ObjectiveTo investigate the potential mechanism of action of the Qufeng Tongqiao Cough-relieving Decoction （祛风通窍止咳方， QTCD） in the treatment of upper airway cough syndrome （UACS）. MethodsTwenty-four guinea pigs were randomly divided into blank group， model group， traditional Chinese medicine （TCM） group， and inhibitor group， with six guinea pigs in each group. Except for the blank group， guinea pigs were sensitized with ovalbumin and aluminum hydroxide via intraperitoneal injection， followed by ovalbumin nasal drops combined with smoke exposure to establish the UACS model. After modeling， the TCM group was administered QTCD 0.9 g/（100 g·d） by gavage， the inhibitor group received the transient receptor potential vanilloid receptor 4 （TRPV4） inhibitor GSK2193874 1 mmol/L， 5 min by nebulisation， and the blank group and model group were given 2 ml/（100 g·d） normal saline by gavage once daily. After 7 days of treatment， a cough provocation test was performed using 0.4 mol/L citric acid. The levels of IgE in serum and inflammatory cytokines， including interleukin-6 （IL-6）， interleukin-8 （IL-8） in serum， bronchoalveolar lavage fluid （BALF）， and nasal lavage fluid （NLF） were detected by enzyme-linked immunosorbent assay （ELISA）. Histopathological changes in lung and nasal mucosal tissues were observed by hematoxylin-eosin （HE） staining. Immunohistochemistry was used to detect the protein levels of TRPV4， substance P （SP）， and calcitonin gene-related peptide （CGRP） in lung and nasal mucosal tissues. Real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of TRPV4， SP， and CGRP in lung tissues. ResultsHE staining showed significant structural damage and infiltration of inflammatory cells in the lung and nasal mucosal tissues in the model group， while the TCM group and inhibitor group showed improved pathological changes. Compared with the blank group， the model group showed increased cough frequency， serum IgE level， and IL-6 and IL-8 levels in serum， BALF， and NLF. The protein levels of TRPV4， SP， and CGRP in lung and nasal mucosal tissues and their mRNA expression were elevated （P＜0.05 or P＜0.01）. Compared with the model group， the TCM group and inhibitor group showed reduced cough frequency， serum IgE level， and TRPV4 and SP mRNA expression in lung tissues. The TCM group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， and reduced TRPV4 and CGRP protein levels in lung and nasal mucosal tissues. The inhibitor group showed reduced IL-6 and IL-8 levels in serum， BALF， and NLF， reduced IL-6 in BALF， reduced IL-8 in NLF， and decreased TRPV4， SP， and CGRP protein levels in lung tissues and SP and CGRP protein levels in nasal mucosal tissues （P＜0.05 or P＜0.01）. Compared with the TCM group， the inhibitor group had increased serum IgE， IL-6， and IL-8 levels， increased IL-6 level in BALF， and increased IL-8 levle in NLF， but decreased SP protein level in lung tissues and increased TRPV4 and SP mRNA expression in lung tissues （P＜0.01）. ConclusionQTCD effectively reduces cough frequency in the UACS guinea pig model. Its mechanism may involve inhibiting the activation of the TRPV4 pathway， improving airway neurogenic inflammation， alleviating inflammatory responses， and reducing cough hypersensitivity.

BACKGROUND:The lower cervical vertebral pedicle is the main stress site of the posterior column of the spine,which is of great significance for the maintenance of the stability of the human center of gravity and the reduction of shock.At present,there are few reports on the characteristics of the internal bone trabeculae,and the characteristics of the joint site of the vertebral pedicle with the articular process and the vertebral body.It is urgent to understand the fine anatomical structure of the vertebral pedicle and the relationship and function of each part. OBJECTIVE:To observe the microanatomical morphology of the vertebral pedicle by Micro-CT scanning of cervical vertebra specimens,and to measure and analyze the microstructure and morphometric parameters of the bone trabecula in the cervical pedicle under normal conditions to evaluate the safety performance of the cervical spine. METHODS:Micro-CT scanning was performed on 31 sets of cervical vertebrae C3-C7.By checking and reconstructing the areas of interest in the bone trabecular within the vertebral pedicle,the morphological characteristics and distribution direction of the bone trabecular within the cervical pedicle were observed,and the bone microstructure parameters were detected,and the differences in the bone microstructure of the C3-C7 vertebral pedicle were analyzed and compared. RESULTS AND CONCLUSION:(1)The Micro-CT images showed that the honeycomb bone trabeculae of the pedicle of the lower cervical spine presented a complex network of microstructures.The trabeculae near the cortical bone were lamellar and relatively compact,extending forward toward the vertebral body and backward toward the articular process lamina.Abatoid bone trabeculae extended into the medullary cavity and transformed into a network structure,and then into rod-shaped bone trabeculae.The rod-shaped bone trabeculae were sparsely distributed in the medullary cavity.(2)Statistical results of morphological parameters of bone trabeculae showed that bone volume fraction values in C4 and C5 were higher than that in C7(P＜0.05).The bone surface/bone volume value in C7 was higher than that in C3,C4 and C6(P＜0.05).The bone surface density of bone trabeculae in C7 was higher than that in C3,C4,C5 and C6(P＜0.05).Trabecular thickness in C7 was higher than that in C3,C4 and C5(P＜0.05).Bone surface/bone volume and bone surface density of the left pedicle bone trabecular were greater than those on the right side(P＜0.05).(3)The microstructural changes of C3-C7 were summarized,in which the load capacity and stress of the C7 pedicle were poor,and the risk of injury was high in this area.

Objective:To investigate the incidence of venous thromboembolism (VTE) in patients with esophageal cancer (EC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 8 458 EC patients who were admitted to Sichuan Cancer Hospital from January 2017 to December 2021 were collected. There were 6 923 males and 1 535 females, aged (64±9)years. There were 3 187 patients undergoing surgical treatment, and 5 271 cases undergoing non-surgical treatment. Observation indicators: (1) incidence of VTE in EC patients; (2) treatment and outcomes of patients with VTE. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was analyzed using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was analyzed using the nonparameter rank sum test. Count data were expressed as absolute numbers or percentages, and comparison between groups was analyzed using the chi-square test or Fisher exact probability. Comparison of ordinal data was analyzed using the nonparameter rank sum test. Results:(1) Incidence of VTE in EC patients. Of 8 458 EC patients, 175 cases developed VTE, with an incidence rate of 2.069%(175/8 458). Among 175 VTE patients, there were 164 cases of deep venous thrombosis (DVT), 4 cases of pulmonary embolism (PE), 7 cases of DVT and PE. There were 59 surgical patients and 116 non-surgical patients. There was no significant difference in thrombus type between surgical and non-surgical EC patients with VTE ( χ2=1.95, P>0.05). Of 3 187 surgical patients, the incidence of VTE was 1.851%(59/3 187), including an incidence of 0.157%(5/3 187) of PE. PE accounted for 8.475%(5/59) of surgical patients with VTE. Of 5 271 non-surgical patients, the incidence of VTE was 2.201%(116/5 271), including an incidence of 0.114%(6/5 271) of PE. PE accounted for 5.172%(6/116) of non-surgical patients with VTE. There was no significant difference in the incidence of VTE or PE between surgical patients and non-surgical patients ( χ2=1.20, 0.05, P>0.05). (2) Treatment and outcomes of patients with VTE. Among 175 EC patients with VTE, 163 cases underwent drug treatment, and 12 cases did not receive treatment. Among 163 cases with drug therapy, 158 cases underwent anticoagulant therapy, 5 cases were treated with thrombolysis. All the 163 patients were improved and discharged from hospital. Conclusions:The incidence of VTE in patients with EC is relatively low, as 2.069%. There is no significant difference in the incidence of VTE or thrombus type between surgical EC patients and non-surgical EC patients.

Background::Bladder cancer, characterized by a high potential of tumor recurrence, has high lifelong monitoring and treatment costs. To date, tumor cells with intrinsic softness have been identified to function as cancer stem cells in several cancer types. Nonetheless, the existence of soft tumor cells in bladder tumors remains elusive. Thus, our study aimed to develop a microbarrier microfluidic chip to efficiently isolate deformable tumor cells from distinct types of bladder cancer cells.Methods::The stiffness of bladder cancer cells was determined by atomic force microscopy (AFM). The modified microfluidic chip was utilized to separate soft cells, and the 3D Matrigel culture system was to maintain the softness of tumor cells. Expression patterns of integrin β8 (ITGB8), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were determined by Western blotting. Double immunostaining was conducted to examine the interaction between F-actin and tripartite motif containing 59 (TRIM59). The stem-cell-like characteristics of soft cells were explored by colony formation assay and in vivo studies upon xenografted tumor models. Results::Using our newly designed microfluidic approach, we identified a small fraction of soft tumor cells in bladder cancer cells. More importantly, the existence of soft tumor cells was confirmed in clinical human bladder cancer specimens, in which the number of soft tumor cells was associated with tumor relapse. Furthermore, we demonstrated that the biomechanical stimuli arising from 3D Matrigel activated the F-actin/ITGB8/TRIM59/AKT/mTOR/glycolysis pathways to enhance the softness and tumorigenic capacity of tumor cells. Simultaneously, we detected a remarkable up-regulation in ITGB8, TRIM59, and phospho-AKT in clinical bladder recurrent tumors compared with their non-recurrent counterparts.Conclusions::The ITGB8/TRIM59/AKT/mTOR/glycolysis axis plays a crucial role in modulating tumor softness and stemness. Meanwhile, the soft tumor cells become more sensitive to chemotherapy after stiffening, that offers new insights for hampering tumor progression and recurrence.

Objective To investigate the mechanism of Yes-associated protein 1(YAP1)ameliorating aristolochic acid 1(AAI)-induced liver injury in mice based on untargeted metabolomics techniques.Methods There were 83-week-old male hepatocyte-specific Yap1 gene knockout mice(genotyped as Yap1Flox/Flox,Albumin-Cre,aka.Yap1LKO)were randomly selected as the Yap1LKO+AAI group,and 8 Yap1Flox control mice as the Yap1Flox+AAI group.Both groups were injected intraperitoneally with AAI at a dose of 2.5 mg·kg-1·d-1 for 14 consecutive days.Genotypes were identified by tail PCR;serum alanine transaminase(ALT)and aspartate transaminase(AST)activities were determined by microplate assay;histopathological changes of liver tissue were observed by HE staining;and the protein expression of YAP1 in liver tissue was determined by immunohistochemistry.The untargeted metabolomics approach was used to analyze the liver tissue differential metabolites,and the samples were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbit trap high-resolution mass spectrometry,and the differential metabolites were screened by principal component analysis(PCA),Partial least square-discriminant analysis(PLS-DA),and orthogonal partial least squares-discriminant analysis(OPLS-DA);using HMDB database and METLIN database to identify metabolites,and the pathway enrichment of differential metabolites was analyzed by KEGG database.Results(1)After 14 days of AAI induction,the increase of body mass in Yap1LKO mice was lower than that in Yap1Flox mice,but there was no statistical significance(P＞0.05).On day 14,compared with the Yap1Flox+AAI group,the serum ALT and AST enzyme activities in the Yap1LKO+AAI group of mice were significantly increased(P＜0.05),and the histopathological damage of the liver was significantly aggravated.The livers of the Yap1Flox mice had a positive protein expression of YAP1,whereas the Yap1LKO mice did not have a positive protein expression of YAP1.(2)A total of 139 differential metabolites with significant changes(VIP＞1 and P＜0.05)were screened by metabonomic analysis;compared with Yap1LKO+ AAI group,62 liver metabolites in Yap1Flox+AAI group were up-regulated,including choline,taurine,hypotaurine,α-linolenic acid,eleostearic acid,chenodeoxycholic acid and so on.Seventy-seven metabolites were down-regulated including glycerophosphocholine,L-phosphatidylcholine,L-glutamine,L-serine,L-glutathione,5-methionine,phenylalanine,glucose 6-phosphate,lactic acid,uric acid glycosides,etc..KEGG-enriched pathways were mainly choline metabolism,glycerophospholipid metabolism,insulin resistance,glutathione metabolism,etc..Conclusion Hepatocyte-specific Yap1 gene knockout exacerbated AAI-induced liver injury in mice,and YAP1 was involved in the regulation of choline metabolism and glycerophospholipid metabolism through the up-regulation of unsaturated fatty acids,such as choline and taurine,which ameliorated AAI-induced liver injury in mice.

Objective To evaluate the characteristics of the mass balance and pharmacokinetics of[14 C]birociclib in Chinese male healthy volunteers after a single oral administration.Methods This study used a 14 C labeled method to investigate the mass balance and biological transformation of birociclib in human.Subjects were given a single oral dose of 360 mg/50 pCi of[14 C]birociclib suspension after meals.The blood,urine,and fecal samples were collected at specified time points/intervals after administration.The radiation levels of 14 C labeled birociclib-related compounds in the blood,plasma,urine,and feces were analyzed using liquid scintillation counting.In addition,a combination of high-performance liquid chromatography and on-line/off-line isotope detectors was used to obtain radioactive isotope metabolite spectra of plasma,urine,and fecal samples,and high-resolution mass spectrometry was used to identify the main metabolites.Results A total of 6 healthy male subjects were enrolled in this study.The median peak time of radioactive components in plasma was 5.00 h and the average terminal elimination half-life was 43.70 h after administration.The radioactive components were basically excreted and cleared from the body within 288.00 hours after administration,and average cumulative recovery rate of radioactive drugs was(94.10±8.19)％.The radioactive drugs were mainly excreted through feces,accounting for(84.60±7.10)％of the dose of radioactive drugs administered.Urine was the secondary excretory pathway,accounting for 9.41％of the dose of radioactive drugs administered.Metabolic analysis indicated that the prototype drug was the main radioactive components in plasma samples.The main metabolites in plasma were RM4(XZP-5286),RM6(XZP-3584),and RM7(XZP-5736).The drugs were mainly cleared from the body in the form of prototype drugs and metabolites.In addition to prototype drugs,a total of 9 metabolites were identified and analyzed in plasma,urine,and fecal samples,all of which were phase 1 metabolites.The main metabolic and clearance pathways of drugs in the body were deethylation,diisopropylat ion,oxidation,etc.Conclusion After a single oral administration of[14C]birociclib suspension to healthy subjects,it was mainly cleared from the body in the form of prototype drugs and metabolites,with feces as the main excretory pathway and urine as the secondary excretory pathway.Drugs mainly undergo metabolic reactions in the body,such as deethylation,diisopropylation,and oxidation.The subjects were well tolerance after administration.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To evaluate the clinical value of optic nerve sheath diameter(ONSD)measured on thin-slice CT scan in the diagnosis and prognostic assessment of cerebral venous sinus thrombosis(CVST).Methods The clinical data of patients with CVST,who were admitted to the First Affiliated Hospital of Nanjing Medical University of China to receive treatment from January 1,2016 to December 31,2022,were retrospectively analyzed.The difference in ONSD was compared between CVST patients and normal population,the postoperative changes in ONSD was analyzed.Results A total of 49 patients with CVST(CVST group)and 49 normal persons having no brain disorders(control group)were enrolled in this study.In CVST group,the preoperative ONSD was(5.33±0.50)mm,which was significantly higher than(4.40±0.40)mm in control group(P＜0.001),the postoperative ONSD remarkably decreased to(4.98±0.59)mm(P＜0.01).The difference value between postoperative ONSD and preoperative ONSD in the patients receiving pure anticoagulation treatment was not statistically significant different from that in the patients receiving endovascular treatment[(-0.43±0.22)mm vs.(-0.40±0.42)mm,P=0.84].The preoperative ONSD in the patients having intracranial hemorrhage and in the patients having no intracranial hemorrhage was(5.26±0.51)mm and(5.41±0.49)mm respectively(P=0.31),and the difference value between postoperative ONSD and preoperative ONSD was(-0.39±0.40)mm and(-0.45±0.25)mm respectively(P=0.66).At the three-month follow-up visit,the difference in ONSD between the patients having a good prognosis(mRS score being 0-2 points)and the patients having a poor prognosis was not statistically significant(P＞0.05).Conclusion ONSD that is measured on plain head CT scan can be used as a response indicator of elevated intracranial pressure in CVST patients,which can be used to monitor the changes in intracranial pressure before and after treatment,but its value in assessing the curative efficacy of different therapeutic methods needs to be further explored.

Objective To investigate the effect of orthopedic distractor assisted reduction and percutaneous plate implantation in the treatment of distal tibial fractures.Methods 120 patients with distal tibial fractures treated in Wendeng orthopedic hospital of Shandong Province from January 2019 to January 2021 were randomly divided into two groups:the control group(60 cases,percutaneous plate implantation and internal fixation under traditional manual reduction)and the observation group(60 cases,orthopedic distractor assisted manual reduction and percutaneous plate implantation and internal fixation).The treatment effect,intraoperative indexes and postoperative fracture recovery of the two groups were compared,and the complications of the two groups were recorded and compared.Results After treatment,there was no significant difference in the excellent and good rate of fracture healing in the observation group(P＞0.05);The operation time[(72.56±27.54)min]and fracture healing time[(16.45±4.59)w]of the observation group were shorter than those of the control group[(89.94±28.20)min and(21.15±4.54)w],and the amount of intraoperative bleeding in the observation group[(82.27±20.14)ml]was less than that of the control group[(90.12±21.48)ml],the differences were statistically significant(P＜0.05);12 months after operation,the knee joint score of American Special Surgery Hospital(HSS)and ankle hindfoot score of American ankle Orthopedic Association(AOFAS)in the observation group[(85.24±7.52)and(84.58±7.29)]were lower than those in the control group[(74.45±7.64)and(74.56±6.38)](P＜0.05).There was no significant difference in the total incidence of complications between the two groups(P＞0.05).Conclusion Orthopedic distractor assisted reduction and percutaneous steel plate implantation and internal fixation have good curative effect,which can effectively reduce the amount of intraoperative bleeding,shorten the operation time,and have a good recovery of foot and ankle function after operation.

Objective To observe whether SaCoVLM laryngeal mask can cause gastroesophageal reflux when the body position changes(lithotomy position and supine position).Methods A total of 70 patients were selected for elective surgery in Shanghai General Hospital from Dec 1st,2021 to Sep 30th,2022.There were 35 patients with ureteroscopy in urology and 35 patients with ankle surgery in trauma orthopedics selected as lithotomy position group and supine position group,respectively.Under SaCoVLM laryngeal mask anesthesia,a dual probe pH electrode was placed in the esophagus to continuously monitor the pH value in the esophagus.The pH values and their changing trends in the lithotomy position and supine position of the esophagus were compared under general anesthesia with SaCoVLM laryngeal mask ventilation,and the possibility of gastroesophageal reflux occurring in both positions was explored.Results The peak airway pressure at each time point(5 min,10 min,15 min,20 min and 30 min)after body position was determined in the two groups,and it in lithotomy position group was significantly higher than that in supine position group,and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min after laryngeal mask insertion,and it in lithotomy position group(6.045±0.490)was significantly lower than the supine group(6.532±0.366),and the difference was statistically significant(P＜0.05).The middle and upper esophageal pH values of the two groups were compared 10 min and 15 min after laryngeal mask insertion.They in lithotomy position group were significantly lower than those in supine position group,and the differences were statistically significant(10 min:6.045±0.490 vs.6.532±0.366,P=0.031;15 min:5.828±0.487 vs.6.474±0.411,P=0.048).There was no significant difference in the pH of the middle and upper esophagus between the two groups at 1,5,20 and 30 minutes of laryngeal mask insertion.There was no significant difference in the pH value of the esophageal opening between the two groups at each time point after laryngeal mask insertion.Conclusion Under SaCoVLM laryngeal mask ventilation,the risk of gastroesophageal reflux during lithotomy surgery may be higher than during supine surgery.