OBJECTIVE To systematically evaluate the efficacy and safety of Insulin degludec and liraglutide injection （IDegLira） and Insulin glargine and lixisenatide injection（iGlarLixi） in the treatment of type 2 diabetes mellitus（T2DM）， and provide an evidence-based basis for the clinical treatment of T2DM. METHODS Computerized searches of PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP were conducted with a time frame from the inception to August 2024. Randomized controlled trials（RCTs） were rigorously screened according to inclusion and exclusion criteria， from which information was extracted and included studies were evaluated for risk of bias. Network meta-analysis was performed using Stata 14.0 software. RESULTS A total of 15 RCTs， including 9 513 patients， were included， involving four treatment regimens： IDegLira， iGlarLixi， insulin degludec（IDeg）， and insulin glargine（iGlar）. The differences between IDegLira and iGlarLixi were not statistically significant（P＞0.05） for the outcome indexes of glycosylated hemoglobin（HbA1c）， fasting blood glucose， body weight， and the incidence of adverse events（P＞0.05）； for the outcome index of the incidence of hypoglycemic events， IDegLira was significantly superior to iGlarLixi [OR＝0.41，95%CI（0.18，0.91），P＜0.05]. Surface under the cumulative ranking curve（SUCRA） results showed that iGlarLixi（84.5%）＞IDegLira（81.7%） in lowering HbA1c； IDegLira（71.3%）＞iGlarLixi（20.0%） in lowering fasting blood glucose； IDegLira（90.7%）＞iGlarLixi（61.8%） in lowering body weight； IDegLira（95.5%）＞iGlarLixi（9.7%） in reducing the incidence of hypoglycemic events； and IDegLira（27.1%）＞iGlarLixi（14.5%） in reducing the incidence of adverse events. CONCLUSIONS iGlarLixi has better therapeutic efficacy in reducing HbA1c； IDegLira has better therapeutic efficacy in reducing fasting blood glucose and body weight. IDegLira has the lowest risk of hypoglycemia.

OBJECTIVE From the perspective of China’s healthcare system， to evaluate the cost-effectiveness of amivantamab combined with chemotherapy versus chemotherapy alone for patients with EGFR-mutated advanced non-small cell lung cancer （NSCLC） who experience disease progression during or after treatment with osimertinib monotherapy. METHODS The Markov model was established according to MARIPOSA-2 clinical trial. The simulation time limit was 10 years and the cycle period lasted for 21 days. The incremental cost-effectiveness ratio（ICER） of amivantamab combined with chemotherapy versus chemotherapy alone for the treatment of EGFR-mutated advanced NSCLC was calculated， and then compared with the willingness-to-pay（WTP） threshold set in this study[3 times the per capita gross domestic product（GDP） of China in 2023， which was 268 200 yuan per quality-adjusted life year（QALY）]， in order to assess its cost-effectiveness. Single-factor sensitivity analysis and probability sensitivity analysis were performed to evaluate the stability of the model； scenario analysis was carried out to determine the potential price of amivantamab at which the regimen became cost-effective. RESULTS Compared with chemotherapy alone， the cost of amivantamab combined with chemotherapy was higher （1 248 411.60 yuan vs. 89 023.39 yuan）， but at the same time， there were also more benefits of survival （0.756 QALY vs. 0.584 QALY）， ICER was 6 757 285.38 yuan/QALY. ICER was most affected by the utility of progression-free survival and the price of amivantamab. The price of amivantamab decreased to 310.3 yuan per 350 mg， and the combination therapy became cost-effective， compared with chemotherapy alone. CONCLUSIONS From the perspective of Chinese health system， when the WTP threshold is set at three times the per capita GDP of the Chinese population in 2023， amivantamab combined with chemotherapy is not cost-effective for EGFR-mutated advanced NSCLC； the patients’ affordability can be improved when the price of amivantamab experiences a significant decrease.

BACKGROUND:Bone tissue defects are one of the most common diseases in orthopedics,and the current treatments for this disease are inadequate.The development of tissue engineering brings new hope for bone defect repair:by regulating the release of bioactive substances and the process of vascularization and neurogenesis at the defect site,it can effectively improve the microenvironment of bone tissue and promote osseointegration,which is the most promising research idea for large-size bone defect repair. OBJECTIVE:To explore the research progress of regulating bone microenvironment changes in bone defect repair in recent years from the effects of bioactive substances,vascularization and neurotization on three aspects of bone microenvironment changes,and to provide new ideas and strategies for the treatment of large-size bone defects. METHODS:The search terms"bone tissue engineering,angiogenesis,neurotization,cytokines,bone morphogenetic protein,vascular endothelial growth factor,neuropeptides,bone microenvironment"in Chinese and English were used to search for articles on the influence of changes in the bone microenvironment and their application in bone tissue engineering published from January 1,2001 to December 31,2022 on CNKI,WanFang,Web of Science,Science Direct,and PubMed.Finally,109 articles were included for review. RESULTS AND CONCLUSION:(1)The bone microenvironment is essential for the induction of bone tissue stem cell growth and differentiation,and mainly consists of the extracellular matrix of the bone tissue seeds and the biochemical factors required for intercellular interactions,the local blood circulation network and the surrounding nerve tissue.(2)Bone defect repair is a continuous process divided into multiple phases that overlap and are mediated by multiple cytokines,and the same cytokine can have mutually synergistic or antagonistic effects in one or more healing phases.(3)Neovascular regeneration is key to initiating bone repair,as neovascularisation not only provides essential nutrients,osteoblasts and growth factors for bone repair,but is also a gateway for repair cells to enter the injury zone.(4)In addition to regulating the type,dose and timeliness of vascular-inducing factor release to achieve blood transport reconstruction.The study of differential release delivery systems of multiple factors and the application of gene transfer technology will be the future research direction to solve large bone defects.(5)Neuropeptides can bind to relevant receptors and act on specific signaling pathways to guide vascular growth and influence bone healing,bone regeneration and the balance between osteogenesis and osteolysis through a variety of pathways.(6)In the establishment of neuralized tissue-engineered bone,the role of changes in the bone tissue microenvironment and neuromodulation is bidirectional.Cytokines in the bone matrix can participate in neuronal signaling pathways through the blood-nerve barrier.Neuropeptides secreted by glial cells act on the bone microenvironment,affecting bone healing,bone regeneration and the balance between osteogenesis and osteolysis.(7)There are still many questions regarding the regulation of the bone microenvironment by bioactive substances and the processes of vascularization and neurogenesis,such as the rapid diffusion and degradation of cytokines in the body and their loss of activity,the temporal and spatial distribution of angiogenesis-related growth factors,and the establishment of neurogenesis through the body's feedback regulatory mechanism,which need to be improved by subsequent studies.

Objective To investigate the correlation between somatosensory evoked potentials(SEP)of upper limbs,and sensory and motor functions in stroke patients in different stages. Methods From June,2021 to October,2023,177 stroke patients in Shijiazhuang People's Hospital were diveded into acute stage group(within 14 days,n=25),early recovery group(14 days to one month,n=110)and middle to late recovery group(one to six months,n=42)according to the duration of the disease.General information of the patients was recorded;SEP examination was performed,and N20 lantency and amplitude were recorded.Monofilament touch and two-point discrimination sensation of the patient's hands were tested using the monofila-ment and two-point discrimination tools,respectively;and motor function was assessed with Fugl-Meyer Assess-ment-Upper Extremities(FMA-UE).The correlation between SEP,and the sensory and motor scores in each group was analyzed. Results There was no significant difference in the monofilament tactile and two-point discrimination scores among the three groups(P>0.05).SEP was not correlated with sensory and motor functions in the acute stage group(P>0.05);in the early recovery group,N20 latency was negatively correlated with monofilament tactile sensation(r=-0.267,P=0.005)and positively correlated with two-point discrimination sensation(r=0.220,P=0.021),and N20 amplitude was positively correlated with monofilament tactile sensation(r=0.328,P<0.001)and FMA-UE score(r=0.418,P<0.001),and negatively correlated with two-point discrimination(r=-0.405,P<0.001);in the middle to late recovery group,the N20 latency was negatively correlated with FMA-UE score(r=-0.313,P=0.044),and N20 amplitude was positively correlated with monofilament tactile sensation(r=0.598,P<0.001)and FMA-UE score(r=0.393,P=0.010),and negatively correlated with two-point discrimination(r=-0.591,P<0.001).Multiple linear regression analyses showed that the score of monofilament tactile sensa-tion was negatively correlated with N20 latency(β=-0.510,P=0.046),and the FMA-UE score was positively correlated with N20 amplitude(β=0.313,P=0.026)in the middle to late recovery group;in the early recovery group,the two-point discriminative sensation score was negatively correlated with N20 amplitude(β=-0.270,P=0.039). Conclusion The correlation between SEP and sensory and motor functions becomes more significant with the prolonga-tion of disease.

Objective:To discuss the inhibitory effect of Schisandrin B on the proliferation of pancreatic cancer Pan02 cells,and to clarify the mechanism.Methods:CCK-8 method was used to detect the proliferation rates of the Pan02 cells after treated with different concentrations(0,0.78,1.56,3.12,6.25,12.50,and 25.00 mg·L-1)of Schisandrin B to select the optimal concentration and treatment time of Schisandrin B.The mouse pancreatic cancer Pan02 cells were divided into control group(0 mg·L-1 Schisandrin B),2.5 mg·L-1 Schisandrin B group,5.0 mg·L-1 Schisandrin B group,and 10.0 mg·L-1 Schisandrin B group.The morpholoy of Pan02 cells invarious groups was observed with light microscope;5-ethynyl-2'-deoxyuridine(EdU)staining assay was used to detect the positive expression rates of the Pan02 cells in various groups;flow cytometry was used to detect the percentages of the Pan02 cells at different cell cycles and the apoptotic rates of the cells in various groups;Western blotting method was used to detect the expression levels of cell cycle and apoptosis-related proteins in the cells in various groups.Results:The CCK-8 method results showed that after treated with Schisandrin B for 48 and 72 h,compared with 0 mg·L-1 Schisandrin B,the proliferation rates of the Pan02 cells after treated with different concentrations of Schisandrin B were decreased(P<0.01),especially at 72 h.0.25,5.0,and 10.0 mg·L-1 Schisandrin B were selected to treat the Pan02 cells,and 72 h was the treatment time.In control group,the Pan02 cells had a spindle shape,with good condition,and grew closely adhered to the wall with normal organelles and cytoplasm,in 2.5 and 5.0 mg·L-1 Schisandrin B groups,the cell volume was decreased,the intercellular adhesion was disappeared,and the cell membrane was intact but more permeable;the cytoplasm shrank and vacuolar structures appeared inside the cells,with some fragmented and floating on the surface of the solution;in 10.0 mg·L-1 Schisandrin B group,the Pan02 cells exhibited notable apoptotic bodies,indicating an apoptotic state.The EdU staining results showed that compared with control group,the rates of EdU positive cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.01).The flow cytometry results showed that compared with control group,the percentages of the cells at S phase in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01),while the percentages of the cells at G2/M phase were significantly decreased(P<0.01),and the percentages of the cells at G0/G1 phase in 5.0 amd 1.0 mg·L-1 Schisandrin groups were decreased(P<0.01);compared with control group,the apoptotic rates of the cells in 2.5,5.0,and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).The Western blotting results showed that compared with control group,the expression levels of p27,B-cell lymphoma 2(Bcl-2)associated X protein(Bax),cleaved cysteine aspartic acid protease-3(cleaved Caspase-3),and cleaved poly adenosine diphosphate(ADP)ribose polymerase(cleaved PARP)proteins in the cells in 2.5 mg·L-1 Schisandrin B group were significantly increased(P<0.05 or P<0.01),the expression levels of cyclin A2,cyclin E2,and Bcl-2 proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly decreased(P<0.05 or P<0.01),while the expression levels of p27,Bax,cleaved Caspase-3,and cleaved PARP proteins in the cells in 5.0 and 10.0 mg·L-1 Schisandrin B groups were significantly increased(P<0.01).Conclusion:Schisandrin B has an inhibitory effect on proliferation of the pancreatic cancer Pan02 cells,and its mechanism may be related to the activation of the cysteine aspartic acid protease-3(Caspase-3)pathway to induce the apoptosis and activating p27 protein to induce the arrest of cell cycle at S phase.

OBJECTIVE: To carry out genetic diagnosis for a fetus. METHODS: Chromosome G-banding and chromosomal microarray analysis (CMA) were carried out for a fetus with abnormal morphology of lateral cerebral fissure. RESULTS: The karyotype of the fetus was normal, but CMA showed that it has carried a 1.4 Mb deletion at 17p13.3 region, which suggested a diagnosis of Miller-Dieker syndrome (MDS). CONCLUSION Familiarity with clinical features and proper selection of genetic testing method are crucial for the diagnosis of MDS. Attention should be paid to microdeletions and microduplications which can be missed by conventional chromosomal karyotyping.
Chromosome Banding ; Chromosome Deletion ; Chromosomes, Human, Pair 17 ; Classical Lissencephalies and Subcortical Band Heterotopias/genetics* ; Female ; Fetus ; Humans ; Karyotyping ; Pregnancy ; Prenatal Diagnosis

Objective:To investigate the application value of third-generation dual-source CT(3-G DSCT) low-dose scan mode combined with iterative reconstruction technology in the screening of COVID-19 and to evaluate the radiation dose.Methods:One hundred and twenty patients suspected of COVID-19 from December 2019 to February 2020 were retrospectively analysed and randomly divided into two groups (test group and conventional group, 60 patients in each). The parameters for test group included 3-G DSCT, Turbo Flash scan mode, CARE kV, with reference 90 kV, pitch 2.0, and ADMIRE algorithm, while those parameters for conventional group included the 128-slice CT, conventional spiral scan mode, 120 kV, pitch 1.2, and FBP algorithm. The CT values of aorta, spinal posterior muscle, and subcutaneous fat, the aortic noise, signal-to-noise ratio (SNR), and contrast noise ratio (CNR) were compared to evaluate the image quality between two groups. Two experienced doctors scored the image quality using a double-blind method, and compared the CT dose index volume (CTDI vol), dose-length product (DLP), and effective dose ( E) of the two groups. Results:The CT value of the aorta and spinal posterior muscle and the aortic SNR in the test group were (45.38±4.77), (53.41±8.44) HU, and 2.82±0.59, and significantly higher than those in the conventional group [(39.68±6.26), (42.66±6.32) HU, 2.58±0.61, t=5.608, 7.897, 2.162, P<0.05]. The aortic noise, CNR and subjective scores between the two groups had no significant difference( P>0.05). The CTDI vol, DLP, and E in the test group were (3.09±1.02) mGy, (107.57±32.81) mGy·cm, (1.51±0.46) mSv, significantly lower than those in the conventional group [(7.00±1.80) mGy, (261.65±73.93) mGy·cm, (3.66±1.03) mSv; t=-14.680, -14.756, -14.756, P<0.05]. Conclusions:In the screening of COVID-19, using low-dose scanning mode of 3-G DSCT combined with iterative reconstruction technology would provide diagnostic quality images and meanwhile effectively reduce the radiation dose and improve the SNR of the image.

Objective To study the effect of Pinus yunnanensis on acute alcoholic liver injury in rats and explore its mechanism. Methods A model of acute alcoholic liver injury in mice was prepared by alcohol. The mice were randomly divided into normal control group, model group, positive control group, Pinus yunnanensis low-, medium-and high-dose groups. Mice in the medicine group were given the corresponding medicine by gavage once a day for 7 days. After the last three hours of intragastric administration, the liver and spleen index, ALT, AST and GSH in serum, SOD, MDA and NO in liver homogenates were measured. Histopathological changes of liver were observed by HE staining. Results Compared with model group, Pinecone of Pinus unnanensis high-, medium- and low-dose groups could significantly reduce the liver index in mice (P<0.01), and high dose groups could significantly reduce the number of spleen (P<0.01); The contents of AST in the medium- and high-dose groups significantly decreased (P<0.01) and the GSH activity significantly increased (P<0.05, P<0.01). There was no significant difference in serum ALT level, SOD activity, GSH activity and NO content in the liver tissues of Pinus yunnanensis groups (P>0.05). HE staining results showed that, the damage of liver tissue in mice of Pinus yunnanensis was significantly improved compared with the model group. Conclusion Pinus yunnanensis has protective effects on acute alcoholic liver injury in mice.

Objective To investigate the relationship between occult pancreaticobiliary reflux (OPR) and biliary diseases.Methods Forty-four patients with primary biliary diseases was enrolled,and serum amylase level was determined,and the bile in common bile duct (CBD) was collected to measure the amylase level,then the △ amylase was calculated,which equals bile amylase level minus serum amylase level.OPR was confirmed if bile amylase level was higher than serum amylase level,otherwise it would be defined as the control group.Results Among the 44 patients with primary biliary diseases,the incidence of OPR was 72.7％ (n =32).The bile and serum amylase activity of patients with OPR were (1 513 ± 2 725),(44 ± 21)U/L;and they were (18 ± 14) and (38 ± 17) U/L in the control group.The bile amylase level in OPR group was significantly higher than that in the control group,and the difference was statistically significant (P ＜ 0.05),while there was no significant difference in serum amylase activity between the two groups.The incidence of OPR in patients with CBD stones was 100％,and the bile amylase activity was (1 048 ± 1 317) IU/L,and the △ bile amylase activity was (996 ± 1 322) U/L;the incidence of OPR in patients with choledocholithiasis and cholecystolithiasis was 75％,and the bile amylase activity was (2 457 ± 3 312),the △ amylase activity was (2 412 ± 3 320)IU/L;and the corresponding values in patients with gallbladder stones were 80％,(95 ± 82),(57 ± 76)IU/L;and the corresponding values in patients with bile duct cancer were 50％,(73 ± 51),(40 ± 37)U/L.Conclusions The occurrence of OPR is closely related to CBD stones only,CBD stones and gallbladder stones,and it may be one of the main pathogenic factors of bile duct stones.