Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Invasive fungal infections threaten the lives and health of humans, especially immunodeficient patients or hospitalized patients with serious underlying diseases, and impose a heavy economic burden on society. The emergence of drug-resistant fungi, the formation of biofilms, and the limits and side effects of existing antifungal drugs increase the difficulty of clinical treatment, and there is an urgent need for the development of novel antifungal drugs. Therefore, based on previous kinase chemical library antifungal activity screening studies, this paper further investigates the activity of anaplastic lymphoma kinase (ALK) inhibitor 3-[5-chloro-2-({2-methoxy-4-[4-(4-methylpiperazin-1-yl)hexahydropyridin-1-yl]phenyl}amino)pyrimidin-4-yl]-1H-indole (HG-14-10-04, HG) against various fungi and elucidates its mechanism of action. The in vitro antifungal activity of HG was evaluated by micro liquid-dilution method, time-killing curve, mycelium formation and biofilm formation assays. The results showed that HG exhibited inhibitory and even fungicidal effects against sensitive and resistant Candida albicans, Candida krusei, Cryptococcus neoformans, Candida tropicalis, Candida glabrata and Candida parapsilosis (MICs = 8-16 μg·mL^-1); HG significantly inhibited the mycelium and biofilm formation, and destroyed the mature biofilm; and it exhibited synergistic antifungal effects with amphotericin B. The antifungal mechanism of HG was investigated by flow cytometry and transmission electron microscopy, etc. Sequencing analysis showed a total of 1 041 differentially expressed genes, of which 666 were up-regulated and 375 were down-regulated. According to the GO functional classification results, the up-regulated genes were mainly involved in ribosome production, oxidation-reduction and other functions, while the down-regulated genes were mainly involved in the synthesis of carbohydrate, glycoproteins, glycolipids and their metabolism, GPI anchor synthesis, and cytoskeleton and other functions. In addition, HG could significantly increase the level of reactive oxygen species (ROS), induce the fungal necrosis, block the cell cycle at the G0/G1 phase, and change the ultrastructure of the fungi, especially the structure of the fungal cell wall. Therefore, the enhanced inhibitory and fungicidal activity of HG may be related to the elevation of ROS, alteration of cellular ultrastructure (especially cell wall structure) and cell cycle arrest at the G0/G1 phase. Further optimization of its structure will provide a basis for the discovery of novel antifungal drugs or lead compounds.

OBJECTIVE To evaluate the effectiveness， safety， economy， innovation， suitability and accessibility of recombinant Mycobacterium tuberculosis fusion protein （EC）， and to provide evidence for selecting skin detection methods for tuberculosis infection diagnosis and auxiliary diagnosis of tuberculosis. METHODS The effectiveness and safety of EC compared with purified protein derivative of tuberculin （TB-PPD） were analyzed by the method of systematic review. Cost minimization analysis， cost-effectiveness analysis and cost-utility analysis were used to evaluate the short-term economy of EC compared with TB-PPD， and cost-utility analysis was used to evaluate the long-term economy. The evaluation dimensions of innovation， suitability and accessibility were determined by systematic review and improved Delphi expert consultation， and the comprehensive score of EC and TB-PPD in each dimension were calculated by the weight of each indicator. RESULTS The scores of effectiveness， safety， economy， innovation and suitability of EC were all higher than those of TB-PPD. The affordability scores of the two drugs were consistent， while the availability score of EC was lower than those of TB-PPD. After considering dimensions and index weight， the scores of effectiveness， safety， economy， innovation， suitability， accessibility and the comprehensive score of EC were all higher than those of TB-PPD. CONCLUSIONS Compared with TB-PPD， EC performs better in all dimensions of effectiveness， safety， economy， innovation， suitability and accessibility. However， it is worth noting that EC should further improve its availability in the dimension of accessibility.

Objective:To investigate the effect of ship-shaped expanded polytetrafluoroethylene (e-PTFE) nasal prosthesis in rhinoplasty.Methods:From February 2016 to June 2021, 86 patients, including 9 males and 77 females, aged 18-47 (24±5) years old, were admitted to Chengdu High-tech Zone Xinyuerong Medical Aesthetic Clinic for cosmetic treatment of rhinoplasty. All patients underwent rhinoplasty with the application of ship-shaped e-PTFE and autologous cartilage. The postoperative complications, glabellar fullness, inverted brow triangle, nasal polygon aesthetic shape and patient satisfaction were evaluated. These data were measured and analyzed, including the nasal length, nasal tip height, nasal frontal angle and nasal facial angle before and after the operation.Results:In 86 patients, the incision healed in one stage after surgery, and 8 cases had nasal vestibular scar hyperplasia. All patients were followed up for 1-5 years: 84 cases obtained satisfactory nasal morphology, and 2 cases recovered naturally after adjusting and lowering the prosthesis height half a year after surgery because the interbrow area was too full. 74 patients (86%) were very satisfied, 10 cases (11.6%) were satisfied. The nasal length was (4.07±0.20) cm, the nasal tip height was (2.66±0.36) cm, the nasal frontal angle was (106.42±8.04)°, and the nasal face angle was (15.90±0.85)°before operation. The nasal length was (4.23±0.20) cm, the nasal tip height was (2.59±0.26) cm, the naso-frontal angle was (113.69±6.34)°, and the naso-facial angle was (21.57±0.78)° at eighteen months after operation. There were statistically significant differences in nasal length, naso-frontal angle and naso-facial angle ( t=-5.51, -5.96, -52.31, P<0.01), but no statistically significant differences in nasal tip height ( t=1.47, P=0.146). Conclusions:The ship-shaped e-PTFE can be shaped to reflect the aesthetic of the nose dorsum, which is similar to the anatomical structure of the nose dorsum, increase the stability and authenticity of the prosthesis, and is worthy of clinical application.

OBJECTIVES: To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China. METHODS: A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups. RESULTS: Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05). CONCLUSIONS There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.
Bronchopulmonary Dysplasia/epidemiology* ; Female ; Gestational Age ; Humans ; Infant ; Infant, Extremely Premature ; Infant, Newborn ; Pregnancy ; Respiratory Distress Syndrome, Newborn/epidemiology* ; Retrospective Studies ; Treatment Outcome

Objective:To explore the predictive factors for prepatellar subfascial gas in patients with closed patellar fracture and their impacts on the early infection following internal fixation.Methods:A retrospective analysis was performed in the 148 patients with closed patellar fracture who had been treated at Department of Orthopaedic Surgery, Zhangjiagang Hospital Affiliated to Soochow University from January 2018 through December 2021. All patients underwent preoperative three-dimensional CT examination of the knee joint and was treated by open reduction and internal fixation of patellar fractures. According to the presence or absence of gas in the prepatellar fascia, the patients were divided into 2 groups. In the gas group of 18 patients, there were 12 males and 6 females with an age of (58.3±14.5) years; in the gas-free group of 130 patients, there were 57 males and 73 females with an age of (60.5±14.6) years. The risk factors for prepatellar subfascial gas were screened out by comparing the gender, age, body mass index, injury mechanism, AO/OTA classification, diabetes, primary hypertension, neutrophil percentage, lymphocyte percentage, white blood cell count, neutrophil count, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, procalcitonin, and albumin before operation between the 2 groups. A receiver operating characteristic (ROC) curve for risk factors were made to identify the best screening points. The impacts of prepatellar subfascial gas were analyzed on early infection after internal fixation.Results:The preoperative neutrophil percentage was the risk factor for prepatellar subfascial gas ( P<0.05). The area under the ROC curve of preoperative neutrophil percentage for prediction of prepatellar subfascial gas was 0.700 (95% CI: 0.554 to 0.847), the optimal critical value was 78.45%, and the sensitivity and specificity were 0.556 and 0.831, respectively ( P=0.006). In the gas group, the incidence of early postoperative infection was insignificantly higher ( P=0.058) , but the time for postoperative antibiotic use was significantly longer and the dressing changes were significantly more frequent than those in the gas-free group ( P<0.05). Conclusions:In patients with closed patellar fracture, preoperative neutrophil percentage >78.45% can be used as an effective non-imaging indicator for prepatellar subfascial gas. A patient with prepatellar subfascial gas could be more prone to early postoperative infection.

OBJECTIVE: To observe the effect of horizontal penetration needling at vertigo auditory area and balance area on residual dizziness after successful repositioning maneuver in patients with benign paroxysmal positional vertigo (BPPV). METHODS: Sixty-six patients with residual dizziness after successful repositioning maneuver for BPPV were randomly divided into an observation group (34 cases, 1 case dropped off) and a control group (32 cases, 2 cases dropped off). The patients in the observation group were treated with horizontal penetration needling at vertigo auditory area and balance area, once every other day; three times were taken as a course of treatment, and two courses of treatment were given. The patients in the control group received no acupuncture and medication. The dizziness handicap inventory (DHI) and visual analogue scale (VAS) scores were observed before treatment and after 1 and 2 courses of treatment. RESULTS: Except for the emotional score of DHI in the control group after 1 course of treatment, the sub item scores and total scores of DHI and VAS scores in the two groups after treatment were lower than those before treatment ( CONCLUSION Whether acupuncture or not, residual dizziness after repositioning maneuver for BPPV can be relieved within 2 weeks; horizontal penetration needling at vertigo auditory area and balance area could improve dizziness symptoms and shorten the course of disease.
Benign Paroxysmal Positional Vertigo/therapy* ; Dizziness/therapy* ; Humans ; Patient Positioning ; Vascular Surgical Procedures

OBJECTIVES: To study the effect of glucose metabolism disorders on the short-term prognosis in neonates with asphyxia. METHODS: A retrospective analysis was performed on the medical data of the neonates with asphyxia who were admitted to 52 hospitals in Hubei Province of China from January to December, 2018 and had blood glucose data within 12 hours after birth. Their blood glucose data at 1, 2, 6, and 12 hours after birth (with an allowable time error of 0.5 hour) were recorded. According to the presence or absence of brain injury and/or death during hospitalization, the neonates were divided into a poor prognosis group with 693 neonates and a good prognosis group with 779 neonates. The two groups were compared in the incidence of glucose metabolism disorders within 12 hours after birth and short-term prognosis. RESULTS: Compared with the good prognosis group, the poor prognosis group had a significantly higher proportion of neonates from secondary hospitals (48.5% vs 42.6%, CONCLUSIONS Recurrent hyperglycemia in neonates with asphyxia may suggest poor short-term prognosis, and it is necessary to strengthen the early monitoring and management of the nervous system in such neonates.
Asphyxia ; Asphyxia Neonatorum/epidemiology* ; Humans ; Hyperglycemia ; Infant, Newborn ; Prognosis ; Retrospective Studies

Objective:To evaluate the safety and effectiveness of tranexamic acid in the treatment of spontaneous intracerebral hemorrhage.Methods:Patients with spontaneous intracerebral hemorrhage admitted to the Departments of Emergency and Neurology, Nanjing Drum Tower Hospital from December 2015 to December 2018 were enrolled prospectively. The patients were randomly divided into two groups according to a random number table: tranexamic acid group and control group. All patients received conventional treatment. On this basis, 1 g of tranexamic acid injection was given to the tranexamic acid group, dissolved in 100 ml of normal saline, intravenous injection for 10 min; then 1 g of tranexamic acid was given, dissolved in 250 ml of normal saline, intravenous drip for 8 h. The control group was given an equal volume of normal saline. The main outcome measures were good outcome (defined as modified Rankin Scale score0-2) and mortality at 90 d after treatment. The secondary outcome was hematoma enlargement at 24 h after treatment and the National Institutes of Health Stroke Scale (NIHSS) score at 7 and 30 days after treatment. Platelet count and fibrinogen level were measured before treatment and 4 h after the infusion of tranexamic acid. Various adverse events were monitored.Results:A total of 150 patients were included, including 83 males (55.3%). There were 73 patients in the tranexamic acid group and 77 in the control group. There was no statistically significant difference in baseline data between the two groups. The rate of good outcome in the tranexamic acid group at 90 d was significantly higher than that in the control group (57.5% vs. 40.3%; χ2=4.476, P=0.034), while there were no significant differences in mortality rate (0% vs. 1.3%; Fisher's exact test P=1.000) and the proportion of patients with hematoma enlargement at 24 h (6.8% vs. 15.6%; χ2=2.845, P=0.092). The NIHSS score at 7 d (9.26±3.35 vs. 11.68±4.25; t=3.859, P<0.001) and at 30 d (5.45±2.52 vs. 7.38±3.28; t=4.030, P<0.001) in the tranexamic acid group were significantly lower than those of the control group. Fibrinogen in the tranexamic acid group increased significantly after treatment compared with baseline (4.20±0.56 g/L vs. 3.33±0.60 g/L; t=8.997, P<0.001), and was significantly higher than that in the control group after treatment (4.20±0.56 g/L vs. 3.30±0.55 g/L; t=9.906, P<0.001). No adverse events such as venous thromboembolism, ischemic events, and seizures were observed. Conclusion:Tranexamic acid can promote the recovery of neurological function, and improve the outcome of patients with acute spontaneous intracerebral hemorrhage, and the safety is good.