GPR126, also known as ADGRG6, is one of the most deeply studied aGPCRs. Initially, GPR126 was thought to be a receptor associated with muscle development and was primarily expressed in the muscular and skeletal systems. With the deepening of research, it was found that GPR126 is expressed in multiple mammalian tissues and organs, and is involved in many biological processes such as embryonic development, nervous system development, and extracellular matrix interactions. Compared with other aGPCRs proteins, GPR126 has a longer N-terminal domain, which can bind to ligands one-to-one and one-to-many. Its N-terminus contains five domains, a CUB (complement C1r/C1s, Uegf, Bmp1) domain, a PTX (Pentraxin) domain, a SEA (Sperm protein, Enterokinase, and Agrin) domain, a hormone binding (HormR) domain, and a conserved GAIN domain. The GAIN domain has a self-shearing function, which is essential for the maturation, stability, transport and function of aGPCRs. Different SEA domains constitute different GPR126 isomers, which can regulate the activation and closure of downstream signaling pathways through conformational changes. GPR126 has a typical aGPCRs seven-transmembrane helical structure, which can be coupled to Gs and Gi, causing cAMP to up- or down-regulation, mediating transmembrane signaling and participating in the regulation of cell proliferation, differentiation and migration. GPR126 is activated in a tethered-stalk peptide agonism or orthosteric agonism, which is mainly manifested by self-proteolysis or conformational changes in the GAIN domain, which mediates the rapid activation or closure of downstream pathways by tethered agonists. In addition to the tethered short stem peptide activation mode, GPR126 also has another allosteric agonism or tunable agonism mode, which is specifically expressed as the GAIN domain does not have self-shearing function in the physiological state, NTF and CTF always maintain the binding state, and the NTF binds to the ligand to cause conformational changes of the receptor, which somehow transmits signals to the GAIN domain in a spatial structure. The GAIN domain can cause the 7TM domain to produce an activated or inhibited signal for signal transduction, For example, type IV collagen interacts with the CUB and PTX domains of GPR126 to activate GPR126 downstream signal transduction. GPR126 has homology of 51.6%-86.9% among different species, with 10 conserved regions between different species, which can be traced back to the oldest metazoans as well as unicellular animals.In terms of diseases, GPR126 dysfunction involves the pathological process of bone, myelin, embryo and other related diseases, and is also closely related to the occurrence and development of malignant tumors such as breast cancer and colon cancer. However, the biological function of GPR126 in various diseases and its potential as a therapeutic target still needs further research. This paper focuses on the structure, interspecies differences and conservatism, signal transduction and biological functions of GPR126, which provides ideas and references for future research on GPR126.

Aim To investigate the enhanced efficacy and reduced toxicity of GanoExtra in combination with cyclophosphamide(CTX)on inhibiting lung metastasis and immune function in mice.Methods The CCK-8 method was used to verify the cytotoxic effects of Gano-Extra on MCF-7 and 4T1 tumor cells.In vivo experi-ment,a mouse model of lung metastasis of breast canc-er was established by injecting 4T1 tumor cells into the tail vein,which was divided into four groups including 4T1 model group,CTX group,GanoExtra group and GanoExtra+CTX group.The control group was set.After 21 days,the mice were euthanized under anes-thesia,and the body weight of the mice was recorded.Average lung index and spleen index were calculated.The mouse spleen lymphocyte transformation experi-ment was used to determine the activity of spleen cells.The NK cell activity assay was used to determine the activity of NK cells.Blood cells were determined in mouse blood samples.Flow cytometry was used to de-termine the levels of CD4+and CD8+T cells in blood samples.ELISA was used to measure the levels of TNF-α and IL-6 in serum.HE staining was used to ob-serve the pathological morphological changes in tumors and various tissues;and CFSE staining was used to de-termine the proliferative effect of GanoExtra on CD8+cells.Results In vitro GanoExtra at 50 mg·L-1 sig-nificantly inhibited the activity of MCF-7 and 4T1 tumor cells.In the breast cancer pulmonary metastasis model,compared with the model group,the spleen in-dex and blood WBCs content were significantly re-duced,while the activity of NK cells,spleen cells,and the proportion of RBCs,CD 3+and CD 8+T cells in the blood were significantly increased.At the end of the treatment,compared with the CTX group,the number of lung metastases and lung index of the Gano-Extra+CTX group were significantly reduced,and the levels of HGB,CD8+cells,IL-6,and TNF-α in the blood of mice were significantly increased.GanoExtra at 10 mg·L-1 significantly promoted the proliferation of CD8+T cells in vitro.Conclusions GanoExtra can enhance the inhibitory effect of CTX on tumor metasta-sis,alleviate adverse reactions such as splenomegaly and pulmonary enlargement caused by CTX,and have a health-promoting function of promoting the prolifera-tion of CD8+T cells to enhance the immune efficacy of the body.

OBJECTIVE To study the pharmacodynamics and pharmacokinetics of semaglutide(Sem)capsules in type 2 diabetic model rats.METHODS Male SD rats were divided into the normal control group,type 2 diabetic model group and model+Sem capsules(0.839,1.678 and 2.517 mg·kg-1)groups.A type 2 diabetic rat model was induced by high sugar and high fat diet feeding combined with ip given streptozotocin(STZ)injection.Seven days after modeling,the model+Sem capsules group was ig given Sem capsules at the corresponding dose in a fasting state,once a day,for 14 d.Body mass,fasting blood glucose(FBG),and glycosylated hemoglobin(HbA1c)levels were regularly mea-sured in each group of rats.Plasma from rats in the model+Sem capsules 0.839,1.678 and 2.517 mg·kg-1 groups at different time points was collected at the end of the continuous administration of Sem capsules,and the content of Sem in the plasma of rats was determined by liquid chromatography-tandem mass spectrometry.Concentration-time curves were plotted,and the main pharmacokinetic parameters were fitted by the WinNonlin non-atrial model method.RESULTS Compared with the model group,the body mass of rats in model+Sem capsules dosing groups decreased significantly after 7 and 14 d of Sem capsules intervention(P<0.05,P<0.01),so did FBG(P<0.01)and the HbA1c level(P<0.01).Meanwhile,FBG and HbA1c levels of rats in model+Sem capsules 1.678 and 2.517 mg·kg-1 groups were not significantly different from those of the normal control group after 14 d of Sem capsules intervention,suggesting that FBG and HbA1c levels were basically restored to normal.Phar-macokinetic results showed that the elimination half-life(t1/2)of Sem in plasma after ig administration of Sem capsules 0.839,1.678,and 2.517 mg·kg-1 for 14 d in rats was 7.40±1.34,7.48±0.33 and(8.23±0.90)h,respectively,the peak concentration(Cmax)was 18±9,81±23 and(256±53)μg·L-1,time to peak(Tmax)was 0.06±0.13,1.56±0.88,(1.50±1.00)h,respectively,the area under the curve(AUC0-t)was 158±76 μg·h·L-1,858±310 and(3795±1539)μg·h·L-1,and the accumulation index was 1.12±0.05,1.12±0.01 and 1.15±0.04,respectively.CONCLUSION Sem capsules ig administrated can effectively reduce body mass,FBG and HbA1c levels in type 2 diabetic model rats,and lead to glucose reduction and by mass loss.After 14 d of continuous administration of Sem capsules,there is no accu-mulation of semaglutide in rats in the dose range of 0.839-2.517 mg·kg-1,and the exposure increases with the dose.

Objective:To explore the effect of psychological nursing on the prognosis of male patients with urethral riding inju-ry treated by ureteroscopic urethral catheter implantation(UCI).Methods:This study included 63 male patients with urethral strad-dle injury treated in the General Hospital of Southern Theater Command from February 2020 to March 2023.We divided the patients into a control(n=29)and an experimental group(n=34)according to the odd-or even-numbered days of admission and treated them by ureteroscopic UCI.Meanwhile those of the former group received routine nursing care and the latter underwent psychological nursing intervention in addition.We obtained the Self-Rating Anxiety Scale(SAS)and Self-Rating Depression Scale(SDS)scores of the patients,recorded their postoperative pain scores,catheter-removal time,hospitalization days,postoperative complications and o-verall recovery status,and compared the data collected between the two groups.Results:At 3 days after surgery,both the SAS and SDS scores were significantly lower in the experimental group than in the control(SAS:45.2±2.9 vs 50.4±3.6,P<0.05;SDS:41.9±2.5 vs 48.3±4.0,P<0.05),and so were the pain scores at24 hours(6.2±0.6 vs 6.8±0.9,P<0.05),48 hours(4.9±0.7 vs 6.1±0.8,P<0.05)and 72 hours after surgery(2.5±0.6 vs 3.9±0.9,P<0.05).The hospitalization time was remarkably shorter in the experimental than in the control group([14.1±2.9]vs[16.1±3.4]d,P<0.05),but there was no statistically significant difference in the time of postoperative catheterization between the two groups of patients([19.3±3.7]vs[19.6±4.4]d,P>0.05).A30-day postoperative follow-up found2 cases of difficult urination in the control group but no com-plications in the experimental group.Conclusion:Ureteroscopic UCI is a safe,effective and minimally invasive treatment method for male urethral riding injury,and psychological nursing helps not only shorten the time of catheterization and hospitalization but also a-void postoperative complications.

AIM To control the quality of Bupleurum chinense DC.METHODS The analysis was performed on a 35℃ thermostatic Venusil XBP C18 column(250 mm×4.6 mm,5 μm),with the mobile phase comprising of acetonitrile-water flowing at 1.0 mL/min,and the detection wavelength was set at 210 nm.The HPLC fingerprints were established,after which the contents of saikosaponin A,saikosaponin B2,saikosaponin C,saikosaponin D,saikosaponin E,saikosaponin F and 6″-O-acetylsaikosaponin A were determined,and principal component analysis was made.RESULTS There were thirteen common peaks in the fingerprints for twelve batches of medicinal materials with the similarities of 0.970-0.995.Seven constituents showed good linear relationships within their own ranges(R2≥0.999 8),whose average recoveries were 90.75%-100.91% with the RSDs of 1.6%-4.0% .Various constituents demonstrated similar contents in medicinal materials originated in Inner Mongolia and Shanxi.CONCLUSION This precise,accurate and stable method can be used for the quality evaluation of B.chinense.

Objective:To compare the effect of self-radiopaque markers guiding physician-modified fenestration, chimney technique and hybrid Ⅳb technique on reconstruction of left subclavian artery (LSA) in endovascular treatment of aortic dissection (TEVAR).Methods:The clinical and follow-up data of 312 TEVAR patients treated with LSA blood supply reconstruction technology from Jan 2016 to Dec 2019 at Fuwai hospital were retrospectively analyzed.Results:There were 35 patients in the hybrid Ⅳb technique group, 93 in the chimney technique group, and 184 in the in vitro fenestration group. The follow-up period ranged from 12 to 24 months. No artificial blood vessel and stent occlusion occurred in all patients during follow-up, and the LSA blood flow was unobstructed. A total of 19 patients had endoleak by the last follow-up, and there was no statistical difference between the three groups. Eleven patients underwent reintervention surgery, all were from chimney technique group and in vitro fenestration group, with no statistical difference ( P>0.05). Severe complications occurred in 28 patients during hospitalization, and the incidence of complications was the highest in the hybrid Ⅳb technique group ( P<0.01). During follow-up, 4 patients died in the bypass group, 6 died in the external window group, and 8 died in the chimney group, with no significant difference ( P>0.05). Conclusions:The safety and efficacy of the left subclavian artery flow reconstruction by in vitro fenestration and chimney technique were similar. The occurrences of early complications were lower than that of the hybrid Ⅳb technique, but the reintervention rate of endoleak was higher.

Objective To analyze the stresses in implanted titanium solid and bone trabecular prosthesis hip replacements.Methods A femur model was built inversely based on Mimics software,and optimized using Geomagic software,and then materialized by SolidWorks software.The osteotomized femur was assembled with the metal femoral stem to form a model,and then the model was imported into ABAQUS for finite element calculation.The upper femur was divided into four regions in different states of integration:medial proximal point(small trochanter region),lateral proximal region(large trochanter region),proximal point of the femoral stem(region around the mid-portion of the styloid process)and distal region(around the end of the styloid process and distal portion).Calculations were carried out over the femoral stresses before and after implantation of titanium solid and trabecular prostheses under gait and stair-climbing loads and the interfacial stresses when the region was unintegrated.The type of deformation at the bone interface was analyzed by means of a stress ellipsoid.Results At the small trochanter region,the stress shielding rates of the trabecular prosthesis under gait and stair climbing loads were reduced by 20.5％and 14.7％compared to the titanium solid prosthesis,respectively.In case of different integration states of the titanium solid prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 10.842 MPa and 12.900 MPa,and the shear stresses reached 7.050 MPa and 6.805 MPa,respectively;in case of different integration states of the trabecular prosthesis,the interface tensile stresses under the gait and stair climbing loads were up to 3.858 MPa and 4.389 MPa,and the shear stresses reached 4.156 MPa and 3.854 MPa,respectively.Under the 2 different loads,the inboard shear stress ellipsoid of the interface opened toward the sides and the bone interface showed tensile deformation;the outboard shear stress ellipsoid of the interface opened up and down and had compressive deformation.Conclusion After total hip arthroplasty,the overall performance of the trabecular prosthesis is better than that of the titanium solid prosthesis.The unintegrated edges of the prosthesis-bone interface are susceptible to stress concentrations and distortion which may result in occurrence of failures.[Chinese Medical Equipment Journal,2024,45(3):29-35]

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

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.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.