Hepatocellular carcinoma(HCC)is one of the most common malignancies with high morbidity and mortality rates worldwide.With the advances in molecular biology and tumor immunology,molecular-targeted agents represented by tyrosine kinase inhibitors(such as sorafenib and lenvatinib)and immunotherapy represented by PD-1/PD-L1 monoclonal antibodies have brought hope for patients with advanced HCC.The combination of immunotherapy and anti-angiogenic therapy can further improve the treatment outcome of patients.In addition,the optimization and integration of stereotactic body radiotherapy,local treatment,and systemic treatment may maximize the benefits of patients.In the future,through a deep understanding of the heterogeneity of HCC,the development of precision molecular subtyping and individualized treatment,and the establishment of a multidisciplinary collaborative diagnosis and treatment system,systemic therapy is expected to achieve long-term management of advanced HCC.This article reviews the current status and advances in systemic therapy for advanced HCC.

Biliary tract carcinoma （BTC） is a type of gastrointestinal tumor with a low incidence rate and a strong invasive ability， mainly including intrahepatic cholangiocarcinoma （ICC）， extrahepatic cholangiocarcinoma （ECC）， and gallbladder carcinoma （GC）， often accompanied by local progression or distant metastasis. Surgery is often the preferred treatment method for patients with local resectable tumor； however， there is still a high risk of recurrence after radical surgery. Therefore， multiple treatment modalities are often required for BTC patients， including surgical resection， systemic treatment （such as targeted therapy， chemotherapy， and immunotherapy）， and/or a combination of local treatment methods. With the development of the field of BTC， it is critical for surgical oncologists to understand and master the latest surgical strategies and the best patient selection and management systems. In view of the complexity of treatment and the continuous development of diagnosis and treatment techniques， Annals of Surgical Oncology， an authoritative American journal of cancer surgery， recently published the practical diagnosis and treatment guidelines for hepatobiliary tumors， including hepatocellular carcinoma （HCC）， ICC， ECC， and GC， aiming to provide more evidence-based evidence for the clinical management and decision-making of patients with hepatobiliary tumors. Due to the limitations of length and different emphases， this article mainly introduces the recommendations for the evaluation points and clinical treatment of ECC and GC in the guidelines， so as to provide a reference for clinical practice.

Objective:Rejection remains the most important factor limiting the survival of transplanted kidneys.Although a pathological biopsy of the transplanted kidney is the gold standard for diagnosing rejection,its limitations prevent it from being used as a routine monitoring method.Recently,peripheral blood lymphocyte subpopulation testing has become an important means of assessing the body's immune system,however,its application value and strategy in the field of kidney transplantation need further exploration.Additionally,the development and utilization of routine test parameters are also important methods for exploring diagnostic strategies and predictive models for kidney transplant diseases.This study aims to explore the correlation between peripheral blood lymphocyte subpopulations and T cell-mediated rejection(TCMR)and antibody-mediated rejection(ABMR),as well as their diagnostic value,in conjunction with routine blood tests. Methods:A total of 154 kidney transplant recipients,who met the inclusion and exclusion criteria and were treated at the Second Xiangya Hospital of Central South University from January to December,2021,were selected as the study subjects.They were assigned into a stable group,a TCMR group,and an ABMR group,based on the occurrence and type of rejection.The basic and clinical data of these recipients were retrospectively analyzed and compared among the 3 groups.The transplant kidney function,routine blood tests,and peripheral blood lymphocyte subpopulation data of the TCMR group and the ABMR group before rejection treatment were compared with those of the stable group. Results:The stable,TCMR group,and ABMR group showed no statistically significant differences in immunosuppressive maintenance regimens or sources of transplanted kidneys(all P>0.05).However,the post-transplant duration was significantly longer in the ABMR group compared with the stable group(P<0.001)and the TCMR group(P<0.05).Regarding kidney function,serum creatinine levels in the ABMR group were higher than in the stable group and the TCMR group(both P<0.01),with the TCMR group also showing higher levels than the stable group(P<0.01).Both TCMR and ABMR groups had significantly higher blood urea nitrogen levels than the stable group(P<0.01),with no statistically significant difference between TCMR and ABMR groups(P>0.05).The estimated glomerular filtration rate(eGFR)was lower in both TCMR and ABMR groups compared with the stable group(both P<0.01).In routine blood tests,the ABMR group had lower hemoglobin,red blood cell count,and platelet count than the stable group(all P<0.05).The TCMR group had higher neutrophil percentage(P<0.05)and count(P<0.05)than the stable group,and the ABMR group had a higher neutrophil percentage than the stable group(P<0.05).The eosinophil percentage and count in the TCMR group were lower than in the stable and ABMR groups(all P<0.05).Both TCMR and ABMR groups had lower basophil percentage and count,as well as lower lymphocyte percentage and count,compared with the stable group(all P<0.05).There were no significant differences in monocyte percentage and count among the 3 groups(all P>0.05).In lymphocyte subpopulations,the TCMR and ABMR groups had lower counts of CD45+cells and T cells compared with the stable group(all P<0.05).The TCMR group also had lower counts of CD4+T cells,NK cells,and B cells than the stable group(all P<0.05).There were no significant differences in the T cell percentage,CD4+T cell percentage,CD8+T cell percentage and their counts,CD4+/CD8+T cell ratio,NK cell percentage,and B cell percentage among the stable,TCMR,and ABMR groups(all P>0.05). Conclusion:The occurrence of rejection leads to impaired transplant kidney function,accompanied by characteristic changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations in kidney transplant recipients.The different characteristics of changes in some parameters of routine blood tests and peripheral blood lymphocyte subpopulations during TCMR and ABMR may help predict and diagnose rejection and differentiate between TCMR and ABMR.

Objective:To observe the clinical efficacy of mouse nerve growth factor (mNGF) combined with rehabilitation on children with global developmental delay(GDD).Methods:It was a prospective multicenter clinical randomized controlled trial (RCT) involving 120 children with GDD admitted to 5 hospitals in China from May 2020 to January 2022.They were randomly divided into mNGF group and conventional rehabilitation group using block randomization method.All children were managed by standardized rehabilitation after recruitment, and those in the mNGF group were additionally given mNGF injections.All subjects were surveyed using the Gesell Development Diagnosis Schedules(GDDS) at baseline, 90 days and 120 days after treatment, and their developmental quotient (DQ) was recorded.Clinical efficacy was analyzed by the paired t-test, rank sum test and Chi- squared test. Results:After 90 days of treatment and the continuous follow-up to 120 days, the increases in the DQ of gross motor (7.520±13.900 vs.0.450±11.459), fine motor (7.800±15.346 vs.1.250±11.581), adaptive behavior (7.730±13.428 vs.2.100±12.022) and personal-social behavior (6.780±11.651 vs.1.780±10.120) than baseline were significantly higher in mNGF group than those of conventional rehabilitation group (all P<0.05). Serious adverse events and important drug-related medical events were not reported. Conclusions:mNGF combined with rehabilitation effectively enhances the development levels of gross motor, fine motor, adaptive behavior and personal-social behavior, and continuously improves the condition of GDD in children with a high safety.

Hepatocellular carcinoma (HCC) is the most common primary hepatic malign-ancy in clinic. The prognosis of patients remains extremely poor because of the high malignancy and easy recurrence and metastasis of HCC. In recent years, the roles of platelets in promoting the malignant progression of HCC have increasingly attracted much attention. It is known that platelets could promote HCC cells proliferation and invasion through tumor microenvironment. On the other hand, platelets are capable to promote HCC cells distant metastasis by facilitating tumor cells evasion of immune surveillance. Besides, the platelet-derived growth factors and proangiogenic factors are also involved in the proliferation, invasiveness, and neovascularization of HCC. In addition, patients with HCC normally have a background of cirrhosis, and it is still controversial that whether the thrombocytopenia by portal hypertension and hypersplenism can promote the malignant progress of HCC. In view of this, the diagnostic and prognostic value of platelet levels, as well as platelet-associated scores in HCC have increasingly become research focus. The authors elaborate the detailed mechanisms of platelets in malignant progression of HCC, and discuss the recent research progress of platelets as effective diagnostic or prognostic tools for the assessment of HCC, which is of great importance to optimize the current treatment regimen and explore novel therapeutic strategies against HCC.

MicroRNA-132 (miR-132), a small RNA that regulates gene expression, is known to promote neurogenesis in the embryonic nervous system and adult brain. Although exposure to psychoactive substances can increase miR-132 expression in cultured neural stem cells (NSCs) and the adult brain of rodents, little is known about its role in opioid addiction. So, we set out to determine the effect of miR-132 on differentiation of the NSCs and whether this effect is involved in opioid addiction using the rat morphine self-administration (MSA) model. We found that miR-132 overexpression enhanced the differentiation of NSCs in vivo and in vitro. Similarly, specific overexpression of miR-132 in NSCs of the adult hippocampal dentate gyrus (DG) during the acquisition stage of MSA potentiated morphine-seeking behavior. These findings indicate that miR-132 is involved in opioid addiction, probably by promoting the differentiation of NSCs in the adult DG.
Animals ; Cell Differentiation ; Cell Line, Tumor ; Dentate Gyrus ; metabolism ; Gene Expression Regulation ; Male ; MicroRNAs ; metabolism ; Neural Stem Cells ; metabolism ; Opioid-Related Disorders ; metabolism ; Rats, Sprague-Dawley

Objective To investigate the shaping rules of the femoral heads in the morphological perspective.The research objects are hips of normal children and children who have developmental dysplasia of the hip(DDH) and after closed reduction or limited open reduction.At the same time measuring and analyzing normal hip femoral head form changing with the children's age.Methods Collecting the DDH cases that after closed reduction and limited open reduction from June 2013 to December 2015.The follow-up period was more than 1 year.MRI images were collected before surgery,6 months after surgery,1 year after surgery,and 2 years after surgery.In addition,normal hip joint MRI images from 0 to 18 years old were collected for controlled study.Descriptive data on the affected side,healthy side and normal hip joint morphology of the hip dislocation were statistically analyzed.Results (1) The mean eccentricity of femoral head in normal hip decreased from (0.362 ±0.069) at 1-2 years to(0.141 ±0.028) at 18-19 years.(2) The eccentricity of femoral head before closed reduction and limited open reduction were both greater than those of healthy side.There was no significant difference in the eccentricity of the femoral head between the healthy side and the affected side at 1 year after closed reduction (P =0.211).There was no significant difference in the diameter of the bilateral femoral heads (P =0.871).The eccentricity of the bilateral femoral heads remained different at 2 years after limited open reduction (P =0.028),and the diameter of the affected femoral head exceeded the healthy side 1 year after surgery (P =0.001).Conclusion The shape of the femoral head of normal children gradually approaches the spherical shape with age.One year after closed reduction of DDH,the shape and size of the affected femoral head are close to the healthy side,and the femoral head of the affected side increases more than the healthy side in 1 ～ 2 years after open reduction and the morphology is still different.

Objective To study the interactions between the highly pathogenic avian influenza H5N1 nucleoprotein (H5N1 NP) and NF-κB-inducing kinase (NIK),and to reveal the effect of H5N1 NP on NIK-induced NF-κB transcriptional activity.Methods The gene encoding NIK protein was amplified by RT-PCR from total RNA of HeLa cell line.Eukaryotic expression plasmid pCMV-Myc-NIK and prokaryotic expression plasmid pGEX-4T-1-NP (GST-NP) were constructed by cloning from HeLa cell cDNA and pcDNA3-Flag-NP vector,respectively.Co-immunoprecipitation (co-IP) and GST pull-down were used to test the interactions between H5N1 NP and NIK.Dual-luciferase reporter gene analysis system was used to test the effect of H5N1 NP on NIK-induced NF-κB transcriptional activity.Results Co-IP and GST pull-down showed that pCMV-Myc-NIK and pGEX-4T-1-NP (GST-NP) could express Myc tagged NIK protein and GST tagged NP protein in HEK293T cells and E.coli,respectively,and that H5N1 NP was associated with NIK in vivo and in vitro.Dual-luciferase reporter gene analysis suggested that H5N1 could inhibit NIK-induced NF-κB transcriptional activity.Conclusion H5N1 NP interacts with NIK and inhibits NIK-induced NF-κB transcriptional activity.This finding can facilitate further study of H5N1.

Objective To observe the effects of different levels of stroke volume variation (SVV)directed fluid therapy on prognosis in elderly patients.Methods One hundred and ten patients (male 67 cases,female 43 cases,aged 65-80 years,ASA grade Ⅰ or Ⅱ)undergoing abdominal sur-geries were randomized into three groups on the basis of SVV level:1 1%≤SVV≤14% (group H,n=37),7%≤SVV≤10% (group M,n = 37),3% ≤ SVV≤ 6% (group L,n = 36).Each group ac-cepted different fluid therapy strategy.Perioperative intake and outtake volume were recorded.Progno-sis indicators included gastrointestinal function recovery,post and total length of hospital stay and so on were collected.Postoperative complications were also recorded.Results Along with the level of SVV dropped,The volume of colloid and crystalloid among groups were significantly increased (P <0.05).There were no remarkable difference in the time interval of activity off bed,liquid diet,gastrointestinal decompres-sion and catheterization.Group L had a delayed exhaust time compared with group H (P <0.05).Patients in the group M had a shorter time to have semi-liquid diet.The transition of diet was also shortest in the group M.But these differences were not statistically significant.The group M also had a shorter time in first-degree or above nursing time and post and total length of hospital stay compared with group L (P <0.05).The incidence of postoperative infection in group L was higher than other two groups.Incidence of anastomosis leakage in group H was higher than that in other two groups (P <0.05).Conditions of compli-cations in group L were more severe and complicated compared with other two groups.Conclusion 3%≤SVV≤6% may increase the risk of postoperative infection and prolong the time of hospitalization.Patients in the level of 7%≤SVV≤10% may have a better postoperative recovery.This level could be a better goal of perioperative fluid therapy in elderly patients.

Purpose To investigate the expression of insulin-like growth factorIImRNA binding protein 3 ( IMP3 ) and microvessel density (MVD) in squamous carcinoma of the cervix (SCC) and analysis their relationship in SCC. Methods The expression of IMP3 and MVD was examined by immunohistochemistry SP method in normal cervical epithelium ( NCE) , low-grade cervical intraepi-thelial neoplasia (CIN-L), high-grade cervical intraepithelial neoplasia (CIN-H) and SCC. Results (1)The positive expression rates of IMP3 in NCE, CIN-L, CIN-H, SCC tissues were 0(0/15), 0(0/11), 37.5%(9/24) and 86.0%(43/50), the difference was statistically significant (x 2 =53.345, P=0.000). IMP3 expression was significant difference among NCE and CIN-H, SCC (P<0.008 3), and that was also among SCC and CIN-L, CIN-H (P<0.008 3). (2)The MVD count was increased with the development of cervical squamous lesion, there was significant difference among those groups (F=145.968, P<0.01), and the difference was al-so statistically significant between every two groups (P<0.05). The positive expression of IMP3 and MVD count in 50 cases of SCC tissues showed statistical difference in different pathologic grade, lymph node metastasis, and depth of tumor invasion groups ( P<0.05), but didn't in different patients’age groups (P>0.05). And the positive expression of IMP3 was closely related with MVD count in SCC tissues (rs =0.323, P<0.05). Conclusion IMP3 plays an important role in the occurrence, infiltration and metasta-sis of SCC, and the abnormal expression of IMP3 may relate with the angiogenesis of tumors.