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Objective To investigate the clinical efficacy and safety of fruquintinib combined with sintilimab in the treatment of advanced microsatellite stable (MSS) colorectal cancer. Methods A retrospective study of 44 patients with MSS colorectal cancer treated with fruquintinib and sintilimab was conducted.The patients were divided into the fruquintinib alone (n=22) and fruquintinib combined with sintilimab (n=22) groups.The treatment regimen was as follows: The patients in the fruquintinib alone group consumed oral fruquintinib capsules at 5 mg/d once for three consecutive weeks with a one week stop in 28 day cycles.The patients in the fruquintinib combined sintilimab group were injected intravenously with sintilimab (200 mg) once per three weeks, and fruquintinib was used in the same manner as the fruquintinib alone group. Results The objective response rate (ORR) of the fruquintinib alone group was 9.09%, the disease control rate (DCR) of the fruquintinib alone group was 45.45%.The ORR of the fruquintinib combined with sintilimab group was 18.18%, and the DCR was 63.64%.The median PFS of the fruquintinib alone and fruquintinib combined with sintilimab groups were 4.4 months (IQR: 2.1-8.2) and 6.7 months (IQR: 3.9-12.6), respectively (χ2=4.372, P=0.037).Most of the adverse reactions during the treatment of the two groups were grades 1-2.In addition, no significant difference in the incidence of adverse reactions was found between two groups (P > 0.05). Conclusion Compared with fruquintinib alone, fruquintinib combined with sintilimab in the treatment of patients with MSS colorectal cancer after the failure of standard treatment has better clinical efficacy, and adverse drug reactions can be controlled.

Internal carbon pricing has the potential to positively influence enterprises’ carbon emissions. However, the strategies for implementing internal carbon pricing for enterprises and internal organizations remain unclear. In this study, employing a differential game research methodology, we design three implementation strategies for internal carbon pricing from a dynamic time perspective. Through comparative research and numerical analysis of these three different strategies’ effects on the changes in enterprise carbon emission reduction and goodwill, we find that for both enterprises’ carbon emission reduction and goodwill, Model C (implementing secondary investment for internal carbon fee collection) is optimal when the proportion of internal organizational revenue allocation is high and the proportion coefficient of internal carbon fee collection is low. When the proportion coefficient of internal carbon fee collection meets certain conditions, it makes the total profit of system under model C (implementing secondary investment for internal carbon fee collection) larger than the other two strategies. Due to short-sighted behavior, both enterprises’ profits and carbon emissions gradually decrease, leading to the internal carbon prices of enterprises under the three strategies will approach a stable value.

Cold rolling and heat treatment experiments of GH4169 alloy with different deformation were carried out. Effect of different cold rolling deformation and heat treatment state on microstructure and hardness of plate was analyzed. Cold rolling experimental results show that dislocation density is increased, dislocations are cross slipped, deformation texture are enhanced, twins boundaries are decreased and hardness is improved with the increasing of deformation. Different heat treatment experimental results show that when the cold rolling deformation within 0%-20%, after 980 ℃×10 min solution treatment, the recrystallization is incepted, grains are refined, deformed grains and dislocation are remained in the plate. When the deformation within 0%-20%, deformed grains are remained and recrystallized grain size is refined with the increasing of deformation, thus the hardness of solution treated plate is increased with the increasing of deformation. The recrystallization finished and work hardening is eliminated,thus the hardness of solution treated plate decline to undeformed level and remains unchanged when the deformation larger than 25%. The γ' and γ'' phases are precipitated in the plate after aging heat treatment, and the hardness of the plate is significantly higher than that of the cold rolled and solid solution treatment states, and the hardness is basically not affected by the deformation amount of cold rolling. The threshold value of cold rolling deformation for recrystallization inception of GH4169 alloy is within 5%-10% during 980 ℃ solution treatment. And the cold rolling deformation threshold value of complete recrystallization is about 25%. According to actual production condition, the optimal cold rolling deformation is larger than 25%, and the matched solution treatment is 980 ℃×10 min.

ObjectiveTo investigate and analyze the epidemiological characteristics of a wild mushroom poisoning event in Qinhuangdao City, identify the species of poisonous mushroom, summarize the experience of investigation and treatment, and put forward prevention and control measures, and provide reference for the treatment and prevention of wild mushroom poisoning patients.MethodsThe poisoning events were analyzed by using the method of epidemiological investigation, morphological identification and mushroom toxin detection.ResultsFour villagers in Qinhuangdao city had nausea, abdominal pain, diarrhea, sweating and shivering after eating wild mushrooms. Patients were treated with vomiting, gastric lavage, atropine and other symptomatic treatment in the hospital, and the prognosis of the patients was good. After morphological identification and toxin detection, it was determined that food poisoning caused by mushroom of inocybe.ConclusionThis is the first reported poisoning event caused by mushroom of inocybe in Hebei Province. The reason of poisoning was misguided by the Internet and poor self-awareness of food safety. Therefore, publicity and education should be strengthened, enhancing the awareness to prevent the poisoning of wild mushroom.

Objective To provide a clinical reference by evaluating the precision of virtual surgical planning in two-jaw orthognathic surgery.Methods Thirty consecutive patients who required two-jaw orthognathic surgery were included. A composite skull model was reconstructed using data from spiral computed tomography scan and surface scanning of the dental arch. LeFort I osteotomy of the maxilla and bilateral sagittal split ramus osteotomy of the mandible were simulated using Dolphin Imaging 11.7 Premium. Genioplasty was performed if indicated. Virtual plan was then transferred to operation room using 3D-printed surgical templates. Frankfort horizontal plane (FHP), midfacial plane (perpendicular to the FHP through the nasion), and coronal plane (perpendicular to the FHP through the sella point) were the selected three symmetry planes.Midpoint of the contact of the maxillary and mandibular central incisors (UI, LI), and the mesio-buccal cusp of the first maxillary and mandibular molars (U6-R,U6-L, L6-R, L6-L) were the six chosen volumetric landmarks. To calculate the linear difference and overall mean linear difference (mean difference of the distance between UI, LI, U6-R, U6-L, L6-R, L6-L to FHP, midfacial and coronal plane) between simulated and postoperative models, the distance between selected landmarks and symmetry planes was measured. To calculate the angular difference and overall mean angular difference, values of the angles constructed by the occlusal, palatal, and mandibular plane to FHP and midfacial plane respectively were determined on simulated and postoperative models.Results The virtual surgical planning was successfully transferred to actual surgery with the help of 3D-printed surgical templates. All patients were satisfied with the postoperative facial profile and occlusion. The overall mean linear difference was 0.81 mm (0.71 mm for maxilla and 0.91 mm for mandible); and the overall mean angular difference was 0.95° (the mean angular difference relative to FHP was 1.10°, and that relative to midfacial plane was 0.83°).Conclusion Virtual surgical planning facilitated the diagnosis, treatment planning, and precise bony segments repositioning in two-jaw orthognathic surgery.

The circuit techniques that suppress pop-click noise and reduce saturation distortion are presented for class D amplifier in mobile application. Pop-click noise level is effectively suppressed by detecting power voltage, controlling preamplifier and driver circuits of power stage in sequence, and providing discharge path between amplifier output and ground. Meanwhile, in class D power amplifier with feedback loop structure, the integrator is easy to saturate when a large amplitude signal is fed into the input terminal of the amplifier. Consequently, the saturation distortion is generated in amplifier output when the pulse width modulator fails to modulate input signal due to integrator saturation. The compensation technique in the pulse width modulator output can effectively reduce the saturation distortion, and also eliminate the risk of the transistor switch thermal damage due to power MOSFET still on state. The proposed class D amplifier with the above features was fabricated with 0.35 μm CMOS process. Pop-click noise level of 1.5 mV，THD+N of 0.025% can be achieved in 3.6 V power supply.

The key of the degenerate state recognition of roller bearing is feature extraction and pattern recognition. Local characteristic-scale decomposition（ LCD） is a new time-frequency analysis method,which is very suitably applied to the feature extraction of roller bearing vibration signal. Since variable predictive model based class discriminate（ VPMCD） is a pattern recognition method in which the relationship between the feature values is adopted,it can be applied to the he degenerate state recognition of roller bearing. In this paper,LCD,VPMCD and Gaussain mixture model（ GMM） are combined. Furthermore,the degenerate state recognition method of rolling bearings based on LCD and GMM-VPMCD hybrid model is proposed. Firstly,the whole life data of rolling bearing is decomposed by LCD method and the feature values of the components are extracted; then the feature values are clustered in time domain by using GMM and the whole life data is divided into some degenerate states in time domain; finally,the VPMCD model is constructed and applied to the degenerate state recognition of roller bearing. The experiment results show that the GMM-VPMCD hybrid model based on LCD can be effectively applied to the degenerate state recognition of rolling bearing.