The identification and optimization of mutations in nanobodies are crucial for enhancing their therapeutic potential in disease prevention and control. However, this process is often complex and time-consuming, which limit its widespread application in practice. In this study, we developed a workflow, named Evolutionary-Nanobody (EvoNB), to predict key mutation sites of nanobodies by combining protein language models (PLMs) and molecular dynamic (MD) simulations. By fine-tuning the ESM2 model on a large-scale nanobody dataset, the ability of EvoNB to capture specific sequence features of nanobodies was significantly enhanced. The fine-tuned EvoNB model demonstrated higher predictive accuracy in the conserved framework and highly variable complementarity-determining regions of nanobodies. Additionally, we selected four widely representative nanobody-antigen complexes to verify the predicted effects of mutations. MD simulations analyzed the energy changes caused by these mutations to predict their impact on binding affinity to the targets. The results showed that multiple mutations screened by EvoNB significantly enhanced the binding affinity between nanobody and its target, further validating the potential of this workflow for designing and optimizing nanobody mutations. Additionally, sequence-based predictions are generally less dependent on structural absence, allowing them to be more easily integrated with tools for structural predictions, such as AlphaFold 3. Through mutation prediction and systematic analysis of key sites, we can quickly predict the most promising variants for experimental validation without relying on traditional evolutionary or selection processes. The EvoNB workflow provides an effective tool for the rapid optimization of nanobodies and facilitates the application of PLMs in the biomedical field.

Aldosterone synthetase deficiency (ASD) is a rare autosomal recessive genetic disorder caused by the CYP11B2 gene mutation.The clinical manifestations are mainly repeated vomiting, diarrhea, slow physical growth, hyponatremia, hyperkalemia, and hypovolemia in infants and young children.It is clinically difficult to distinguish it from other infantile salt loss diseases.At present, the diagnosis of ASD mainly depends on the measurement of steroid hormone levels and the analysis of genetic variants.9α-Fluhydrocortisone is the main drug for the treatment of ASD, but the treatment regimens are not yet unified.This article reviews the research progress in the etiology, pathogenesis, clinical phenotype, diagnosis and treatment of ASD in order to improve clinicians′ competence in diagnosing and treating this disease.

The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.

Purpose To explore the effect of compressed sensing(CS)technique with different acceleration factors on the quality of cardiac magnetic resonance cine sequences and feasibility of clinical application.Materials and Methods From January to July 2021,40 healthy volunteers were prospectively recruited for cardiac magnetic resonance cine imaging in Hefei First People's Hospital.Four scan protocols of volunteers were designed:SENSE 2 and CS-cine sequences with acceleration factors of 3,4 and 8.The imaging slices include four chamber heart,short axis heart,left ventricular two chamber heart and three chamber heart.Subjective score of image quality,left ventricular cardiac function and 16-segment myocardial thickness of SENSE 2 and CS3,CS4 and CS8 were compared and analyzed.Results Taking SENSE 2 image as the standard score of 5,the scores of CS3 and CS4 were above 3,and the scores of CS8 were below 3.There was no significant difference between the scores of four chamber heart and short axis heart images of CS3 and SENSE 2 sequence(all P>0.05).There were statistically significant differences in the subjective scores of image quality between the left ventricular two chamber heart and three chamber heart groups of each sequence(all P<0.05).There was no statistically significant difference in left ventricular function(left ventricular ejection fraction,left ventricular end systolic volume,left ventricular end diastolic volume,left ventricular stroke volume,left ventricular end-diastolic mass)(F=0.027,0.182,0.057,0.140,0.545)and myocardial thickness(F=0.052-7.366)among the four imaging schemes(all P>0.05).Conclusion Cardiac cine based on compressed sensing technology have good application prospects.With the increase of acceleration factors,the scanning time gradually decreases,and the corresponding image quality will also decrease.When the acceleration factor is 4,that is,the scanning time of the conventional cine sequence is reduced by 50%,the left ventricular function and myocardial thickness can still be accurately measured,and the image quality basically meets the diagnostic requirements.

Objective To investigate the effect of ultrasound-guided transverse abdominal plane block(TAPB)on pain inhibition and stress response in patients undergoing laparoscopic sleeve gastrectomy(LSG).Methods 98 cases of laparoscopic sleeve Gastrectomy patients admitted from March 2021 to October 2022 were selected as the research object,and they were randomly divided into control group(49 cases)and observation group(49 cases)by double blind method.The control group received general anesthesia,and the observation group received TAPB+general anesthesia.The postoperative pain,analgesic dosage,stress level,hemodynamics and adverse reactions of the two groups were compared.Results The dosage of sufentanil and propofol in the observation group,as well as the effective press frequency of the intravenous analgesia pump 48 hours after surgery[(232.38±29.62)μg,(328.40± 40.68)mg and(5.60±1.25)],were lower than those in the control group[(294.07±35.88)μg,(402.25±46.74)mg and(9.75±2.40)](P＜0.05).The visual analogue scale(VAS)scores for each time period of the observation group were(2.43±0.49),(2.29±0.46),(2.85±0.49),(2.41± 0.39),(2.12±0.41)and(1.82±0.32),respectivly.While,the control group were(2.95±0.46),(3.22±0.51),(3.92±0.47),(3.13±0.65),(2.83±0.57)and(2.05±0.53),respectivly.The difference between the two groups was statistically significant(P＜0.05).At the time of tracheal intubation(T2),at the end of operation(T3),and at the time of leaving the anesthesia recovery room(T4),the fluctuation range of mean arterial pressure[86.00(79.00,94.00)mmHg,87.00(80.00,90.00)mmHg and 89.00(84.00,95.00)mmHg vs 82.00(75.00,90.00)mmHg,85.00(77.00,93.00)mmHg and 87.00(80.00,97.00)mmHg],heart rate[78.00(67.00,83.00)times/min,80.00(74.00,86.00)times/min and 81.00(76.00,90.00)times/min vs 78.00(67.00,83.00)times/min,80.00(74.00,86.00)times/min and 81.00(76.00,90.00)times/min]and blood oxygen saturation[97.38(97.00,97.75)％,98.69(98.30,99.05)％and 99.16(98.80,99.35)％vs 96.54(96.15,96.80)％,98.02(97.65,98.45)％and 98.73(98.43,99.15)％]in the observation group was significantly smaller than that of the control group(P＜0.05).In the observation group,cortisol levels were(192.47 ±40.25)ng/ml,(151.34±39.62)ng/ml and(118.69±30.57)ng/ml at 6 hours,24 hours and 48 hours,respectively,while in the control group were(206.24±45.34)ng/ml,(178.24±37.58)ng/ml and(143.63±32.34)ng/ml,respectively;C-reactive protein(CRP)in the observation group were(25.24±6.29)mg/L,(20.93±5.83)mg/L and(13.61±4.29)mg/L,respectively,while in the control group were(28.13±6.92)mg/L,(23.25±5.21)mg/L and(16.38±4.35)mg/L,respectively;interleukin-6(IL-6)in the observation group were(44.87±7.95)pg/L,(38.34±6.13)pg/L and(34.27±5.32)pg/L,respectively,while in the control group were(56.43±7.23)pg/L、(42.24±6.58)pg/L、(37.66±6.03)pg/L,respectively.The difference between the two groups was statistically significant(P＜0.05).The total incidence of adverse reactions of the observation group(4.08％)was lower in than that of the control group(20.41％)(P＜0.05).Conclusion Ultrasound-guided TAPB for LSG patients has a good effect on postoperative pain suppression,can reduce the stress response of the body after surgery,and is safe.

Objective:To investigate the expression and clinical significance of plasma methylated SEPT9 (mSEPT9) gene in patients with primary liver cancer.Methods:393 cases who visited our hospital from May 2016 to October 2018 were selected. Among them, 75 cases were in the primary liver cancer (PLC) group, 50 cases were in the liver cirrhosis (LC) group, and 268 cases were in the healthy control group (HC). The three groups' positive rates of mSEPT9 expression in the peripheral plasma were detected by the polymerase chain reaction (PCR) fluorescent probe method. The correlational clinical features of liver cancer were analyzed. At the same time, the electrochemiluminescence detection method was used to compare the AFP positive rate. Statistical analysis was conducted using chi-square tests or continuity-corrected chi-square tests.Results:367 cases actually had valid samples. There were 64, 42, and 64 cases in the liver cancer group, cirrhosis group, and healthy control group, respectively. Among them, 34 cases of liver cancer were verified from pathological tissues. The positive rate of plasma mSEPT9 was significantly higher in the liver cancer group than that in the liver cirrhosis and healthy control groups [76.6% (49/64), 35.7% (15/42), and 3.8% (10/261), respectively], and the differences were statistically significant ( χ2 = 176.017, P < 0.001). The sensitivity of plasma mSEPT9 detection (76.6%) was significantly better in liver cancer (76.6%) than that of AFP patients (54.7%), and the difference was statistically significant ( χ2 = 6.788, P < 0.01). Compared with the single detection, the sensitivity and specificity of plasma mSEPT9 combined with AFP were significantly improved (89.7% vs. 96.3%, respectively). Patients with liver cancer aged≥50 years, with clinical stage II or above, and those with pathological signs of moderate to low differentiation had higher levels of plasma mSEPT9 positive expression, and the differences were statistically significant ( χ2 = 6.41, 9.279, 6.332, P < 0.05). During the follow-up period, the survival time of liver cancer patients with positive plasma mSEPT9 expression was significantly shorter than that of those with negative expression (310 ± 26 days vs. 487 ± 59 days, respectively), with statistically significant differences (Log Rank P = 0.039). Conclusion:In China, the positive rate of plasma mSEPT9 detection in liver cancer patients is higher than that of AFP in relation to age, clinical stage, and degree of tissue differentiation; additionally, it has certain survival predictive values. As a result, detecting this gene has important clinical significance and potential clinical application value in the non-invasive diagnosis and prognosis assessment of patients with primary liver cancer.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

Traditional Chinese Medicine (TCM) has become an important part of the health system in the Sultanate of Oman. Although there is no independent law, the local health department has implemented the administrative measures such as the admittance assessment system of TCM doctors and the standardized examination and approval of TCM clinics. The development of TCM in the Sultanate of Oman is supported by the policies of the two governments, with the characteristics likemedical cooperation starting with high-level personnel, the cooperation in economy, trade and medical treatment, TCM and local traditional medicine showing inclusive with good base, and the advantages of TCM theory and treatment meeting the needs of the local medical market. The prospect of cooperation in TCM market is broad. It is suggested that the local government should promote the legislation of traditional medicine and improve the admittance system of practitioners. China needs to promote the formulation of international standards of TCM and optimize the cooperation platform of TCM by using Internet and other technologies. The practitioners in China need to carry out medical activities on the premise of understanding and respecting the local cultural background.In order to promote the development of TCM in Arab countries, the Sultanate of Oman will radiate the whole Middle East through the above strategies.

Once an abdominal aortic graft infection occurs,it is often catastrophic associated without high morbidity and mortality.Standard surgical treatment includes removing infected grafts,arteries,and surrounding tissues,and revascularization of blood supply to organs and limbs. Extra-anatomical vascular bypass and in-situ reconstruction are the main surgical treatment methods,and many factors affect the prognosis of surgical treatment. So far,there are a variety of vascular grafts used to restore revascularization in clinical practice,mainly including rifampicin or silver-coated artificial blood vessels,autologous veins,cryopreserved allogeneic blood vessels,or bovine pericardium and other biological materials. There is no consensus on the selection of the best vascular graft. In recent years,clinical application studies have confirmed that the results of cryopreserved allogeneic blood vessels for the treatment of graft infectious diseases are acceptable,but the complications related to grafts should not be ignored. This article reviews the clinical application progress of cryopreserved allogeneic blood vessels for the treatment of abdominal aortic graft infection.

Once an abdominal aortic graft infection occurs,it is often catastrophic associated without high morbidity and mortality.Standard surgical treatment includes removing infected grafts,arteries,and surrounding tissues,and revascularization of blood supply to organs and limbs. Extra-anatomical vascular bypass and in-situ reconstruction are the main surgical treatment methods,and many factors affect the prognosis of surgical treatment. So far,there are a variety of vascular grafts used to restore revascularization in clinical practice,mainly including rifampicin or silver-coated artificial blood vessels,autologous veins,cryopreserved allogeneic blood vessels,or bovine pericardium and other biological materials. There is no consensus on the selection of the best vascular graft. In recent years,clinical application studies have confirmed that the results of cryopreserved allogeneic blood vessels for the treatment of graft infectious diseases are acceptable,but the complications related to grafts should not be ignored. This article reviews the clinical application progress of cryopreserved allogeneic blood vessels for the treatment of abdominal aortic graft infection.