissatisfaction. The rate of glasses independents was 11/12 in the super high myopia subgroup, 15/17 in the high myopia subgroup and 31/33 in the control group, with no significant difference (P>0.05). Conclusions: The rotational asymmetric refractive intraocular lens is suitable for patients with high myopia and cataract, and has good far and near vision after operation. However, it could result in relatively low CS for super high myopia patients, so rigorous preoperative examination must be done. (Chin J Ophthalmol, 2021, 57: 358-365).

[An investigation of musculoskeletal disorders at multiple sites and related influencing factors among workers in an automobile assembly shop].

Objective: To investigate the current status of work-related musculoskeletal disorders (WMSDs) in automobile assembly workers, as well as the distribution of WMSDs at multiple sites and related influencing factors. Methods: From March to July 2019, cluster sampling was performed to select 663 male automobile assembly workers as respondents, and the musculoskeletal injury questionnaire was used to investigate their general status and working condition. A multinomial logistic regression analysis was used to analyze the influencing factors for WMSDs at multiple sites. Results: The detection rate of WMSDs within the past 7 days was 37.9% (251/663) among the automobile assembly workers, and the detection rate of WMSDs within the past 1 year was 51.9% (344/663) . Of all workers, 13.6% (90/663) had WMSDs involving only 1 site, while 38.3% (254/663) had WMSDs involving 2 or more sites. The multinomial logistic regression analysis showed that frequent turns during work was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites (odds ratio [OR]=1.65, 2.47, and 3.65, respectively) . Repeated action of lower extremities and ankles was a risk factor for WMSDs involving 4-6 and 7-9 sites (OR=2.15 and 2.98, respectively) . Working in an uncomfortable position was a risk factor for WMSDs involving 1-3, 4-6, and 7-9 sites (OR=1.95, 2.67, and 3.04, respectively) . Prolonged standing during work was a risk factor for WMSDs involving 1-3 and 4-6 sites (OR= 1.87 and 1.79, respectively) . Working overtime was a risk factor for WMSDs involving 7-9 sites (OR=5.48) . Adequate time for rest was a protective factor against WMSDs involving 1-3 and 4-6 sites (OR=0.50 and 0.31, respectively) . Conclusion: There is a high detection rate of WMSDs in automobile assembly workers, and WMSDs at multiple sites are more common than WMSDs at a single site. Poor position and organizational management factors are risk factors for occupational WMSDs at multiple sites.

Pathophysiological dissociation of the interaction between time pressure and trait anxiety during spatial orientation judgments.

Spatial orientation is achieved by integrating visual, vestibular and proprioceptive cues. Individuals that rely strongly upon visual cues to facilitate spatial orientation are termed visually dependent. Heightened visual reliance commonly occurs in patients following vestibular dysfunction and can influence clinical outcome. Additionally, psychological factors, including anxiety, are associated with poorer clinical outcome following vestibular dysfunction. Given that visual dependency measures are affected by psychological and contextual influences, such as time pressure, we investigated the interaction between time pressure and anxiety upon visual dependency in healthy controls and vestibular migraine patients. Visual dependency was assessed using a "Rod and Disk" task at baseline and under time pressure (3 s to complete the task). Non-situational (trait) and situational (state) anxiety levels were quantified using the Spielberg State-Trait Anxiety Inventory. We calculated the change in visual dependency (VD) [∆VD = VDtime pressure  - VDbaseline ] and correlated it with participants' trait anxiety scores. We observed a significant negative correlation between trait anxiety and the change in VD (R2  = .393, p < .001) in healthy controls and a positive correlation in dizzy patients (R2  = .317, p < .001). That is, healthy individuals that were more anxious became less visually dependent under time pressure (i.e., more accurate), whereas less anxious individuals became more visually dependent. The reverse was observed in vestibular migraine patients. Our results illustrate that anxiety can differentially modulate task performance during spatial orientation judgements under time pressure in healthy individuals and dizzy patients. These findings have potential implications for individualised patient rehabilitation therapies.

P-type laser-doped WSe2/MoTe2 van der Waals heterostructure photodetector.

Van der Waals heterostructures (vdWHs) based on two-dimensional (2D) materials are being studied extensively for their prospective applications in photodetectors. As the pristine WSe2/MoTe2 heterostructure is a type I (straddling gap) structure, it cannot be used as a photovoltaic device theoretically, although both WSe2 and MoTe2 have excellent photoelectric properties. The Fermi level of p-doped WSe2 is close to its valence band. The p-doped WSe2/MoTe2 heterostructure can perform as a photovoltaic device because a built-in electric field appears at the interface between MoTe2 and p-doped WSe2. Here, a 633 nm laser was used for scanning the surface of WSe2 in order to obtain the p-doped WSe2. x-ray photoelectron spectroscopy (XPS) and electrical measurements verified that p-type doping in WSe2 is produced through laser treatment. The p-type doping in WSe2 includes substoichiometric WOx and nonstoichiometric WSex. A photovoltaic device using p-doped WSe2 and MoTe2 was successfully fabricated. The band structure, light-matter reactions, and carrier-transport in the p-doped WSe2/MoTe2 heterojunction were analyzed. The results showed that this photodetector has an on/off ratio of ≈104, dark current of ≈1 pA, and response time of 72 µs under the illumination of 633 nm laser at zero bias (V ds = 0 V). The proposed p-doping method may provide a new approach to improve the performance of nanoscale optoelectronic devices.

Death-inducer obliterator 1 (DIDO1) silencing suppresses growth of bladder cancer cells through decreasing SAPK/JNK signaling cascades.

Death inducer obliterator (DIDO) is involved in apoptosis and embryonic stem cell self-renewal. Here, we investigate the effect of DIDO1 on bladder cancer cells and clarify the underlying molecular mechanism. Bladder cancer tissues and cell lines (T24, ScaBER, 5637), as well as normal bladder epithelial cells (SV-HUC-1), were used to measure the levels of DIDO1 mRNA and protein by qRT-PCR and western blot, respectively. The results indicated that DIDO1 was highly expressed in bladder cancer tissues and cell lines. And the expression of DIDO1 in T24 and 5637 cells was higher than that in ScaBER and SV-HUC-1 cells. The expression of DIDO1 was knocked down in T24 and 5637 cells by infection with shDIDO1-1 and shDIDO1-2 lentivirus. The growth of T24 and 5637 cells was monitored using Celigo, MTT assays, and colony formation assay. Apoptosis was examined by flow cytometric analysis. The effect of DIDO1 knockdown on tumorigenesis of T24 xenograft tumors was determined in nude mice. Reduction of DIDO1 mRNA resulted in reduced proliferation, decreased cell colony formation, increased apoptosis in vitro, and inhibited tumorigenesis in vivo. Furthermore, we identified signaling molecules involved in stress and apoptosis using the PathScan Antibody Array Kit and western blot. The depletion of DIDO1 significantly decreased the levels of phosphorylated SAPK/JNK, and Chk1/2, as well as the upregulating cleaved Caspase-7 expression. These results indicated that the potential mechanism of DIDO1 action might involve SAPK/JNK signaling cascades.

[The proatherogenic effect of high salt diet combined with focal hypoperfusion on spontaneous hypertension rat].

Objective: To explore the histopathology, monocytes phenotypes and brain mRNA transcription of angiogenic and atherogenic factors preliminarily in spontaneous hypertensive rats (SHRs) fed with high salt diet and subjected to chronic focal hypoperfusion. Methods: A total of 21 SHRs were randomly assigned into SHR with normal diet (SHR-ND group, n=7), SHR fed with high salt (8%) chows (SHR-HSD group, n=14) groups. After induction of high salt diet for 20 weeks, unilateral carotid artery occlusion was applied to one half of SHR-HSD (SHR-HSD-UCAO, n=7) group for 10 weeks to mimic chronic focal cerebral hypoperfusion. The neuropathology, monocytes phenotypes and brain transcription of fibroblast growth factor (FGF-b), platelet-derived endothelial cell growth factor (PD-ECGF), angiogenin (ANG), transforming growth factor-ß (TGF-ß) and vascular endothelial growth factor A (VEGF-A) among three groups were compared. Results: The systolic blood pressure ((246±12) mmHg vs (220±16) mmHg, P=0.0291, 1 mmHg=0.133 kPa) and diastolic blood pressure ((189±15) mmHg vs (164±12) mmHg, P=0.0143) of SHR-HSD group were elevated significantly compared with those of SHR-ND group. Compared with normotensive Wistar-Kyoto (WKY), SHR-ND, SHR-HSD and SHR-HSD-UCAO groups demonstrated lipohyalinosis, vessel wall thickening, lumen narrowing and multiple enlarged perivascular space and diffuse disarrangement of nerve fiber and myelin vacuolation in corpus callosum pathologically. The ratio of CD11b(+) CD68(+) monocytes in peripheral blood of SHR-HSD group was higher compared with both SHR-ND and SHR-HSD-UCAO groups (P=0.000 8). The mean inflorescence index (MFI) of CD86 and CD206 showd considerable decline in SHR-HSD-UCAO group compared with those of SHR-HSD group (P=0.018 7 and 0.016 8, respectively). The CD86 MFI of CD11b+CD68+ monocytes in SHR-HSD-UCAO group was remarkably higher than that of SHR-ND and SHR-HSD groups (P=0.000 5). Compared with SHR-ND and SHR-HSD groups, the brain mRNA transcription of angiogenic factors including PD-ECGF and ANG were down-regulated (P=0.004 6 and 0.000 2, respectively), while the atherogenic factors including TGF-ß and VEGF-A were up-regulated in SHR-HSD-UCAO group (P<0.000 1 and P=0.045, respectively). Conclusion: SHR-HSD-UCAO group shares the pathophysiological characteristics with advanced stage arteriosclerotic cerebral small vessel disease (aCSVD), including neuropathology, imbalanced circulating monocytes phenotypes and down-regulated angiogenic factors.

Blood-derived amyloid-ß protein induces Alzheimer's disease pathologies.

The amyloid-ß protein (Aß) protein plays a pivotal role in the pathogenesis of Alzheimer's disease (AD). It is believed that Aß deposited in the brain originates from the brain tissue itself. However, Aß is generated in both brain and peripheral tissues. Whether circulating Aß contributes to brain AD-type pathologies remains largely unknown. In this study, using a model of parabiosis between APPswe/PS1dE9 transgenic AD mice and their wild-type littermates, we observed that the human Aß originated from transgenic AD model mice entered the circulation and accumulated in the brains of wild-type mice, and formed cerebral amyloid angiopathy and Aß plaques after a 12-month period of parabiosis. AD-type pathologies related to the Aß accumulation including tau hyperphosphorylation, neurodegeneration, neuroinflammation and microhemorrhage were found in the brains of the parabiotic wild-type mice. More importantly, hippocampal CA1 long-term potentiation was markedly impaired in parabiotic wild-type mice. To the best of our knowledge, our study is the first to reveal that blood-derived Aß can enter the brain, form the Aß-related pathologies and induce functional deficits of neurons. Our study provides novel insight into AD pathogenesis and provides evidence that supports the development of therapies for AD by targeting Aß metabolism in both the brain and the periphery.