Search

BackgroundNon-small cell lung cancer (NSCLC) with human epidermal growth factor receptor 2 (HER2) alterations poses a substantial treatment challenge. Current HER2-targeted therapies offer limited efficacy. Antibody-drug conjugates (ADCs) targeting HER2 have emerged as a promising therapeutic strategy. This study aimed to evaluate the clinical response to a novel ADC drug Disitamab vedotin (RC48) in advanced NSCLC with HER2 alterations.MethodsThis study conducted a retrospective review of patients harboring HER2 alterations treated with RC48 in the real world. Clinical outcomes were evaluated in terms of objective response rate (ORR), disease control rate (DCR), and progression-free survival (PFS).ResultsOut of 22 patients, 21 (95.5%) received RC48 combination therapy, while one received RC48 monotherapy. The ORR of all patients reached 45.5%, and the DCR stood at 90.9%. The median PFS (mPFS) was 7.5 months. Among patients receiving RC48 combination therapy, the ORR was 47.7%, and the mPFS of 8.1 months. The combination of RC48 with platinum+/- bevacizumab resulted in the highest ORR of 71.4% (5 out of 7 patients), with HER2 TKI following at a 50.0% ORR (4 out of 8 patients). First-line (1L) treatment with RC48 showed an ORR of 62.5% (5 out of 8 patients), second-line (2L) treatments had a 57.1% ORR (4 out of 7 patients), and beyond second-line (>2L) treatments exhibited a 14.3% ORR (1 out of 7 patients). Patients with 1L, 2L, or >2L treatment had a mPFS of 8.1 months, 7.2 months, and 7.4 months, respectively. Patients with HER2 mutations or amplifications, and those with concurrent mutations and amplifications at baseline, showed mPFS of 8.1 months, 9.4 months, and 7.4 months, respectively. The mPFS was significantly longer in patients with HER2 amplification. The most common adverse events included hand-foot syndrome (54.5%), asthenia (50.0%), decreased white blood cell count (45.5%), and liver impairment (45.5%). Grade 3 adverse events occurred in one (4.5%) patient.ConclusionRC48, particularly in combination regimens, demonstrates promising efficacy in advanced NSCLC with HER2 alterations. These findings underscore the need for further research to validate RC48’s application in clinical practice.

Abstract The laminar nature of microfluidic flows is most elegantly demonstrated via the confluence of two fluids forming two stable parallel flows within a single channel meeting at a highly stable interface. However, maintenance of laminar conditions can become complicated when there is a large viscosity contrast between the neighbouring flows leading to unique instability patterns along their interface. Here, we study the dynamics of high viscosity contrast confluent flows – specifically a core flow made of highly viscous glycerol confined by sheath flows made of water within a microfluidic flow focusing system. Our experiments indicate the formation of tapered core structures along the middle of the channel. Increasing the sheath flow rate shortens the tapered core, and importantly induces local instability patterns along the interface of core-sheath flows. The dynamics of such tapered core structures is governed by the intensity of instability patterns and the length of the core, according to which the core structure can experience stable, disturbed, broken or oscillated regimes. We have studied the dynamics of tapered core structures under these regimes. In particular, we have analysed the amplitude and frequency of core displacements during the broken core and oscillating core regimes, which have not been investigated before.

Water jacket systems are routinely used to control the temperature of Petri dish cell culture chambers. Despite their widespread use, the thermal characteristics of such systems have not been fully investigated. In this study, we conducted a comprehensive set of theoretical, numerical and experimental analyses to investigate the thermal characteristics of Petri dish chambers under stable and transient conditions. In particular, we investigated the temperature gradient along the radial axis of the Petri dish under stable conditions, and the transition period under transient conditions. Our studies indicate a radial temperature gradient of 3.3 °C along with a transition period of 27.5 min when increasing the sample temperature from 37 to 45 °C for a standard 35 mm diameter Petri dish. We characterized the temperature gradient and transition period under various operational, geometric, and environmental conditions. Under stable conditions, reducing the diameter of the Petri dish and incorporating a heater underneath the Petri dish can effectively reduce the temperature gradient across the sample. In comparison, under transient conditions, reducing the diameter of the Petri dish, reducing sample volume, and using glass Petri dish chambers can reduce the transition period.

A new genus and species of Schizopteridae, Cornonannus bui gen. et sp. nov. is described from Yunnan Province, China. The new genus is closest to Pachyplagia Gross, 1951, Ogeria, Distant 1913, and Kaimon Hill, 2004 in morphology, but it can be distinguished from these genera by the male having a frontal process, the absence of pronotal collar, the distinct venation of forewing, a tarsi formula of 3-3-3, and the middle area of abdominal tergites I to VII with small, round tubercles. Photographs of the male habitus, head, thorax, abdomen, appendages, and genitalic structures, as well as scanning electron micrographs of the male head, thorax, abdomen, and genitalic structures and drawings of male genitalia, are provided. Moreover, a key to all known Chinese schizopterid genera is presented.

Objectives: Association of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and kidney injury has been noted in previous studies. However, the mechanisms remain unknown. The present study aimed to explore the potential mechanisms of kidney injury in COVID-19. Methods: Demographic characteristics, underlying diseases, signs, symptoms, and laboratory data of 100 COVID-19 patients were collected and analyzed in this retrospective study. Patients were divided into three groups: mild, moderate, and severe to critical group. Kidney injury was evaluated by markers including estimated glomerular filtration rate (eGFR), serum creatinine, blood urea nitrogen, and cystatin C. Results: A total of 100 patients with 12 mild, 63 moderate, and 25 severe to critical COVID-19 were included in this study. The kidney injury markers including eGFR, serum creatinine, blood urea nitrogen, and cystatin C all worsened significantly with an increase in disease severity. The correlation test showed that cytokines IL-2R, IL-6, IL-8, and tumor necrosis factor (TNF)-α were statistically correlated with eGFR and cystatin C. In multivariate analysis, log IL-6 (β = −0.331, p = .001 for eGFR and β = 0.405, p < .001 for cystatin C) and log TNF-α (β = −0.316, p = .001 for eGFR and β = 0.534, p < .001 for cystatin C) were found to be the major independent predictors of kidney injury. Conclusion: Serum IL-6 and TNF-α levels were the major independent predictors of kidney injury in COVID-19.

Objectives Occipitocervical fusion (OCF) is an effective treatment for instability of occipitocervical junction (OCJ). The occipital condyle screw serves as a novel surgical technique for occipitocervical fixation. However, the intraoperative procedures for the occipital condyle screw technique have relied on surgeons’ experience, so the pool of surgeons who are able to perform this surgery safely is limited. The present study aims to evaluate the feasibility and safety of the occipital condyle screw technique using human cadavers and to provide image anatomy for clinical application basis. Methods The scientific study comprised 10 fresh‐frozen cadaveric specimens from the anatomy department of Qingdao University. Placement of the occipital condyle screws (3.5 mm diameter and 20.0 mm length) was performed in the 10 fresh‐frozen cadaveric specimens with intact occipitocervical junctions, respectively. Occipitocervical CT was performed for all specimens and the DICOM data was obtained. Occipitocervical CT three‐dimensional (3D) reconstruction was performed for the cadavers. Morphometric analysis was performed on the bilateral occipitocervical junction of 10 cadaveric specimens based on the 3D reconstruction CT images. Detailed morphometric measurements of the 20 occipital condyles screws were conducted including the average length of the screw trajectory, inside and upper tilting angles of screws, distance to the hypoglossal canal, and to the medial wall of occipital condyle. Results Placement of the occipital condyle screws into the 20 occipital condyles of the 10 cadaveric specimens was performed successfully and the trajectory of implantation was satisfactory according to 3D CT reconstruction images, respectively. There was no obvious injury to the spinal cord, nerve root, and vertebral artery. The length of the bilateral screw trajectory was, respectively, 20.96 ± 0.91 mm (left) and 20.59 ± 0.77 mm (right) (t = 1.306, P > 0.05). The upper tilting angle of bilateral screws was, respectively, 11.24° ± 0.74° (left) and 11.11° ± 0.64° (right) (t = 0.681, P > 0.05). The inside tilting angle of bilateral screws was, respectively, 31.00° ± 1.32° (left) and 30.85° ± 1.27° (right) (t = 0.307, P > 0.05). The screw's distance to the bilateral hypoglossal canal was, respectively, 4.84 ± 0.54 mm (left) and 4.70 ± 0.54 mm (right) (t = 0.685, P > 0.05). The screw's distance to the medial wall of the bilateral occipital condyle was, respectively, 5.13 ± 0.77 mm (left) and 5.04 ± 0.71 mm (right) (t = 0.384, P > 0.05). Conclusion The occipital condyle screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction with meticulous preoperative planning of the screw entry point and direction based on individual differences. Morphometric trajectory analysis is also an effective way to evaluate the surgical procedure.

Background: Automated peritoneal dialysis (APD) can cater to individual needs, provide treatment while asleep, take into account the adequacy of dialysis, and improve the quality of life. Currently, independent research and development of APD machines made in China are more conducive to patients. A randomized, multicenter, crossover study was conducted by comparing an APD machine made in China with an imported machine. The safety, effectiveness, and manipulability of the two machines were compared. Methods: Two hundred and sixty patients who underwent peritoneal dialysis (PD) on a regular basis in 18 centers between August 2015 and February 2016 were included. The inclusion criteria include age ≥18 years and PD ≥30 days. The exclusion criteria were as follows: hemodialysis; exit site or tunnel infection; and peritonitis ≤30 days. The patients were randomly divided into Group A, who were first treated with a FM machine made in China, then changed to an imported machine; and Group B, who were treated using the reverse sequence. APD treatment was performed with 10 L/10 h and 5 cycles of exchange. After 72 h, the daily peritoneal Kt/V, the accuracy of the injection rate, accuracy of the injection temperature, safety, and manipulability of the machine were assessed. Noninferiority test was conducted between the two groups. Results: The daily peritoneal Kt/V in the APD machine made in China and the imported APD machine were 0.17 (0.14, 0.25) and 0.16 (0.13, 0.23), respectively. There was no significant difference between the groups (Z = 0.15, P = 0.703). The lower limit of the daily Kt/V difference between the two groups was 0.0069, which was greater than the noninferiority value of −0.07 in this study. The accuracy of the injection rate and injection temperature was 89.7% and 91.5%, respectively, in the domestic APD machine, which were both slightly better than the accuracy rates of 84.0% and 86.8% in the imported APD machine (89.7% vs. 84.0%, P = 0.2466; 91.5% vs. 86.8%, P = 0.0954). Therefore, the APD machine made in China was not inferior to the imported APD machine. The fuselage of the imported APD machine was space-saving, while the APD machine made in China was superior with respect to body mobility, man-machine dialog operation, alarm control, and patient information recognition. Conclusions: The FM machine made in China was not inferior to the imported APD machine. In addition, the FM machine made in China had better operability. Trial Registration: Clinicaltrials.gov, NCT02525497;.

The joint roughness coefficient (JRC) is an important factor affecting the shear properties of rock joints, and its accurate estimation is a challenging task in rock engineering. Existing JRC evaluation approaches such as the empirical comparison method and the statistical parameter method have some unresolved defects. In this study, a new method is proposed for JRC estimation to overcome the deficiencies of existing approaches based on back calculation of shear strength. First, the 10 standard roughness joints are established in numerical rock samples generated by the bonded particle method (BPM). Secondly, the microscopic parameters of the intact rock and joints are calibrated, and a series of direct shear tests of joint samples are carried out under different normal stresses. Finally, the empirical relationships between shear strength and JRC are proposed under high correlation conditions. The results show that the modified smooth joint model (MSJM) is proved to better simulate the mechanical properties of rough joints than the smooth joint model (SJM). When the shear strength of target joint is substituted in the corresponding relationship, the JRC of joint along the shear direction can be conveniently obtained. In addition, the JRC values of 10 standard roughness joint profiles under shear direction of from right to left (FRTL) are obtained. By estimating the JRC of 9 target joints in the literature, it can be seen that the new method proposed in this paper can well reflect the directionality of roughness and it is convenient to apply.

Objective(s):Spinal cord injury (SCI) often causes serious and irreversible neurological deficit leading to disability or impairment of normal physical activity. Atomoxetine, a selective norepinephrine transporter (NET) inhibitor has gained much attention in the field of the neurodevelopmental disorder, but its effect on SCI has not been evaluated. The present study has been undertaken to investigate the neuroprotective effects of atomoxetine. Materials and Methods: Administration of atomoxetine 20 mg/kg IP was compared with methylprednisolone (MP) 30 mg/kg IP in traumatic spinal cord injured Wistar rats. Tissue samples were evaluated for apoptosis, inflammation, and oxidative stress, along with histopathological examination and neurological evaluation. Results: There was no significant difference in the caspase-3 activity between the control and the sham groups or between the MP and the atomoxetine groups (P=0.811). The administration of atomoxetine significantly reduced tissue tumour necrosis factor alpha (TNF-α), and nitric oxide (NO) levels compared to the trauma group (P

Background: Spinal degenerative diseases are a major health problem and social burden worldwide. Intervertebral disc degeneration (IDD) is the pathological basis of spinal degenerative diseases and is characterized by loss of nucleus pulposus cells due to excessive apoptosis caused by various factors. MicroRNAs (miRNAs) have been reported to be functionally involved in the control of apoptosis. Methods: computational analysis and luciferase assay were used to identify the target of miR-125a, and cell culture, transfection were used to confirm such relationship. Sequencing was used to determine the genotype of each participant. Results: We confirmed the previous report that the presence of the minor allele (T) of rs12976445 polymorphism significantly downregulated the expression level of miR-125a in nucleus pulposus cells, leading to less efficient inhibition of its target gene. We also validated TP53INP1 as a target of miR-125a in nucleus pulposus cells using a dual luciferase reporter system, and the transfection of miR-125a significantly reduced the expression of TP53INP1. The expression level of TP53INP1 was significantly lower in nucleus pulposus cells genotyped as CT or TT than in those genotyped as CC, and the apoptosis rate was consistently lower in the CC group than in the nucleus pulposus cells collected from individuals carrying at least one minor allele of rs12976445 polymorphism. To study the association between rs12976445 polymorphism and the risk of IDD, we enrolled 242 patients diagnosed with IDD and 278 normal controls, and significant differences were noted regarding the genotype distribution of rs12976445 between the IDD and the control groups (OR = 2.69, 95% C.I. = 1.88-3.83, p Conclusion: The present study indicated that miR-125a is a promising potential target for patients with IDD in clinical practice.