Recent advances in bacterial cellulose-based antibacterial composites for infected wound therapy.

Wound infection arising from pathogenic bacteria brought serious trouble to the patient and medical system. Among various wound dressings that are effective in killing pathogenic bacteria, antimicrobial composites based on bacterial cellulose (BC) are becoming the most popular materials due to their success in eliminating pathogenic bacteria, preventing wound infection, and promoting wound healing. However, as an extracellular natural polymer, BC is not inherently antimicrobial, which means that it must be combined with other antimicrobials to be effective against pathogens. BC has many advantages over other polymers, including nano-structure, significant moisture retention, non-adhesion to the wound surface, which has made it superior to other biopolymers. This review introduces the recent advances in BC-based composites for the treatment of wound infection, including the classification and preparation methods of composites, the mechanism of wound treatment, and commercial application. Moreover, their wound therapy applications include hydrogel dressing, surgical sutures, wound healing bandages, and patches are summarized in detail. Finally, the challenges and future prospects of BC-based antibacterial composites for the treatment of infected wounds are discussed.

General temporal ghost imaging model with detection resolution and noise.

Improving imaging quality while reducing the sampling time simultaneously is a crucial challenge that limits the practical application of temporal ghost imaging (TGI). To improve the performance of TGI, various methods have been proposed and verified. However, a work analyzing in detail the influence of intensity accuracy and detection noise of TGI is still absent. Here, we establish an evaluation model to quantify the imaging quality of TGI and differential TGI (DTGI). Our model considers the intensity detection accuracy, threshold, and noise of the test path during image reconstruction and quantifies their influences by developing general imaging formulas of (D)TGI. We also simulate the imaging of (D)TGI numerically. The evaluation demonstrates that (D)TGI is relatively not sensitive to detection accuracy and thresholds of the test path, and image quality is degraded slightly even when those parameters turn much worse. (D)TGI is relatively robust to detection noise but will be unable to reconstruct the object when noise is too strong. DTGI does not show clear advantages over TGI. Our work develops an effective model to quantify the image quality with practical parameters and is significant to real applications of (D)TGI.

Efficacy and safety of VRD regimen of autologous hematopoietic stem cell transplantation in patients with newly diagnosed multiple myeloma / 中华内科杂志

Objective: To explore the stem cell collection rate and efficacy and safety of patients aged 70 and below with newly diagnosed multiple myeloma (MM) treated with the VRD (bortezomib, lenalidomide and dexamethasone) regimen followed by autologous stem cell transplantation (ASCT). Methods: Retrospective case series study. The clinical data of 123 patients with newly diagnosed MM from August 1, 2018, to June 30, 2020, at the First Affiliated Hospital of Soochow University and Suzhou Hopes Hematology Hospital, who were eligible for VRD regimen sequential ASCT, were collected. The clinical characteristics, efficacy after induction therapy, mobilization regimen of autologous stem cells, autologous stem cell collection rate, and side effects and efficacy of ASCT were retrospectively analyzed. Results: Of the 123 patients, 67 were males. The median patient age was 56 (range: 31-70) years. Patients with IgG, IgA, IgD, and light-chain types accounted for 47.2% (58/123), 23.6% (29/123), 3.2% (4/123), and 26.0% (32/123) of patients, respectively. In addition, 25.2% (31/123) of patients had renal insufficiency (creatinine clearance rate<40 ml/min). Patients with Revised-International Staging System (R-ISS) Ⅲ accounted for 18.2% (22/121) of patients. After induction therapy, the rates of partial response and above, very-good partial response (VGPR) and above, and complete response (CR)+stringent CR were 82.1% (101/123), 75.6% (93/123), and 45.5% (56/123), respectively. Overall, 90.3% (84/93) of patients were mobilized with cyclophosphamide+granulocyte colony-stimulating factor (G-CSF) and 8 patients with G-CSF or G-CSF+plerixafor due to creatinine clearance rate<30 ml/min and one of them was mobilized with DECP (cisplatin, etoposide, cyclophosphamide and dexamethasone)+G-CSF for progressive disease. The rate of autologous stem cell collection (CD34+cells≥2×106/kg) after four courses of VRD regimen was 89.1% (82/92), and the rate of collection (CD34+cells≥5×106/kg) was 56.5% (52/92). Seventy-seven patients treated with the VRD regimen sequential ASCT. All patients had grade 4 neutropenia and thrombocytopenia. Among the nonhematologic adverse events during ASCT, the highest incidence was observed for gastrointestinal reactions (76.6%, 59/77), followed by oral mucositis (46.8%, 36/77), elevated aminotransferases (44.2%, 34/77), fever (37.7%, 29/77), infection (16.9%, 13/77) and heart-related adverse events (11.7%, 9/77). Among the adverse events, grade 3 adverse events included nausea (6.5%, 5/77), oral mucositis (5.2%, 4/77), vomiting (3.9%, 3/77), infection (2.6%, 2/77), elevated blood pressure after infusion (2.6%, 2/77), elevated alanine transaminase (1.3%, 1/77), and perianal mucositis (1.3%, 1/77); there were no grade 4 or above nonhematologic adverse events. The proportion of patients who achieved VGPR and above after VRD sequential ASCT was 100% (75/75), and the proportion of patients who were minimal residual disease-negative (<10-4 level) was 82.7% (62/75). Conclusion: In patients aged 70 and below with newly diagnosed MM treated with VRD induction therapy, the collection rate of autologous stem cells was good, and good efficacy and tolerability were noted after follow-up ASCT.

Leukemia Genotype Analysis of Children with Acute Lymphoblastic Leukemia in Yunnan Area / 中国实验血液学杂志

OBJECTIVE@#To analyze 43 leukemia genes in children with acute lymphoblastic leukemia (ALL) in Yunnan province, and provide the basis for the diagnosis and treatment of children with ALL in this area.@*METHODS@#The clinical data of 428 children with newly diagnosed ALL in Yunnan area from January 2015 to December 2020 were retrospectively analyzed. Multiple nested PCR technology was used to detect 43 common leukemia genes.@*RESULTS@#Among the 428 children with ALL, 159 were positive for leukemia genes, with a positive rate of 37.15% (159/428), and a total of 15 leukemia genes were detected. Among the 159 leukemia gene-positive children, ETV6-RUNX1+ accounted for 25.79% (41/159), followed by E2A-PBX1+ and BCR-ABL+, accounting for 24.53% (39/159) and 23.27% (37/159) respectively. MLL+ accounted for 6.29% (10/159), WT1+ accounted for 4.40% (7/159), IKZF1 gene deletion and CRLF2+ accounted for 3.77% (6/159) respectively. The positive rate of MLL (46.15%) was the highest in ＜1-year old group, the positive rate of ETV6-RUNX1 (10.56%) was the highest in 1-10-year old group, and BCR-ABL+ rate (23.65%) was the highest in >10-year old group. The distribution of leukemia genes in different age groups was statistically significant (P <0.05).@*CONCLUSION@#The most common fusion gene of children with ALL in Yunnan is ETV6-RUNX1, followed by E2A-PBX1 and BCR-ABL.

A simple method for eyelid reconstruction with an advancement flap after resection of a minor nevus on the eyelid margin.

We developed a simple and effective method for eyelid reconstruction after resection of a minor nevus on the eyelid margin. With a vertical advancement flap to repair the defect, all patients were satisfied with the cosmetic and functional results of the eyelids, and no significant complications occurred.

Effect of Jiedu Huayu Granules on Inflammatory State of Patients with Chronic Hepatic Failure with Toxic Heat and Stasis Syndrome / 中国实验方剂学杂志

ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity / 中华内分泌代谢杂志

Objective:Explore the relationship between sleep duration, sleep time and brachial-ankle pulse wave velocity(baPWV) in community population.Methods:Questionnaire, physical examination, blood tests, and baPWV detection were applied to a community based population. Finally, 3 912 subjects with complete data were included in the study. The relationship between sleep duration, time to fall asleep and PWV was evaluated with binary logistic regression analysis. Results:Being adjusted for age, sex, prevalence of diabetes, sleep condition, body mass index, blood glucose, blood pressure, dyslipidemia, ankle-brachial index, sleep duration and time to fall asleep were correlated with PWV. The risk of PWV abnormalities was increased in the≥8 h group compared to the 6-8 h group( OR=1.155, 95% CI 0.995-1.367, P=0.037). The risk of abnormalities PWV was higher in the group with sleep time after 00: 00 than in the group -23: 00( OR=1.482, 95% CI 1.008-2.179, P=0.045). Conclusion:Long sleep duration(≥8 h) and late sleep time(after 00: 00) may be associated with higher risk of atherosclerosis.

Effects of massive blood transfusion on serum electrolyte balance and inflammatory factor levels in patients with severe trauma / 中国基层医药

Objective:To investigate the effects of massive blood transfusion on serum electrolyte balance and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in patients with severe trauma.Methods:A total of 83 patients with severe trauma who received treatment in Eastern District of LiHuili Hospital, Ningbo Medical Center between July 2019 and December 2020 were included in this study. All of them underwent blood transfusion. They were divided into massive blood transfusion group ( n = 29) and general blood transfusion group ( n = 54) according to the volume of blood transfused. Changes in coagulation function, electrolyte, liver-kidney function and inflammatory factor levels pre- and post-blood transfusion were compared between massive blood transfusion and general blood transfusion groups. Results:At 1 day after blood transfusion, activated partial thromboplastin time (APTT) and prothrombin time (PT) in the massive blood transfusion group were (45.64 ± 2.78) seconds and (17.71 ± 2.08) seconds, respectively, which were significantly longer than those in the general blood transfusion group [(41.02 ± 2.80) seconds, (15.35 ± 1.72) seconds, t = 5.53, 7.18, P < 0.05). At 1 day after blood transfusion, levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the massive blood transfusion group were (1.84 ± 0.32) μg/L, (113.72 ± 13.34) ng/L, (28.94 ± 4.22) mg/L, respectively, which were significantly increased compared with those measured before blood transfusion [(1.28 ± 0.29) μg/L, (95.18 ± 10.64) ng/L, (16.48 ± 3.37) mg/L, t = 6.98, 5.85, 12.42, all P < 0.05]. Levels of tumor necrosis factor-α, interleukin-6 and C-reaction protein in the general blood transfusion group were (1.34 ± 0.27) μg/L, (98.54 ± 9.62) ng/L, (20.05 ± 3.30) mg/L, respectively at 1 day after blood transfusion, which were significantly increased compared with those measured before blood transfusion [(1.23 ± 0.26) μg/L, (94.22 ± 8.82) ng/L, (16.16 ± 3.39) mg/L, t = 2.15, 2.43, 6.04, all P < 0.05]. At 1 day after blood transfusion, serum levels of tumor necrosis factor-α and C-reaction protein in the massive blood transfusion group were significantly higher than those in the general blood transfusion group ( t = 7.53, 10.59, both P < 0.05). At 1 day after blood transfusion, serum levels of K + and Ca 2+ in the massive blood transfusion group were (3.56 ± 0.54) mmol/L and (1.87 ± 0.28) mmol/L, respectively, which were significantly lower than those in the general blood transfusion group [(4.27 ± 0.34) mmol/L, (2.26 ± 0.24) mmol/L, t = 7.34, 6.65, both P < 0.05]. Serum levels of alanine aminotransferase and aspartate aminotransferase in the massive blood transfusion group were (52.46 ± 20.27) U/L, (82.37 ± 31.15) U/L, respectively, which were significantly higher than those in the general blood transfusion group [(37.57 ± 10.31) U/L, (49.35 ± 10.14) U/L, t = 4.44, 7.14, both P < 0.05)]. The incidence of abnormal liver function in the massive blood transfusion group was significantly higher than that in the general blood transfusion group [62.07% (18/29) vs. 29.63% (16/54), χ2 = 10.13, P < 0.05)]. Conclusion:The internal environment of patients with severe trauma will change after massive blood transfusion. Their coagulation function, inflammatory factors, liver function and electrolyte balance should be monitored in time.

An N-Halamine/Graphene Oxide-Functionalized Electrospun Polymer Membrane That Inactivates Bacteria on Contact and by Releasing Active Chlorine.

The emergence of antibiotic-resistant "superbugs" in recent decades has led to widespread illness and death and is a major ongoing public health issue. Since traditional antimicrobials and antibiotics are in many cases showing limited or no effectiveness in fighting some emerging pathogens, there is an urgent need to develop and explore novel antibacterial agents that are both powerful and reliable. Combining two or more antibiotics or antimicrobials has become a hot topic in antibacterial research. In this contribution, we report on using a simple electrospinning technique to create an N-halamine/graphene oxide-modified polymer membrane with excellent antibacterial activity. With the assistance of advanced techniques, the as-obtained membrane was characterized in terms of its chemical composition, morphology, size, and the presence of active chlorine. Its antibacterial properties were tested with Escherichia coli (E. coli) as the model bacteria, using the colony-counting method. Interestingly, the final N-halamine/graphene oxide-based antibacterial fibrous membrane inactivated E. coli both on contact and by releasing active chlorine. We believe that the synergistic antimicrobial action of our as-fabricated fibrous membrane should have great potential for utilization in water disinfection, air purification, medical and healthcare products, textile products, and other antibacterial-associated fields.

Topical Timolol Combined Intralesional Injection of Diprospan in the Treatment of Elevated Localized Mixed Infantile Hemangiomas and a Discussion for Proper Timing for Injection.

BACKGROUND: Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. PURPOSE: To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. METHODS: Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. RESULTS: Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ±â€Š1.50 months (range: 1.00-6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. CONCLUSION: Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.

Pituitary adenoma with posterior area invasion of cavernous sinus: surgical anatomy, approach, and outcomes.

We found a series of Knosp grade 3A-4 pituitary adenomas in the posterior areas of the cavernous sinus (CS), a triangular-like structure on axial MRI. In this study, we dissected the surrounding neurovascular structure, discussed the surgical approach, and analyzed outcomes for patients with this invasion into this area. Eight embalmed adult cadaveric specimens were prepared for this study to demonstrate in detail the surgical anatomy related to this triangular-like structure. We used the "two points and one line" method to determine the surgical approach, and 35 cases with this area invasion were retrospectively reviewed. According to the endoscopic and microsurgical anatomy, the triangular-like structure appearing on the axial MRI is correlated with a square-based pyramid structure in the CS, and the upper surface is the posterior portion of the oculomotor triangle. A total of 37 posterior areas of the CS were involved in 35 patients. The accuracy of the "two points and one line" method in predicting the surgical approach is 86.5% (32/37). All three patients with Knosp 3A underwent gross total resection (GTR). Twenty (62.5%) patients with Knosp 4 underwent GTR, 9 (28.1%) patients underwent subtotal resection, and 3 (9.4%) patients underwent partial resection. Preoperative symptoms were alleviated to varying degrees, and no worsening occurred. Postoperative complications included two (5.7%) cases of cerebrospinal fluid leakage, one (2.9%) case of meningitis, two (5.7%) cases of permanent diabetes insipidus, and three (8.6%) cases of transient cranial nerve palsy. The "two points and one line" method is of great value in predicting the surgical approach of pituitary adenomas with CS invasion. The anatomic description of this particular square-based pyramid structure in the CS refines the understanding of pituitary adenomas with CS invasion.

Anatomical study of a surgical approach through the neck to the jugular foramen under endoscopy.

OBJECTIVES: To investigate the feasibility of an endoscopic surgical approach through the neck to the jugular foramen, to determine the relevant techniques and extent of exposure, and to provide a new surgical approach with minimal trauma. METHODS: Nine cadaveric head specimens with attached necks were fixed with 10% formalin solution. Two of the heads were fixed and injected with colored silicone rubber. Through the dissection of these cadaver head and neck specimens, we designed a surgical approach from the neck to the jugular foramen area with the use of a neuroendoscope and performed simulated surgery to determine which anatomical structures were encountered in the approach. RESULTS: The posterior aspect of the internal jugular vein is adjacent to the rectus capitis lateralis. The internal carotid artery is anteromedial to the internal jugular vein, with the glossopharyngeal nerve, accessory nerve, vagus nerve and hypoglossal nerve in between. Removal of the rectus capitis lateralis can reveal the jugular process, and exposing the space between the superior oblique muscle and the jugular process can reveal the atlanto-occipital joint. Drilling through the occipital condyle can facilitate entrance into the skull, expose the flank of the medulla oblongata, and reveal the medullary olive and accessory nerve, vagus nerve, hypoglossal nerve, vertebral artery and posterior inferior cerebellar artery. Removing the jugular vein and completely opening the posterior wall of the jugular foramen can expose the inferior wall of the jugular bulb and the inferior wall of the sigmoid sinus. Drilling through the styloid process, which is lateral to the internal jugular vein, can expose the lateral area and upper wall of the jugular bulb and cranial nerves (CN) IX-XII; and near the top of the jugular bulb, the tympanic cavity and the external auditory canal can be easily opened. CONCLUSION: Endoscopic surgical access from the neck to the jugular foramen is feasible. This surgical approach can simultaneously remove intracranial and extracranial tumors and can also be used to remove tumors in the ventral region of the occipital foramen and the hypoglossal canal. Furthermore, this approach is advantageous in that minimal trauma is inflicted. With judicious patient selection, this approach may have significant advantages and may be used as a primary or secondary surgical approach in the future. Nonetheless, this approach is still in development in a laboratory setting, and further research and improvements are needed before facing more complicated situations in clinical practice.

Pemetrexed-based chemotherapy for non-small-cell lung cancer patients with EGFR exon 20 insertion mutation: a multicenter study.

BACKGROUND: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied. METHODS: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins. RESULTS: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767_V769dupASV (33/119, 27.73%), S768_D770dupSVD (19/119, 15.97%), N771_H773dupNPH (11/119, 9.24%), A763_Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767_V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05). CONCLUSIONS: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins.

Upregulation of Connexin 40 Mediated by Nitric Oxide Attenuates Cerebral Vasospasm After Subarachnoid Hemorrhage via the Nitric Oxide-Cyclic Guanosine Monophosphate-Protein Kinase G Pathway.

OBJECTIVE: The present study was performed to elucidate the role of nitric oxide (NO) and connexin 40 (Cx40) in the induction of cerebral vasospasm after subarachnoid hemorrhage (SAH) in vivo. METHODS: A SAH rat model was established using the double-bleed method. A total of 108 Sprague-Dawley rats weighing 250-300 g were randomly divided into 6 groups: SAH; SAH plus diethylenetriamine (DETA)/NO (exogenous NO donor); SAH plus 8-bromoadenosine (8-Br)-cyclic guanosine monophosphate (cGMP; protein kinase G [PKG] activator); SAH plus DETA/NO plus KT5823 (PKG inhibitor); SAH plus DETA/NO plus 40Gap27 (Cx40 inhibitor); and sham. The changes in the diameter of the branch microvessels in the middle cerebral artery were recorded. The neurological score was evaluated using the Garcia scoring system. Basilar artery (BA) tension was measured using the Danish Myo Technology myograph system. Cx40 protein expression was analyzed using immunofluorescence and Western blotting. Endothelial NO synthase, soluble guanylate cyclase, and PKG protein expression were measured by Western blotting. RESULTS: A considerable narrowing of the cerebral vessels was detected in the SAH group compared with that in the sham group. Moreover, compared with the sham group, the SAH group showed a marked decrease in Cx40, endothelial NO synthase, soluble guanylate cyclase, and PKG expression. The expression of Cx40 and PKG were obviously higher in the SAH plus DETA/NO and SAH plus 8-Br-cGMP groups than in the SAH group. However, Cx40 was lower in the SAH plus DETA/NO plus KT5823 and SAH plus DETA/NO plus 40Gap27 groups than in the SAH plus ETA/NO group. The BAs showed significant vasodilation in the SAH plus DETA/NO and SAH plus 8-Br-cGMP groups. However, the vasodilation response of BAs was inhibited in the SAH plus DETA/NO plus KT5823 and SAH plus DETA-NO plus 40Gap27 groups. CONCLUSIONS: The NO-cGMP-PKG pathway alleviated cerebral vasospasm via Cx40 upregulation.

Mechanism of Traditional Chinese Medicine and Its Compound on Liver Fibrosis / 中国实验方剂学杂志

Hepatic fibrosis refers to the pathological process of abnormal proliferation of intrahepatic connective tissue caused by various pathogenic factors, resulting in the excessive accumulation of extracellular matrix (ECM) in the liver and the formation of fibrous scar. Its continuous deterioration will gradually develop into liver cirrhosis, liver failure, liver cancer and other serious liver diseases. Because liver fibrosis and early liver cirrhosis can be reversed, it is very important to control the reversible process of liver fibrosis for the prevention and treatment of liver cirrhosis and liver cancer. In recent years, it has been found that traditional Chinese medicine(TCM) has the characteristics of multi-target, less toxic and side effects and good effect in the treatment of liver fibrosis. In this paper, the mechanism of anti-hepatic fibrosis of TCM and its compound was summarized. TCM can regulate transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF), vascular endothelial growth factor (VEGF), connective tissue growth factor (CTGF) and other growth factors to inhibit the activation of (HSCs) and induce the apoptosis of activated HSCs, promote the expression of adiponectin and inhibit the secretion of leptin, inhibit the inflammatory reaction of liver, resist oxidant stress, inhibit the capillarization of hepatic sinusoidal endothelial cells, so as to effectively prevent the progress of liver fibrosis. Therefore, TCM can inhibit the development of liver fibrosis through multi-mechanism and multi-level, and is one of the important means to treat liver fibrosis.

Degradation enhancement of rice straw by co-culture of Phanerochaete chrysosporium and Trichoderma viride.

Straw is one of the most abundant stock of renewable biomass from crop production. However, its utilization efficiency is still very low. Although co-cultivation of fungi increases the degrading rate, the co-cultivation condition needs to be optimized. To optimize the co-culture condition of Phanerochaete chrysosporium and Trichoderma viride degrading rice straw, we first tested the antagonistic characteristic between the fungi. The results showed that the best co-culture pattern was to first inoculate P. chrysosporium and culture for 4 days, then inoculate T. viride, and co-culture the two fungi for 4 days. The optimum fermentation condition was 14% (w/v) of inoculum concentration, the equivalent inoculation of the fungi, culture temperature at 30 °C, and 1:1.4 for solid-liquid ratio. Under the optimum condition, the degradation ratios of lignin and cellulose were 26.38% and 33.29%, respectively; the soluble carbon content in the culture product was 23.07% (w/v). The results would provide important reference information for the efficient utilization of rice straw to produce more accessible energy resources, such as ethanol and glucose.

Electrospun Sesbania Gum-Based Polymeric N-Halamines for Antibacterial Applications.

Microorganism pollution induced by pathogens has become a serious concern in recent years. In response, research on antibacterial N-halamines has made impressive progress in developing ways to combat this pollution. While synthetic polymer-based N-halamines have been widely developed and in some cases even commercialized, N-halamines based on naturally occurring polymers remain underexplored. In this contribution, we report for the first time on a strategy for developing sesbania gum (SG)-based polymeric N-halamines by a four-step approach Using SG as the initial polymer, we obtained SG-based polymeric N-halamines (abbreviated as cSG-PAN nanofibers) via a step-by-step controllable synthesis process. With the assistance of advanced techniques, the as-synthesized cSG-PAN nanofibers were systematically characterized in terms of their chemical composition and morphology. In a series of antibacterial and cytotoxicity evaluations, the as-obtained cSG-PAN nanofibers displayed good antibacterial activity against Escherichia coli and Staphylococcus aureus, as well as low cytotoxicity towards A549 cells. We believe this study offers a guide for developing naturally occurring polymer-based antibacterial N-halamines that have great potential for antibacterial applications.

Sesbania Gum-Supported Hydrophilic Electrospun Fibers Containing Nanosilver with Superior Antibacterial Activity.

In this contribution, we report for the first time on a new strategy for developing sesbania gum-supported hydrophilic fibers containing nanosilver using electrospinning (SG-Ag/PAN electrospun fibers), which gives the fibers superior antibacterial activity. Employing a series of advanced technologies-scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, UV-visible absorption spectroscopy, X-ray photoelectron spectroscopy, and contact angle testing-we characterized the as-synthesized SG-Ag/PAN electrospun fibers in terms of morphology, size, surface state, chemical composition, and hydrophilicity. By adjusting the synthesis conditions, in particular the feed ratio of sesbania gum (SG) and polyacrylonitrile (PAN) to Ag nanoparticles (NPs), we regulated the morphology and size of the as-electrospun fibers. The fibers' antibacterial properties were examined using the colony-counting method with two model bacteria: Escherichia coli (a Gram-negative bacterium) and Staphylococcus aureus (a Gram-positive bacterium). Interestingly, compared to Ag/PAN and SG-PAN electrospun fibers, the final SG-Ag/PAN showed enhanced antibacterial activity towards both of the model bacteria due to the combination of antibacterial Ag NPs and hydrophilic SG, which enabled the fibers to have sufficient contact with the bacteria. We believe this strategy has great potential for applications in antibacterial-related fields.

Allogeneic CAR-T for treatment of relapsed and/or refractory multiple myeloma: four cases report and literatures review / 中华血液学杂志

Objective: To investigate the safety and efficacy of allogeneic CAR-T cells in the treatment of relapsed/refractory multiple myeloma (RRMM) . Methods: CAR-T cells were prepared from peripheral blood lymphocytes of HLA mismatch healthy donors. Median age was 55 (48-60) . Allogeneic cells were derived from 3 HLA haploidentical donors and 1 HLA completely mismatch unrelated donor. Four patients with RRMM were conditioned with FC regimen followed by CAR-T cell transfusion. They were infused into CART-19 (1×10(7)/kg on day 0) and (4.0-6.8) ×10(7)/kg CART-BCMA cells as split-dose infusions (40% on day 1 and 60% on day 2) . The adverse reactions and clinical efficacy were observed during follow-up after infusion, and the amplification and duration of CAR-T cells in vivo were monitored by PCR technique. Results: CAR-T cells were successfully infused in 3 of the 4 RRMM patients according to the study plan, and the infusion in one patient was delayed by 1 day due to high fever and elevated creatinine levels on day 3. The side effects included hematological and non-hematological toxicity, grade 3 hematological toxicity in 2 patients, grade 3 CRS in 1 one, grade 1 CRES in 1 one, prolonged APTT in 3 ones, tumor lysis syndrome in 1 one, mixed chimerism detected STR and clinical GVHD manifestation in 1 one. According to the efficacy criterias of IMWG, 2 patients acquired PR, 1 MR, and 1 SD respectively. Progression-free survival was 4 (3-5) weeks and overall survival was 63 (3-81) weeks. CAR T cells were amplified 2.2 (2-14) times in the patients with a median survival time of 10 (8-36) days. Conclusions: Small sample studies suggested that GVHD may be present in the treatment of RRMM with allogeneic CAR-T cells. There were early clinical transient events after transfusion. Low amplification and short duration of CAR-T cells in vivo may be the main factors affecting the efficacy.