With the application of FOLFOX regimen (oxaliplatin, fluorouracil, and leucovorin) in hepatic arterial perfusion (HAIC), chemotherapy has shown a higher value in the comprehensive treatment of hepatocellular carcinoma. Especially in the era of integration of targeted therapy and immunotherapy, the FOLFOX-HAIC, combined with immunotherapy and targeted therapy, further improves antitumor effect. The FOLFOX systemic chemotherapy combined with immunotherapy and targeted therapy scheme explored by the authors has achieved similar effects to triple therapy. Advanced hepatocellular carcinoma exhibits systemic disease characteristics, and systemic chemotherapy combined with targeted and immunotherapy has achieved higher disease control rates in the initial exploration. The mechanism may be that systemic chemotherapy changes the overall immune micro-environment of tumors, transforming the immune microenvironment from immunosuppressive to immune supportive, thereby better enhancing the efficacy of immunotherapy. The optimal regimen of systemic chemotherapy in comprehensive treatment may be obtained from the phase 3 study and basic studies in the future, which will be more efficient, safe and economical in the treatment of advanced hepatocellular carcinoma.

Objective:To investigate the efficacy of mFOLFOX7 regimen systemic chemo-therapy combined with camrelizumab and apatinib for hepatocellular carcinoma (HCC) with Vp4 portal vain tumor thrombus (PVTT).Methods:The single-arm, open, exploratory clinical study was conducted. The clinicopathological data of 15 HCC patients with Vp4 PVTT who were admitted to the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from April 2021 to October 2023 were collected. There were 14 males and 1 female, aged 48(range, 33-67)years. All patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. Observa-tion indicators: (1) clinical efficacy; (2) survival of patients. Measurement data with skewed distribution were represented as M(rang), and count data were described as absolute numbers or percentages. Results:(1) Clinical efficacy. All 15 patients underwent treatment with mFOLFOX7 regimen combined with camrelizumab and apatinib. According to the response evaluation criteria in solid tumors version 1.1, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 10/15, 1/15, 9/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. According to the modified response evaluation criteria in solid tumors, the ratio of objective response, ratio of complete response, ratio of partial response, ratio of disease control, median progression free survival time and median total survival time of the 15 patients were 12/15, 6/15, 6/15, 15/15, not reached and not reached. The median progression free survival time and median total survival time were both >9 months. Of the 15 patients, 7 cases were successfully treated with conversion therapy with the surgical conversion rate as 7/15, and all of them achieved R 0 resection. The other 6 cases were failed in conversion therapy, and there were 2 cases still undergoing conversion therapy. Of the 7 patients with successful conver-sion therapy, 5 cases achieved complete pathological remission, 1 case achieved major pathological remission with 90% of tumor tissue necrosis, and 1 case achieved complete remission through imaging examination, but new liver lesions appeared in multiple locations during further observation which were surgically removed. Results of histopathology examination on the patient confirmed multiple liver metastases. The proportion of treatment-associated adverse reactions in 15 patients was 13/15, with 7/15 having ≥grade 3 adverse reactions, including diarrhea (3/15), neutropenia (2/15), thrombo-cytopenia (2/15), and elevated aspartate aminotransferase (2/15). One patient may experience ≥1 adverse reaction. All patients were improved after symptomatic treatment. (2) Survival of patients. All 15 patients were followed up for 13.0(range, 2.0-31.0)months. During the follow-up period, 3 patients died. One case died of upper gastrointestinal bleeding after achieving partial remission, with a survival time of 7.5 months. One case died of multiple liver metastases of tumor, with tumors accounting for over 70% volume of liver and a survival time of 9.5 months. One case with multiple liver tumors and bilateral lung metastasis died due to disease progression after achieving partial remission, with a survival time of 13.5 months. The postoperative follow-up time for 7 patients undergoing surgical treatment was 14.0(range, 2.0-25.0)months. Of the 7 patients, 1 case experien-ced tumor recurrence 20.0 months after surgery, and 6 cases had no recurrence at last time of the follow-up (3 cases completed treatment and entered follow-up observation). The longest survival time was 31.0 months. Conclusion:The mFOLFOX7 regimen systemic chemotherapy combined with camrelizumab and apatinib for HCC with Vp4 PVTT is safe and feasible.

With the unremitting efforts of hepatobiliary surgeons,from wedge resection to anatomical resection,laparoscopic liver surgery has made rapid progress in theory and technical practice.However,due to the considerable technical challenges of laparoscopic liver resection(LLR),how to achieve standardized promotion and high-quality dissemination remains a difficult point for LLR at present.This paper discusses the key points of the quality control system for LLR,and systematically explains the current key points of LLR,providing reference basis for the standardization and popularization of laparoscopic hepatectomy.

Due to the inherent disease characteristics and surgical difficulties, the develop-ment of minimally invasive surgery in biliary tract cancer has encountered more difficulties and controversies. As one of the representative fields of modern precise surgery and an important part of multidisciplinary therapy, the value and application of minimally invasive surgery in the treatment of biliary tract cancer need to be further elaborated and standardized. Minimally invasive surgical techniques should be explored and studied under reasonable norms and supervision. More higher level evidence-based evidences should be obtained under the premise of ensuring the ethical prin-ciple of maximum benefit to patients, and ultimately promote the overall progress in the field.

SARS-CoV-2 infection causes complicated clinical manifestations with variable multi-organ injuries, however, the underlying mechanism, in particular immune responses in different organs, remains elusive. In this study, comprehensive transcriptomic alterations of 14 tissues from rhesus macaque infected with SARS-CoV-2 were analyzed. Compared to normal controls, SARS-CoV-2 infection resulted in dysregulation of genes involving diverse functions in various examined tissues/organs, with drastic transcriptomic changes in cerebral cortex and right ventricle. Intriguingly, cerebral cortex exhibited a hyperinflammatory state evidenced by significant upregulation of inflammation response-related genes. Meanwhile, expressions of coagulation, angiogenesis and fibrosis factors were also up-regulated in cerebral cortex. Based on our findings, neuropilin 1 (NRP1), a receptor of SARS-CoV-2, was significantly elevated in cerebral cortex post infection, accompanied by active immune response releasing inflammatory factors and signal transmission among tissues, which enhanced infection of the central nervous system (CNS) in a positive feedback way, leading to viral encephalitis. Overall, our study depicts a multi-tissue/organ transcriptomic landscapes of rhesus macaque with early infection of SARS-CoV-2, and provides important insights into the mechanistic basis for COVID-19-associated clinical complications.
Animals ; COVID-19/genetics* ; Macaca mulatta ; SARS-CoV-2/genetics* ; Transcriptome

Comprehensive treatment of biliary tract cancer has evolved rapidly, thereby improving disease control and long-term survival. The authors focus on the update of this emerging field and its impacts on surgical treatment to explore the development of surgery in the treatment of biliary tract cancer in the future. With the goal of medium- and long-term benefits, a comprehensive treat-ment based on multidisciplinary team and surgery-centered approach is recommended throughout treatment of biliary tract cancer. In the era of multidesciplinary team, surgical treatment of biliary tract cancer will develop toward precision, limited surgical scope, and minimally invasive technique.

Anatomic resection aims to improve the surgical efficacy of hepatocellular carcinoma by systematic resection of portal territory. However, due to its deviation of traditional theory and practice, the oncology effect is questionable. Anatomic resection based on portal territory(PT-AR) is planned by the analysis of real portal vein territory, and performed complete resection of tumor-bearing portal territory by fluorescent guidance, while exposing typical inter-territory hepatic vein, so as to ensure the complete function of future liver remnant. PT-AR is based on the core theory of classical anatomic resection, which will correct the deviation of traditional theory and practice from the technical level, so as to lead a better surgical oncology outcomes for hepatocellular carcinoma.

Objective:To establish neurodevelopmental mice model of schizophrenia(SZ) with prepulse inhibition(PPI) deficits and investigate the effectiveness of olanzapine on PPI disruption.Methods:On the 9th day of pregnancy of SPF grade C57BL/6 mice, female mice were injected with polyinosinic acid poly (I∶C) (6 mg/kg) through tail vein for immune stimulation. The stress model was constructed by chronic unpredictable mild stress 30-40 d after birth (PND30-40). The offspring mice were divided into pregnancy immune stimulation + adolescent stress group (P + S + group), pregnancy immune stimulation group (P + S- group), adolescent stress group (P-S+ group) and non stimulation group (P-S-group), with 18 mice in each group. The mice in P+ S+ group were divided into OLZ intervention group (OLZ group) and non-OLZ intervention group (non-OLZ group), with 9 mice in each group. The PPI function of mice was detected by acoustic startle reflex test after modeling and OLZ intervention. Adopt StatView Version 5.0 software for data analysis, and multi factors analysis of variance was used to test the main effect, interactive effect and simple effect of each factor.Results:The main effects of maternal Poly(I: C) immune activation and pubertal chronic unpredictable stress were significant( F(1, 330)=47.72, P<0.01), and there was a significant interaction between the two factors( F(1, 330)=14.80, P<0.01), simple effect analysis showed that average percent prepulse inhibition (PPI%) in P+ S+ group((15.42±6.13)%) was significantly decreased compared with groups of P+ S-((27.33±4.58)%), P-S+ ((31.17±3.97)%) and P-S-((47.14±12.28)%)(all P<0.01). There was significant gender difference in Prepulse inhibition(PPI)score( F(1, 396)=61.94, P<0.01), in male and female mice, average startle reactivity of Pulse under Prepulse+ Pulse influence of distinct intensities was significantly different( F(1, 198)=18.68, 18.44, P<0.01), and the maternal Poly(I∶C) immune activation had a significant main effect( F(1, 198)=32.18, 12.58, P<0.01) and interaction with pubertal chronic unpredictable stress( F(1, 198)=34.54, 11.39, P<0.01), simple effect analysis suggested that the average startle reactivity of Prepulse+ Pulse in P+ S+ group(0.47±0.12) was significantly higher than other three groups(P+ S-: 0.36±0.11, P-S+ : (0.25±0.22), P-S-: (0.31±0.19)) in male mice( P<0.01) and in P-S+ group was significantly higher than the other three groups in female mice ( P<0.01). OLZ treatment could efficiently reverse the deficits on PPI by increasing PPI%( F(1, 165)=18.24, P<0.01), OLZ could reduce PPI score in male "dual-hit" model mice( F(1, 102)=21.81, P<0.01)and raise it in female( F(1, 102)=4.88, P<0.05). Conclusion:OLZ can reverse PPI deficits in schizophrenic neurodevelopmental model mice, and in the evaluation of PPI function in the model mice through PPI of acoustic startle reflex, PPI% has better stability and reactivity to OLZ intervention.

Objective:To investigate the clinical efficacy of laparoscopic anatomical right posterior sector combined with anterior-dorsal segment resection for hepatocellular carcinoma.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 15 patients with hepatocellular carcinoma who underwent laparoscopic anatomical right posterior sector combined with anterior-dorsal segment resection in the Sun Yat-sen Memorial Hospital of Sun Yat-sen University from September 2020 to August 2021 were collected. There were 9 males and 6 females, aged 66(range, 35?77)years. Observation indicators: (1) surgical situations; (2) postoperative situations; (3) follow-up. Follow-up was conducted using outpatient examination and telephone interview to detect tumor recurrence and survival of patients in the postoperative 90 days. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers. Results:(1) Surgical situations. All the 15 patients underwent laparoscopic anatomical right posterior sector combined with anterior-dorsal segment resection successfully, without blood transfusion and conversion to laparotomy during the operation. The operation time, volume of intraoperative blood loss and occlusion time of first porta hepatis of the 15 patients were (155±17)minutes, (254±66)mL and (51±7)minutes, respectively. (2) Postoperative situations. The duration of postoperative hospital stay of the 15 patients was (7.4±2.1)days. Results of postoperative histopathological examination showed hepatocellular carcinoma and R 0 margins in all the 15 patients with a minimum distance from margin to tumor of (1.5±0.8)cm. There was none of the 15 patients transferred to intensive care unit, perioperative death or rehospitalization within 30 days after surgery. Of the 15 patients, 2 cases had postoperative complications, including 1 case with biliary fistula (grade Ⅰ of Clavien-Dindo classification) and 1 case with ascites (grade Ⅱ of Clavien-Dindo classification). Patients with complications were improved after washing and drainage, abdominal puncture and drainage. (3) Follow-up. All the 15 patients were followed up for the postoperative 90 days and none of them had tumor recurrence or death within postoperative 90 days. Conclusion:The laparoscopic anatomical right posterior sector and anterior-dorsal segment resec-tion for hepatocellular carcinoma is safe and feasible.

Colorectal cancer liver metastasis can be categorized as initially resectable and initially unresectable liver metastasis. Patients with initially resectable colorectal cancer liver metastases may benefit from hepatic surgery significantly,while those with initially unresectable metastases also have an opportunity to be treated radically by liver surgery after conversion therapy,so as to have a prolonged survival time. It is crucial to choose the right time and right way of surgical intervention. The timing depends on determination of tumor resectability,controlling of pre-operative systemic therapy and evaluation of liver function after systemic treatment. The selection of right way contains the election between synchronous operation and staged operation, resection margin and using of technologies such as laparoscope and associating liver partition and portal vein ligation for staged hepatectomy. This paper aims to explore the optimal timing for operation and the approaches of surgical method based on the research progress worldwide for prolonging the survival time of patients with colorectal cancer multiple liver metastases.