Objective This study aimed to identify PAX9 variants in non-syndromic tooth agenesis families of Chi-na,as well as to analyze the genotype-phenotype of non-syndromic tooth agenesis caused by PAX9 variants,which can provide a basis for the genetic diagnosis of tooth agenesis.Methods We collected the data of 44 patients with non-syn-dromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023.Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members,and the variants were verified by Sanger sequencing.Pathogenicity analysis and function prediction of the variants were per-formed using bioinformatics tools.The correlation between the genotype of PAX9 variant and its corresponding pheno-type was examined by reviewing 55 publications retrieved from PubMed.The studies involved 232 tooth agenesis pa-tients with PAX9 variants.Results A novel PAX9 c.447delG(p.Pro150Argfs*62)and a reported PAX9 c.406C>T(p.Gln136*)were identified in two Chinese families.Through bioinformatics analysis and three-dimensional structural mod-eling,we postulated that the frameshift variant was pathogenic.The outcome was the premature cessation of PAX9 pro-tein,which caused severe structural and functional deficiencies.Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars.Conclusion We identified the novel PAX9 c.447delG(p.Pro150Argfs*62)in a Chinese family of non-syndromic oligodontia,expanding the known variant spectrum of PAX9.The most susceptible tooth position for PAX9 variants of tooth agenesis was the second mo-lars and the deciduous molars during the deciduous dentition.

Objective To investigate the value of tranexamic acid combined with aspirin,low molecular weight heparin calcium in regulating inflammatory mediators and TEG in blood management of Total knee arthroplast(TKA).Methods 120 elderly patients with TKA in our hospital from January 2020 to October 2022 were randomly divided into group A(n=60)and group B(n=60).They were given tranexamic acid+aspirin and tranexamic acid+low molecular weight heparin calcium,respectively,for 2 weeks.Perioperative indexes,complications[lower limb deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection],blood transfusion rate,adverse reactions(gastrointestinal discomfort,subcutaneous ecchymosis),TEG parameters[coagulation reaction time(R),blood coagulation time(K),maximum amplitude(MA),coagulation angle(α)],inflammatory mediators[soluble CD40 ligand(sCD40L),Toll-like receptor 4(TLR4),tumor necrosis factor(TNF-α)],vascular endothelial injury factors[soluble thromboregulatory protein(sTM),vascular endothelial cell growth factor(VEGF),E-selectin]were compared between the two groups.Results There was no significant difference in the 24 h postoperative drainage volume,latent blood loss,total blood loss,intraoperative blood loss,Hb and HCT levels 72 h after surgery between the two groups(P＞0.05).There was no statistically significant difference in TEG parameters between the two groups,at different time points,and between groups at different time points(P＞0.05);The serum levels of TLR4,sCD40L and TNF-α in group A were lower than those in group B 2 weeks after surgery(P＜0.05).The levels of plasma sTM and serum VEGF and E-selectin in group A were lower than those in group B 2 weeks after surgery(P＜0.05).There was no significant difference in the incidence of deep vein thrombosis(DVT),intermuscular vein thrombosis(MCVT),incision infection and blood transfusion rate between group A and group B(P＞0.05).There was no significant difference in the total incidence of adverse reactions between group A and group B(P＞0.05).Conclusion Compared with the combination of low molecular weight heparin calcium,the combination of tranexamic acid and aspirin can protect vascular endothelium and inhibit inflammatory response.However,both can maintain the patient's coagulation function and avoid massive blood loss or thrombosis.There is no significant difference in safety and effectiveness.

Objective:To construct the liver organoid infected with hepatitis D virus (HDV), and to investigate the role of the sodium taurocholate cotransporting polypeptide (NTCP) receptor inhibitor bulevirtide in inhibiting viral replication.Methods:Hepatocyte-like cells (HLC) differentiated from induced pluripotent stem cells (iPSC) were seeded onto inverted colloidal crystal polyethylene glycol scaffolds (ICC) to construct liver organoids. After transfecting human hepatocelluar carcinoma cells (HuH7 cells) with plasmids, HDV particles were harvested from the supernatant, while HBV particles were extracted from the HepG2.2.15 cell supernatant. The liver organoids were infected with both HBV and HDV particles, and the negative control group without HDV infection was set up. The microstructure of the liver organoid units and the expression of hepatitis D antigen (HDAg) and hepatitis B surface antigen (HBsAg) were observed under laser scanning confocal microscope by immunofluorescence method. The protein levels of NTCP and HDAg in the liver organoids were detected by Western blotting. Bulevirtide was added before HDV infection (bulevirtide pre group) and 24 hours after infection (bulevirtide post group), and interferon-alpha (IFN-α) was also added after 24 hours infection (IFN-α group), and a control group without drug treatment was set up. HDV replication was compared among the four groups after drug intervention. Real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) was used to measure the relative mRNA expression levels of Nanog homeobox (NANOG), sex determining region Y-box (SOX)2, SOX17, forkhead box protein A2 (FOXA2), hepatocyte nuclear factor 4 alpha (HNF-4α), albumin (ALB), alpha-fetoprotein (AFP), NTCP during the differentiation of iPSC, and the mRNA expression of HDV after the drug intervention of the four groups. Statistical analysis was performed using two independent sample t tests. Results:Within 21 days of the differentiation of iPSC into HLC, the mRNA expression level of NANOG gradually decreased, while the expression levels of SOX17, FOXA2 initially increased then decreased, and the expression levels of the HNF-4α, ALB, AFP and NTCP progressively increased. The protein level of NTCP in iPSC (0.118±0.003) was lower than that in HLC (1.315±0.073), and the difference was statistically significant ( t=11.92, P<0.001).The protein level of HDAg in the liver organoids after HDV infection was higher than that in the negative control group without HDV infection (1.284±0.128 vs 0.157±0.040), and the difference was statistically significant ( t=23.27, P<0.001).Laser scanning confocal microscopy showed three-dimensional spheroid structures and high expressions of HDAg and HBsAg at the 14th day of infection.Compared with the control group (1.000±0.077), the HDV mRNA expressions in both IFN-α group (0.453±0.028) and bulevirtide pre group (0.136±0.012) decreased after three days of drug intervention. The differences were statistically significant ( t=19.95 and 33.15, respectively, both P<0.001). However, there was no significant difference in HDV mRNA expressions between the bulevirtide post group (0.968±0.069) and the control group ( t=0.94, P>0.05). Conclusions:The liver organoids constructed from iPSC-derived HLC and ICC can simulate human liver functions and successfully be infected by HDV particles. Early blockade with bulevirtide can effectively reduce the level of viral replication in the HDV-infected liver organoids.

Objective:To evaluate the optimization efficacy of anterior quadratus lumborum block at supra-arcuate ligament (SA-AQLB) combined with general anesthesia for laparoscopic gynecological surgery.Methods:Eighty American Society of Anesthesiologists physical status Ⅰ or Ⅱ patients, aged 28-64 yr, weighing 52-78 kg, with height of 154-166 cm, scheduled for elective laparoscopic gynecological surgery, were divided into general anesthesia group (group G, n=40) and SA-AQLB combined with general anesthesia group (group SG, n=40) using a random number table method.In group SG, bilateral SA-AQLB was performed under ultrasound guidance before anesthesia induction, and 0.4% ropivacaine 25 ml plus dexamethasone 5 mg was injected into both sides.Combined intravenous-inhalational anesthesia was applied in both groups.Patient-controlled intravenous analgesia (PCIA) with sufentanil 2 μg/kg (in 150 ml of normal saline) was performed after surgery.The PCIA pump was set up to deliver a 2 ml bolus dose with a 15-min lockout interval and background infusion at 2 ml/h.Visual analogue scale (VAS) scores for abdomen, pelvis and shoulder pain were recorded at 1, 6, 12, 24 and 48 h after operation.Flurbiprofen was used for rescue analgesia when VAS score >4.The occurrence of intraoperative cardiovascular events and amount of sufentanil used during operation were recorded.The time to first pressing the analgesia pump, effective pressing times of PCA, requirement for rescue analgesia and consumption of sufentanil after operation were recorded.The extubation time, time to first flatus after operation, first ambulation time, length of hospital stay and development of postoperative adverse reactions such as nausea and vomiting, urinary retention and respiratory depression within 48 h after operation were recorded. Results:Compared with group G, the incidence of intraoperative hypertension and tachycardia was significantly decreased, the incidence of intraoperative hypotension and bradycardia was increased, the intraoperative consumption of sufentanil was reduced, the extubation time was shortened, the time to first pressing the analgesia pump was prolonged, the effective pressing times of PCA, requirement for rescue analgesia and postoperative consumption of sufentanil were reduced, the time to first flatus, first ambulation time and length of hospital stay were shortened, VAS scores for abdomen, pelvis and shoulder pain were decreased at each time point after operation, and the incidence of nausea and vomiting, urinary retention and respiratory depression after operation was decreased in group SG ( P<0.01). Conclusions:Compared with general anesthesia, the combination of SA-AQLB and general anesthesia can reduce the opioid consumption, inhibit intraoperative stress responses and postoperative hyperalgesia and promote early postoperative recovery when used for the patients undergoing laparoscopic gynecological surgery.

Objective:To assess the left ventricular (LV) myocardial mechanical dysfunction in patients with cirrhosis using ultrasonic layer-specific strain imaging and to explore its value in clinical application.Methods:A total of 80 consecutive cirrhosis patients without cardiovascular diseases were prospectively enrolled from October 2020 to March 2021 in Sichuan Provincial People′s Hospital, 39 of whom were assigned to the compensated group and 41 were assigned to the decompensated group according to the occurrence of portal hypertension. Forty-three healthy volunteers during the same period were randomly recruited as the control group. Transthoracic echocardiography was performed to assess the LV configuration and functional parameters. LV global longitudinal strain in endocardial, middle and epicardial myocardium (GLSendo, GLSmid, GLSepi), and longitudinal strain (LS) in basal, middle and apical segments, and peak strain dispersion (PSD) were obtained using ultrasonic layer-specific strain imaging. ΔLS was calculated by the formula of GLSendo-GLSepi. Then, the differences of related parameters among three groups were compared.Results:①Conventional echocardiography: compared with the control group, the interventricular septum end-diastolic thickness (IVSTd), left ventricular posterior wall end-diastolic thickness (LVPWd), left ventricular mass (LVM) and LVM index (LVMI) were increased in compensated and decompensated groups (all P<0.05), while no significant differences in conventional echocardiographic parameters were identified between the two cirrhosis groups (all P>0.05). ②Global layer-specific strain: compared with the control group, GLSendo, GLSmid, GLSepi and ΔLS were decreased and PSD was increased in compensated and decompensated groups (all P<0.05); Moreover, the decompensated group showed a more impaired GLSendo, GLSmid and GLSepi than compensated group (all P<0.05), whereas there were no significant differences of ΔLS and PSD between the two groups(all P>0.05). ③Segmental layer-specific strain: compared with the control group, LS values of three layers in compensated and decompensated groups were reduced at basal, middle and apical levels (all P<0.05); Compared with the compensated group, LS values of three layers in decompensated group tended to be reduced at above there levels, but only apical segments had significant differences (all P<0.05). Conclusions:There are different degrees of LV mechanical dysfunction in patients with variable severity of cirrhosis. Ultrasonic layer-specific strain imaging has the potential to quantitatively assess the state of cardiac involvement in patients with cirrhosis and to provide visual evidence for the early and accurate diagnosis of myocardial injuries.

Objective: To evaluate the effect of tumor shape and location on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in patients with non-small cell lung cancer (NSCLC), aiming to provide a reference basis for establishing limits of the pulmonary dose-volume parameters during IMRT. Methods: Clinical data of 208 NSCLC patients undergoing radical IMRT from June 2009 to June 2016 were retrospectively analyzed. According to the tumor shape and location, 208 cases were divided into the vertical bar group (n=127) and the horizontal bar group (n=81), the superior lung group (n=103) and the inferior lung group (n=105). Regression model curve was used to evaluate the effect of tumor shape and location upon the common pulmonary dose-volume parameters(V₅, V₂₀, MLD, AVS₅ and AVS₂₀). Results: In all groups, the fitting curves of V₅, V₂₀ and MLD were manifested in the quadratic equation pattern, and AVS₅ and AVS₂₀ in the logarithmic equation manner. In the vertical bar group, the V₅(P=0.015), V₂₀(P=0.047) and MLD (P=0.012) were significantly higher, whereas the AVS₅(P=0.044) was significantly lower compared with those in the horizontal bar group. No statistical significance was observed in AVS₂₀ between two groups (P=0.490). The tumor location exerted significant effect upon V₅ alone (P=0.009). Conclusions When the tumors presents in the vertical bar shape, the limits of the common lung dose-volume parameters are likely to exceed those of tumors in the vertical bar shape. Lung tumors located in the inferior lobe exerts a more significant effect upon the low-dose region volume compared with the tumors in the superior lobe.

Objective:To explore the effectof tumor volume on pulmonary dose-volume parameters by intensity-modulated radiation therapy (IMRT) in non-small cell lung cancer (NSCLC),and to provide a basis for pulmonary dose parameters in IMRT treatment.Methods:A total of 204 patients with NSCLC received IMRT were retrospectively analyzed from June,2009 to October,2013.The prescribed dose of planning target volume (PTV) for primary tumor was 60-66Gy (2.00-2.25 Gy,27-33 times in all).The fractional volume percent of the lung received a dose ＞5 or 20 Gy (V5,V20),and absolute volume of lung received a dose ＜5 Gy (AVS5).The mean lung dose (MLD) in normal tissues were analyzed.Regression model curve was used to analyze them along with the change of primary tumor volume.Results:With the increase in lung tumor volume,the V5,V20 and MLD presented quadratic equation curve,and AVS5 presented logarithmic equation.When the tumor volume,less than a certain value (294.6,283.2,304.9 cm3,respectively),the V5,V20 and MLD increased with tumor size and presented an increased quadratic curve;when the tumor volume was higher than a certain value (294.6,283.2,304.9 cm3 respectively),the V5,V20 and MLD was declined.The AVS5 was declined in a logarithmic curve along with the increase of tumor volume.Conclusion:With the increase in lung tumor volume,the change in rule ofV5,V20,MLD and AVS5 is not completely equivalent.When the tumor volume exceeds a certain boundary value (about 300 cubic centimeter),the corresponding tumor diameter is about 7-8 cm.In addition to the focus on pulmonary V5,V20 and MLD,we should also pay more attention to AVS5 restrictions in establishment ofIMRT in NSCLC.

Objective On patients with mechanical ventilation spontaneous breathing trial (SBT) success, out of breath machine smoothly pulled out after endotracheal intubation for active airway moist sequential therapy of clinical new method and new technology. Methods Between January 2013 and May 2014 respiratory endotracheal intubation implementation of mechanical ventilation with intensive medicine successful withdraw machine pulled out of 135 patients with tracheal intubation, they were divided into group A(68 cases) and group B(67 cases) by random digits table method. The patients in group A were treated with buoy type oxygen device, group B with active airway moist heat treatment unit. The breathing rate, PaO2, SpO2, heart rate, Clinical Pulmonary Infection Score(CPIS) were measured after 72 h of pull out endotracheal intubation in two groups. Sputum viscosity was evaluated by Airway Secretions Score before pull out endotracheal intubation and after 24, 48, 72 h of pull out endotracheal intubation in two groups. Results There were no significant differences between two groups in gender, age, clinical diagnosis, mechanical ventilation time, acute physiology and chronic health evaluation systemⅡrating etc (P>0.05). The breathing rate, heart rate and CPIS score respectively (20.94 ± 0.89), (80.79±4.67) times/min and (7.13 ± 2.54) points after 72 h of pull out endotracheal intubation in group B, and (24.12 ± 0.97), (86.32 ± 5.12) times/min and (8.79±3.56) points in group A, and there were significant differences(t=5.113, 7.298, 5.597, all P<0.01). PaO2, SpO2 were (93.24±1.96) mmHg(1 mmHg=0.133 kPa), 0.973 2±0.014 8 in group B, and (87.35±2.32) mmHg, 0.937 8±0.013 2 in group A, and there were significant differences(t=9.279, 4.548, all P<0.01). There was no significant difference in sputum viscosity before pull out endotracheal intubation between two groups (P>0.05). After 24, 48 and 72 h of pull out endotracheal intubation, group B of patients with sputum viscosity was suitable in group A (Z=-2.684,-2.870,-2.771, all P < 0.01). Conclusions Mechanical ventilation in patients with ventilator buoy type oxygen device for the pull out after endotracheal intubation success does not favor the sputum drainage, improve patients with dyspnea and hypoxemia is not obvious. By positive airway plus temperature humidity to sequential therapy is helpful to correct hypoxemia, improve the patients' respiratory function, reduce the breathing difficulties, reduce sputum viscosity, promote the airway drainage unblocked, shortening the time of lung infection.

Objective:To explore the regular variation pattern of tumor volumes of the patients with non-small cell lung cancer (NSCLC) before and after targeting treatment of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI),and to clarify its clinical value.Methods:The materials of 39 NSCLC patients with EGFR-TKI targeting treatment were retrospectively analyzed. The tumor volumes were detected by volume measurement software of TPS and Image J image processing software,then the absolute and relative tumor volume changes of the NSCLC patients before and after targeting treatment were analyzed by paired sample comparison symbol Wilcoxon rank test. Results:The absolute tumor volumes (mm3 )of the patients with NSCLC before and 1 month after targeting treatment were 14 822.11 (7 524.73,54 999.41)and 7 954.42 (3 499.73,29 396.83),respectively, and there was statistically significant difference (Z=-3.257,P=0.001);the absolute tumor volumes of the patients with NSCLC 1 and 2 months after targeting treatment were 8 358.47 (4 394.36,24 430.05)and 7 028.76 (3 634.98,21 056.71),respectively,and there also was statisticaliy significant difference (Z=-2.213,P=0.027).When the original tumor volume before targeting treatment was regarded as 1,the relative tumor volume of 1 month after targeting theatment was 0.612 6 (0.313 8,0.853 7),and there was significant difference (Z=-3.855,P<0.001);the relative tumor volumes of 1 month and 2 months after targeting treatment were 0.608 4 (0.364 3,1.044 3)and 0.423 0 (0.248 8,0.877 7),respectively,and there also was statistically significant differernce (Z=-2.173,P=0.030);but the differences between other consecutive months (from 3 months to 6 months)had no statistically significant differences (P>0.05);the changes of tumor relative volume presented platform stage after 3 months.The tumor relative volumes of 7-9 months after EGFR-TKI treatment reached the bottom.Conclusion:The average primary tumor volume of the NSCLC patients is obviously reduced 1 and 2 months after TKI targeting treatment. It may be optimal to carry out radiotherapy in 3-9 months after EGFR-TKI targeting treatment.

PurposeArtifacts of metal implantation severely affect image quality of CT or MRI examination, which restricts the display of local soft tissue lesions after orthopaedic surgery. This study aims to explore the application value of ultrasound examination in local soft tissue lesions after metal implant surgery.Materials and Methods Seventy patients with metal implantation after various orthopedic surgeries received US examination, and such sonographic features were recorded as lesion morphology, size, internal echo, edge, with/without capsule and calcification, and blood flow. Moreover, the clinical and radiologic data of patients like X-ray, CT and MRI were compared with the US results so as to determine the sensitivity of ultrasonic examination.Results The peripheral nerve injury might lead to thickened swelling and echo reduction. Ultrasonography revealed 20 cases of hematoma formation, 5 cases of abscess, 5 cases of pseudoaneurysm, 3 cases of myositis ossificans, 15 cases of bone tumor recurrence and 12 cases of peripheral nerve injury in operative region. Compared with the clinical results , the sensitivity, specificity and accuracy of ultrasound diagnosis of the study reached 89.4%, 75.0% and 88.6%, respectively, which were signiifcantly higher than those of X-ray, CT and MRI (χ2=78.642, 46.596 and 61.371,P<0.01). The ultrasonic results showed that most hematomas had clear boundary with homogenous echo inside to echo-free zone. Abscesses mostly displayed cystic or hybrid echo with floatable intracavitary pus spots echo, and no blood flow signal existed in the central area of color Doppler. Pseudoaneurysm in the US showed cystic mass around artery, blood flow rotating in capsule, and the typical two-stage bi-spectrum signal in the neck of capsule. Myositis ossiifcans showed intramuscular irregular hyperecho with acoustic shadow. When bone tumor recurred, US showed hypoechoic soft tissue mass with moth-eaten bone destruction, and blood flow signals within the mass were often detected.Conclusion Ultrasonography has relatively high accuracy in observing soft tissues around metal implantation, which can be used as a premier method.