Objective To explore the technical process and clinical application of laparoscopic combined upper midline incision minimally invasive liver transplantation. Methods A retrospective analysis was conducted on 30 cases of laparoscopic combined upper midline incision minimally invasive liver transplantation. The cases were divided into cirrhosis group (15 cases) and liver failure group (15 cases) based on the primary disease. The surgical and postoperative conditions of the two groups were compared. Results All patients successfully underwent laparoscopic "clockwise" liver resection, with no cases of passive conversion to open surgery or intolerance to pneumoperitoneum. In 6 cases, the right lobe was relatively large, and the right hepatic ligaments could not be completely mobilized. One case required an additional reverse "L" incision during open surgery. All patients successfully completed the liver transplantation, with no major intraoperative bleeding, cardiovascular events, or other occurrences in the 30 patients. The model for end-stage liver disease (MELD) score in the cirrhosis group was lower than that in the liver failure group (P<0.001). There were no statistically significant differences between the two groups in terms of age, surgical time, blood loss, anhepatic phase, or cold ischemia time (all P>0.05). During the perioperative period, there was 1 case of hepatic artery embolism, 1 case of portal vein anastomotic stenosis, no complications of hepatic vein and inferior vena cava, and 3 cases of biliary anastomotic stenosis, all of which occurred in the liver failure group. Conclusions In strictly selected cases, the minimally invasive liver transplantation technique combining laparoscopic hepatectomy with upper midline incision for graft implantation has the advantages of smaller incisions, less bleeding, relatively easier operation, and faster postoperative recovery, which is worthy of clinical promotion and application.

Objective To explore the feasibility and clinical experience of the middle hepatic vein splitting-reconstruction technique in split liver transplantation from low-age donor livers. Methods A retrospective analysis was conducted on the cases of two low-age donor livers that underwent middle hepatic vein splitting-reconstruction, which were transplanted into four child recipients at the Liver Transplantation Center of the Third Affiliated Hospital of Sun Yat-sen University from January 2017 to July 2023. The surgical and postoperative conditions were summarized and analyzed. Results Donor 1 was a 6-year-old and 4-month-old girl with a body weight of 21 kg, and the obtained donor liver weighed 496 g. After splitting, the left and right liver weights were 201 g and 280 g, and transplanted into a 9-month-old boy weighing 6.5 kg and a 9-month-old boy weighing 7.5 kg, respectively. The graft to recipient weight ratio (GRWR) was 3.09% and 3.73%, respectively. Donor 2 was a 5-year-old and 8-month-old boy with a body weight of 19 kg, and the donor liver weighed 673 g. After splitting, the left and right liver weights were 230 g and 400 g, and transplanted into a 13-month-old girl weighing 9.5 kg and a 15-month-old boy weighing 12 kg. The GRWR was 2.42% and 3.33%, respectively. Both donor livers were split ex vivo, with the middle hepatic vein being completely split in the middle and reconstructed using allogeneic iliac vein and iliac artery vascular patches. According to GRWR, none of the 4 transplant livers were reduced in volume. Among the 4 recipients, one died due to postoperative portal vein thrombosis and non-function of the transplant liver, while the other three cases recovered smoothly without early or late complications. Regular follow-up was conducted until July 31, 2023, and liver function recovered well. Conclusions Under the premise of detailed assessment of the donor liver and meticulous intraoperative operation, as well as matching with suitable child recipients, low-age donor livers may be selected for splitting. The complete splitting and reconstruction of the middle hepatic vein in the middle may effectively ensure the adequate venous return of the left and right liver and provide sufficient functional liver volume.

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

The pharmaceutical industry faces challenges in quality digitization for complex multi-stage processes, especially in small-sample systems. Here, an intelligent quality prediction and diagnostic (IQPD) framework was developed and applied to Tong Ren Tang's Niuhuang Qingxin Pills, utilizing four years of data collected from four production units, covering the entire process from raw materials to finished products. In this framework, a novel path-enhanced double ensemble quality prediction model (PeDGAT) is proposed, which combines a graph attention network and path information to encode inter-unit long-range and sequential dependencies. Additionally, the double ensemble strategy enhances model stability in small samples. Compared to global traditional models, PeDGAT achieves state-of-the-art results, with an average improvement of 13.18% and 87.67% in prediction accuracy and stability on three indicators. Additionally, a more in-depth diagnostic model leveraging grey correlation analysis and expert knowledge reduces reliance on large samples, offering a panoramic view of attribute relationships across units and improving process transparency. Finally, the IQPD framework integrates into a Human-Cyber-Physical system, enabling faster decision-making and real-time quality adjustments for Tong Ren Tang's Niuhuang Qingxin Pills, a product with annual sales exceeding 100 million CNY. This facilitates the transition from experience-driven to data-driven manufacturing.

Objective:To investigate the anatomic classification and reconstruction of right intrahepatic bile duct in the donor liver of split liver transplantation (SLT).Methods:The retrospective and descriptive study was constructed. The clinical data of 85 patients who underwent SLT in the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to January 2022 were collected. There were 65 males and 20 females, aged 45(range, 1-82)years. Observation indicators: (1) surgical conditions; (2) anatomy of right intrahepatic bile duct; (3) bile duct reconstruction; (4) postoperative biliary complications; (5) follow-up. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) or M( Q1, Q3).Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Surgical conditions. Of the 85 donor livers, 11 donor livers were split between the left and right hemilivers, and 74 donor livers were split between the classic right trilobe and left lateral lobe. The cold ischemia time of 85 donor livers was 291(273, 354)minutes, and the operation time, anhepatic phase time and volume of intraoperative blood transfusion of 85 recipients were (497±97)minutes, 51(40, 80)minutes and 8(7, 12)U. (2) Anatomy of right intrahepatic bile duct. Of the 85 donor livers, there were 47 donor livers with classic bile duct anatomical model (type 1), of the ratio as 55.3%(47/85), and 38 donor livers with anatomical variants, of the ratio as 44.7%(38/85). Of the 38 donor livers with anatomical variants, 7 donor livers were type 2, 16 donor livers were type 3a, 2 donor livers were type 3b, 2 donor livers were type 3c, 1 donor liver was type 4, 3 donor livers were type 5a, 4 donor livers were type 5b, 3 donor livers were type 6. For bile duct splitting patterns of the 85 donor livers, 84 donor livers were split with the main trunk of common hepatic duct preserving in the right hemiliver or right trilobe, and 1 donor liver were treated with complete left and right hemiliver splitting to preserve the main trunk of the common hepatic duct in the left hemiliver and the right hemiliver in the right hepatic duct (type 1 bile duct anatomical model). There were 84 donor livers with only one bile duct opening, and 1 donor liver with two bile duct openings (type 3c bile duct anatomical model). (3) Bile duct reconstruction. Of the 85 recipients, there were 69 recipients with common bile duct end-to-end anastomosis to common bile duct of donor liver (38 donor livers with type 1 bile duct anatomical model, 5 donor livers with type 2 bile duct anatomical model, 14 donor livers with type 3a bile duct anatomical model, 2 donor livers with type 3b bile duct anatomical model, 1 donor liver with type 4 bile duct anatomical model, 3 donor livers with type 5a bile duct anatomical model, 4 donor livers with type 5b bile duct anatomical model, 2 donor livers with type 6 bile duct anatomical model), 11 recipients with jejunum anastomosis to common bile duct of donor liver (7 donor livers with type 1 bile duct anatomical model, 2 donor livers with type 2 bile duct anatomical model, 1 donor liver with type 3c bile duct anatomical model, 1 donor liver with type 6 bile duct anatomical model), 3 recipients with jejunum anastomosis to common hepatic duct of donor liver (1 donor liver with type 1 bile duct anatomical model, 2 donor livers with type 3a bile duct anatomical model), 1 recipient with jejunum anastomosis to right hepatic duct of donor liver (type 1 bile duct anatomical model), 1 recipient with common hepatic duct end-to-end anastomosis to right posterior branch of donor liver combined with jejunum of the recipient Roux-en-y anastomosis to common hepatic duct of donor liver (type 3c bile duct anatomical model). (4) Postoperative biliary complications. Of the 85 recipients, 6 cases had postoperative biliary complications, with an incidence of 7.1% (6/85). Of the 6 recipients with postoperative biliary complications, there were 5 recipients with donor liver with type 1 bile duct anatomical model, including 3 cases undergoing postoperative biliary stricture with biliary leakage and 2 cases undergoing postoperative biliary anastomotic stricture, 1 recipient with donor liver with type 3b bile duct anatomical model and undergoing postoperative biliary anastomotic stricture and bile leakage in the liver section. Cases with biliary complications were 5 in the 47 recipients with donor liver with classic bile duct anatomical model and 1 in the 38 recipients with donor liver with anato-mical variants, showing no significant difference between them ( P>0.05). (5) Follow-up. There were 83 recipients receiving followed up for 52(12,96)months. During the follow-up period, 2 recipients died due to non-biliary complication factors (1 donor liver with type 1 bile duct anatomical model and 1 donor liver with 3a bile duct anatomical model). Conclusion:The anatomical classification of right intrahepatic bile duct of donor liver in SLT is mainly classical bile duct anatomical model, and the bile duct reconstruction scheme is mainly common bile duct of donor liver end-to-end anasto-mosis to common bile duct of recipient.

Objective To investigate the diagnosis and treatment strategy of the portal vein complications in children undergoing split liver transplantation. Methods The clinical data of 88 pediatric recipients who underwent split liver transplantation were retrospectively analyzed. Intraoperative anastomosis at the bifurcating site of the portal vein or donor iliac vein bypass anastomosis was performed depending on the internal diameter and development of the recipient's portal vein. A normalized portal venous blood stream monitoring was performed during the perioperative stage. After operation, heparin sodium was used to bridge warfarin for anticoagulation therapy. After portal vein stenosis or thrombosis was identified with enhanced CT or portography, managements including embolectomy, systemic anticoagulation, interventional thrombus removal, balloon dilatation and/or stenting were performed. Results Among the 88 recipients, a total of 10 children were diagnosed with portal vein complications, of which 4 cases were diagnosed with portal vein stenosis at 1 d, 2 months, 8 months, and 11 months after surgery, and 6 cases were diagnosed with portal vein thrombosis at intraoperative, 2 d, 3 d (n=2), 6 d, and 11 months after surgery, respectively. One patient with portal vein stenosis and one patient with portal vein thrombosis died perioperatively. The fatality related to portal vein complications was 2% (2/88). Of the remaining 8 patients, 1 underwent systemic anticoagulation, 2 underwent portal venous embolectomy, 1 underwent interventional balloon dilatation, and 4 underwent interventional balloon dilatation plus stenting. No portal venous related symptoms were detected during postoperative long term follow up, and the retested portal venous blood stream parameters were normal. Conclusions The normalized intra- and post-operative portal venous blood stream monitoring is a useful tool for the early detection of portal vein complications, the early utilization of useful managements such as intraoperative portal venous embolectomy, interventional balloon dilatation and stenting may effectively treat the portal vein complications, thus minimizing the portal vein complication related graft loss and recipient death.

Objective To achieve automatic segmentation of cell nuclei in gastrointestinal cancer pathological images by using a deep learning algorithm,so as to assist in the quantitative analysis of subsequent pathological images.Methods A total of 59 patients with gastrointestinal cancer treated in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine from Jan 2022 to Feb 2022,were selected as the research objects.Python and LabelMe were used for data anonymization,image segmentation,and region of interest annotation of patients'pathological images.A total of 944 pathological images were included,and 9 703 nuclei were annotated.Then,a new semantic segmentation model based on deep learning was constructed.The model introduced deformable attention transformer(DAT)to realize automatic,accurate and efficient segmentation of pathological image nuclei.Finally,multiple segmentation evaluation criteria are used to evaluate the model's performance.Results The mean absolute error of the segmentation results of the model proposed in this paper was 0.112 6,and the dice coefficient(Dice)was 0.721 5.Its effect was significantly better than the U-net baseline model,and it was ahead of models such as ResU-net++,R2Unet and R2AttUnet.Moreover,the segmentation results were relatively stable with good generalization.Conclusion The segmentation model established in this study can accurately identify and segment the nuclei in the pathological images,with good robustness and generalization,which is helpful to play an auxiliary diagnostic role in practical applications.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to e-valuate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β Expression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The ex-pression of IL-1,IL-6,and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflam-matory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato-ry response.