Objective To investigate the changes of coagulation,fibrinolysis and platelet indexes in ovarian cancer patients before and after neoadjuvant chemotherapy,and to analyze the risk relationship between relevant indexes before treatment and the effect of neoadjuvant chemotherapy(NACT).Methods Patients with ovarian cancer admitted to Xi'an Fengcheng Hospital,from March 2020 to March 2023 were included as the ovarian cancer group,and female patients who underwent physical examination in the same period were selected as the control group according to a 2∶1 ratio.Prothrombin time(PT),thrombin time(TT),activated partial thromboplastin time(APTT),fibrinogen(FIB),platelet distribution width(PDW),platelet hematocrit(PCT),platelet(PLT)and mean platelet volume(MPV)were compared between the two groups.The changes of these indexes were compared before and after NACT,at different clinical stages and before and after NACT with different efficacy effects.Moreover,they were divided into effective and ineffective groups according to their treatment efficacy.Logistic regression was used to explore the relationship between the parameters and NACT efficacy;receiver operating characteristic curve was drawn to predict the value of NACT efficacy.Results A total of 144 patients were included,with 96 cases in the ovarian cancer group and 48 in the control group.The FIB,PLT and MPV of patients in the ovarian cancer group were higher than those in the control group(P<0.05).The PT,TT,APTT,FIB and PLT of ovarian cancer patients after NACT were lower than those before NACT(P<0.05).FIB and PLT of stage Ⅱ patients were lower than those of stage Ⅲ before and after NACT,and the PT,TT,APTT,FIB and PLT of the effective group were lower than those of the ineffective group before and after NACT,and the PT,TT,APTT,FIB and PLT of the two groups after NACT were lower than those before NACT(P<0.05).Multivariate Logistic regression analysis indicated that high PT,TT,APTT,FIB and PLT before NACT were independent risk factors for NACT ineffectiveness(P<0.05).The area under the curve of PT,TT,APTT,FIB and PLT before NACT to predict the effect of NACT were 0.713(sensitivity of 80.95%,specificity of 69.33%),0.756(sensitivity of 71.43%,specificity of 82.67%)and 0.787(sensitivity of 76.19%,specificity of 70.67%),0.727(sensitivity of 71.43%,specificity of 84.00%),0.794(sensitivity of 80.95%,specificity of 76.00%),respectively.Conclusion Changes in coagulation and fibrinolytic function and platelet parameters in ovarian cancer patients after NACT are associated with clinical stages and NACT effect.High levels of PT,TT,APTT,FIB and PLT before NACT are important reasons affecting NACT effect.Constructing the risk prediction model of NACT efficacy in ovarian cancer patients based on the above five parameters can provide a reference for clinical practice.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

Objective To systematically study the efficacy and safety of KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated. Methods Computer searches from PubMed, The Cochrane Library, Web of Science, Embase, CNKI, and CBM databases were conducted to collect clinical studies on KRAS^G12C inhibitors in advanced solid tumors with KRAS^G12C-mutated, with a search time from inception to October 12, 2022. Then, two investigators independently screened the literature, extracted information, assessed the risk of bias in included studies, and performed meta-analyses using RevMan 5.4 software. Results There were four publications included, all of which were single-arm clinical studies. The KRAS^G12C inhibitors that completed clinical phase Ⅰ and Ⅱ trials were sotorasib and adagrasib, with two publications each. A total of 388 and 394 patients were included in the efficacy evaluation and safety evaluation, respectively. Resultsof the Meta-analysis showed that the patients had objective response rate, overall disease control, and disease stabilization rates of 35%, 82%, and 45%, respectively. In addition, the rate of serious adverse events, general adverse events, and all adverse events in patients was 2%, 28%, and 79%, respectively. Moreover, the rate of partial remission of disease in NSCLC patients was 38%. Conclusion The KRAS^G12C inhibitors sotorasib and adagrasib exhibited good efficacy and high safety in advanced solid tumors.

Objective To investigate the biological role of LINC01614 in non-small cell lung cancer A549 cells and its drug resistance-related mechanism. Methods The CRISPR/Cas9 technology was used to construct the A549 cell model with knockdown of LINC01614. Transcriptome sequencing was performed on A549 cells knocked down with LINC01614. We validated the transcriptomic differential genes MCAM and ABCC3 at the gene level and MCAM at the protein level, detected the IC₅₀ changes of A549 cells after knockdown of LINC01614 under the effect of different concentrations of cisplatin, and detected the effect of knockdown of LINC01614 on the migration ability of A549 cells. Results Of the 2 713 DEGs after knockdown of LINC01614, a total of 1 626 genes were up-regulated and 1, 087 genes were down-regulated. GO analysis showed that DEGs were associated with intracellular signaling, cell adhesion, and so on. Meanwhile, the KEGG analysis showed that DEGs were associated with the Wnt signaling pathway, TGF-β signaling pathway, and Rap1 signaling pathway. Selection of drug resistance-associated gene ABCC3 from DEGs for validation with MCAM: qRT-PCR results showed that knockdown of LINC01614 significantly down-regulated the expression of MCAM (P<0.05) and upregulated the expression of ABCC3 on A549 cells (P<0.05). After knockdown of LINC01614, the protein expression of MCAM, was significantly decreased in A549 cells (P<0.05); the IC₅₀ of A549 cells to cisplatin was significantly increased (P<0.05); and the scratch healing rate of A549 cells was also significantly decreased (P<0.05). Conclusion LINC01614 may be associated with the proliferation, invasion, and apoptotic pathways of A549 cells. In addition, LINC01614 may exert its migration ability through MCAM and chemoresistance to cisplatin through ABCC3.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective To explore the effects of ginsenoside Rg1 on blood-brain barrier, neuroinflammation and behavioral function of traumatic brain injury (TBI) mouse model.MethodsThe experiment was divided into two parts. In the first part, 27 SPF male BALB/c mice were randomly divided into blank group, sham operation group and TBI model group, with 9 mice in each group. TBI model group was made by controlled cortical impact (CCI) after craniotomy, while sham operation group was only performed craniotomy without any treatment, and the blank group was not treated at all. The effect of modeling was evaluated after operation. In the second part, 50 male BALB/c mice were randomly divided into sham operation group, three different drug dosage groups and solvent (DMSO) control group, with 8 mice in each group. The drug treatment groups were injected with ginsenoside Rg1 at the doses of 10, 20 and 40 mg/kg respectively 6 hours after TBI model had been successfully established, while the DMSO control group was given the same amount of 1% DMSO for one week, twice a day. Modified neurological severity scores (mNSS) were performed on the 1st, 3rd, 7th and 14th day after modeling, and the blood-brain barrier leakage was detected by Western blotting on the 3rd day after modeling. On the 14th and 16th day, the elevated cross maze test and water maze test were used to detect the neurobehavioral function. On the 28th day after anesthesia and perfusion, the brains were taken out, and the neuroinflammation such as activation of microglia and astrocytes was observed by immunofluorescence staining.ResultsThe expression level of MMP-9, a marker of blood-brain barrier, decreased in ginsenoside Rg1 treatment group (P<0.01). The number of microglia （Iba-1 positive) and astrocyte (GFAP positive) cells decreased significantly (P<0.05), which indicated that neuroinflammation was inhibited, and the best effect was achieved at the dosage of 20 mg/kg (P<0.01). The mNSS of mice in ginsenoside Rg1 treatment group were significantly lower than those in DMSO control group (P < 0.01), and the proportion of times they entered the open arm was significantly higher than that in DMSO control group (P < 0.05). The time ratio in the quadrant where the water maze experimental platform was located and the times of crossing the platform were significantly higher than those in control group (P < 0.05), and the dosage of 20 mg/kg had the best effect.ConclusionThe TBI mouse model was successfully constructed and applied to the study of ginsenoside Rg1 repair of mouse traumatic brain injury. Ginsenoside Rg1 can significantly improve blood-brain barrier, alleviate neuroinflammation and improve neurobehavioral function in TBI model mice, and the effect is the most significant at the dose of 20 mg/kg.

Objective To make finite element analysis and compressive performance test on three-dimensional (3D) printed personalized poly-ether-ether-ketone (PEEK) condyle prosthesis, so as to analyze stress distribution characteristics and mechanical properties of the prosthesis, and to evaluate its clinical value and prospect. Methods The finite element models of PEEK condyle prosthesis, mandible and fixation screw were established by software such as CBCT, Mimics, Geomagic Studio, SolidWorks and ANSYS Workbench. The maximum mastication force was applied, and the maximum stress of the condyle prosthesis and screw, as well as the stress and strain of the mandible were recorded. In order to simulate the actual clinical situation, a special fixture was designed to test compression performance of the condyle prosthesis prepared by the fused deposition modeling (FDM) and selective laser sintering (SLS) at the rate of 1 mm/min. Results The peak stress of the PEEK condyle prosthesis was 10.733 MPa, which was located at the back of the condyle neck. The peak stress of 5 fixing screws was 9.707 5 MPa, which appeared on the 2# and 5# screws near the trailing edge of the mandibular ascending branch. The peak stress of both the prosthesis and the screw was smaller than its yield strength. The maximum pressure of the condyle prosthesis prepared by FDM and SLS was (3 814.7±442.6) N and (1 193.970±260.350) N, respectively. Compared with the SLS preparation, the FDM prepared prosthesis not only had higher compression strength but also better toughness. Conclusions The 3D printed personalized PEEK condyle prosthesis shows uniform stress distributions and good mechanical properties, which can provide the theoretical basis for PEEK as reconstruction material for repairing temporomandibular joint.

Objective:To investigate the potentially inappropriate medication(PIM)among elderly patients with chronic diseases in Shanghai communities and related influence factors.Method:Six community Health service Centers were choosen using stratified sampling. Total 968 elderly patients with chronic diseases who visited to the outpatient clinic of Shanghai Community Health Service Centers from July to August 2018 were included in the study. The PIM was investigated according to the 2015 Beers criteria. The χ 2 test and multivariate logistic regression model were used to analyze factors related to the PIM. Results:The survey showed that 317 elderly patients had PIM with 412 person-doses. In 134 person-doses, the PIM was unrelated to the disease; in 18 person-doses, PIM was caused by interaction of drug with disease/symptoms; in 259 person-doses PIM was related to the drugs that should be cautiously used for elderly; only in 1 person-dose the PIM was caused by the interaction between drugs. The drugs with the highest proportion of PIM were diuretics, benzodiazepines and aspirin. There were significant differences in age, kinds of diseases, kinds of drugs and times of visiting community health service centers between elderly patients with PIM and those without PIM (χ 2=42.28, 35.51, 46.47, 38.46; all P<0.05). The main PIM-related factors were age, kinds of diseases, kinds of drugs and times of visiting community health service centers. Conclusion:The study shows that the prevalence of PIM among elderly chronic diseases patients in Shanghai communities is relatively high, which is associated with the age, kinds of diseases, kinds of drugs and times of visiting community health service centers.

Objective To evaluate the clinical significance of expression of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 3 (MEKK3) in the early-stage cervical cancer. Methods Seventy-one patients with cervical intraepithelial neoplasia (CIN) and 92 patients with early-stage cervical cancer who underwent surgery in Shanxi Provincial Cancer Hospital from March to October 2010 were enrolled. In the same period, 30 normal cervical specimens from hysterectomy due to uterine fibroids were collected as normal controls. The expression of MEKK3 in all specimens was detected by immunohistochemistry and its clinical significance was analyzed. Theχ2 test was performed on the comparison of count data. Results The positive expression rate of MEKK3 was 13.33％ (4/30) in the normal control group, 28.57％(6/21) in the CINⅠgroup, 38.89％(7/18) in the CINⅡgroup, 56.25％(18/32) in the CIN Ⅲgroup and 70.65％(65/92) in the early-stage cervical cancer group. The differences of positive expression rates of MEKK3 in the normal control group, CIN group and early-stage cervical cancer group had statistical significance (χ2=36.870, P<0.05). Compared with the normal control group, the positive rates of MEKK3 in the CINⅢ group and early-stage cervical cancer group increased significantly (χ2 values were 12.458 and 30.251, both P<0.005). The positive rate of MEKK3 in the early-stage cervical cancer group was higher than that in the CIN Ⅰ group (χ2=12.964, P<0.005). The expression of MEKK3 in early-stage cervical cancer were related to histopathological differentiation and lymphatic metastasis (χ2 values were 6.832 and 4.404, both P< 0.05) rather than age, International Federation of Gynecology and Obstetrics (FIGO) stage, histopathological type, tumor diameter and infiltration depth (all P>0.05). Conclusion MEKK3 plays a role in the occurrence, development and prognosis of early-stage cervical cancer, and the detection of MEKK3 may help to assess the degree of early-stage cervical cancer.

Objective To investigate the spontaneous activity of brain neurons in patients with obsessive－compulsive disorder (OCD) under resting state. Methods Forty－eight OCD patients and 50 age－, gender－ and year of education－matched normal controls were enrolled. All the subjects underwent 3.0 T fMRI to acquire resting state brain image. The brain regions with significant differences in amplitude of low－frequency fluctuation (ALFF) between patients and controls were analyzed. Whole－brain functional connectivity (FC) were analyzed using the brain regions with significant differences as seed points, and the correlation between brain regions with significant differences in ALFF and FC analysis and obsessive－compulsive symptoms was analyzed. Results Compared to the control group, the ALFF of left dorsolateral prefrontal cortex increased in patients with OCD (t=4.305, P＜0.001). Compared to the controls, the analysis of whole－brain FC (based on MNI template) with the left dorsolateral prefrontal cortex as the regions of interest showed that the FC strength between the left dorsolateral prefrontal cortex and right orbital inferior frontal cortex (t=3.897, P＜0.001), left anterior cingulate cortex (t=3.370, P＜0.001), right anterior cingulate cortex (t=4.299, P＜0.001), left middle cingulate cortex (t=3.220, P＜0.001), right middle cingulate cortex (t=4.607, P＜0.001) enhanced; the FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus (t=－4.630, P＜0.001) weakened in patients with OCD. The FC between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus was negatively correlated with obsessions score(r=－0.369, P=0.014), compulsions score (r=－0.392, P=0.009) and total score (r=－0.393, P=0.008) of the Yale－Brown obsessive compulsive scale (Y－BOCS). Conclusion In patients with OCD, spontaneous neural activity of the left dorsolateral prefrontal cortex is enhanced in resting state, and the FC with multiple brain regions is abnormal. The FC strength between the left dorsolateral prefrontal cortex and the left opercular part of inferior frontal gyrus is associated with obsessive－compulsive symptoms.