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.

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, functional impairment, and neuropsychiatric symptoms. It represents the most prevalent form of dementia among the elderly population. Accumulating evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of AD. Notably, elevated levels of oxidative stress have been observed in the brains of AD patients, where excessive reactive oxygen species (ROS) can cause extensive damage to lipids, proteins, and DNA, ultimately compromising neuronal structure and function. Amyloid β‑protein (Aβ) has been shown to induce mitochondrial dysfunction and calcium overload, thereby promoting the generation of ROS. This, in turn, exacerbates Aβ aggregation and enhances tau phosphorylation, leading to the formation of two pathological features of AD: extracellular Aβ plaque deposition and intracellular neurofibrillary tangles (NFTs). These events ultimately culminate in neuronal death, forming a vicious cycle. The interplay between oxidative stress and these pathological processes constitutes a core link in the pathogenesis of AD. The signaling pathways mediating oxidative stress in AD include Nrf2, RCAN1, PP2A, CREB, Notch1, NF‑κB, ApoE, and ferroptosis. Nrf2 signaling pathway serves as a key regulator of cellular redox homeostasis, exerts important antioxidant capacity and protective effects in AD. RCAN1 signaling pathway, as a calcineurin inhibitor, and modulates AD progression through multiple mechanisms. PP2A signaling pathway is involved in regulating tau phosphorylation and neuroinflammation processes. CREB signaling pathway contributes to neuroplasticity and memory formation; activation of CREB improves cognitive function and reduce oxidative stress. Notch1 signaling pathway regulates neuronal development and memory, participates in modulation of Aβ production, and interacts with Nrf2 toco-regulate antioxidant activity. NF‑κB signaling pathway governs immune and inflammatory responses; sustained activation of this pathway forms “inflammatory memory”, thereby exacerbating AD pathology. ApoE signaling pathway is associated with lipid metabolism; among its isoforms, ApoE-ε4 significantly increases the risk of AD, leading to elevated oxidative stress, abnormal lipid metabolism, and neuroinflammation. The ferroptosis signaling pathway is driven by iron-dependent lipid peroxidation, and the subsequent release of lipid peroxidation products and ROS exacerbate oxidative stress and neuronal damage. These interconnected pathways form a complex regulatory network that regulates the progression of AD through oxidative stress and related pathological cascades. In terms of therapeutic strategies targeting oxidative stress, among the drugs currently used in clinical practice for AD treatment, memantine and donepezil demonstrate significant therapeutic efficacy and can improve the level of oxidative stress in AD patients. Some compounds with antioxidant effects (such asα-lipoic acid and melatonin) have shown certain potential in AD treatment research and can be used as dietary supplements to ameliorate AD symptoms. In addition, non-drug interventions such as calorie restriction and exercise have been proven to exerted neuroprotective effects and have a positive effect on the treatment of AD. By comprehensively utilizing the therapeutic characteristics of different signaling pathways, it is expected that more comprehensive multi-target combination therapy regimens and combined nanomolecular delivery systems will be developed in the future to bypass the blood-brain barrier, providing more effective therapeutic strategies for AD.

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.

AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.

This study investigated the effect of different carrier materials on the in vitro properties of progesterone solid dispersions. The solid dispersions of the insoluble drug progesterone were prepared by hot melt extrusion technique using rheological properties as the index of investigation, and the in vitro properties of the solid dispersions were characterized. Scanning electron microscope revealed solid dispersions with rough surfaces and agglomerated microstructures into irregular lumpy particles. Differential scanning calorimetry and powder X-ray diffraction showed the change of progesterone crystalline form in solid dispersions from crystalline to amorphous state. In vitro dissolution studies showed that solid dispersions prepared with different carrier materials can effectively improve the dissolution rate of drugs. The results of the study showed that the type of carrier material had a significant effect on the in vitro properties of solid dispersions, providing a reference for the study of solid dispersions in the controlled release of insoluble drugs.

Needle-free injection technology (NFIT) refers to the drug delivery systems in which drugs are propelled as high-speed jet streams using any of the pressure source to penetrate the skin to the required depth. NFIT is a promising drug delivery system as it enables the injection of liquids, powders, and depot/projectiles, and has the advantages of preventing needle stick accidents, improving drug bioavailability, eliminating needle-phobia, increasing vaccine immunity, simplifying operations and is convenient for patients to use. NFIT and its research background, the structure and classification of needle-free jet injectors (NFJI), drugs that can be delivered using NFJI and the factors affecting the injection effect are comprehensively reviewed in this paper. The limitations and potential development directions are summarized to provide a theoretical basis for the application and development of NFIT.

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 explore the clinical characteristics and treatment scheme of periprosthetic joint infection(PJI)caused by Cutibacterium avidum(C.avidum).Methods The diagnosis and treatment process of a patient with PJI caused by C.avidum was summarized,and relevant literatures in the database were retrieved for review.Results A 65-year-old female patient with body mass index(BMI)of 31.1 kg/m2 underwent left humeral head prosthesis replacement surgery following a left proximal humerus fracture.Ten months after the surgery,the pa-tient exhibited poor wound healing and oozing,along with limited movement of the left shoulder joint,and was diag-nosed infection following shoulder arthroplasty.Patient underwent debridement of the infected lesion and removal of the prosthesis.The tissue,bone cement and prosthesis were cultured for C.avidum.Four literatures were re-trieved and screened,a total of 30 patients with PJI(28 cases hip joint infection and 2 cases shoulder joint infection)caused by C.avidum were reported through literature retrieval,and 78.6％(n=22)total hip arthroplasty(THA)surgeries were performed using direct anterior approach(DAA).The positive rate of preoperative joint fluid culture was 71.4％,29 cases underwent surgical combined with sensitive antimicrobials treatment.Except for one patient who had repeated infection and underwent three surgeries,other patients had a good prognosis.Conclusion PJI caused by C.avidum is mostly seen in THA patients who are obese and undergo DAA,with a few cases reported after shoulder arthroplasty.The high sensitivity of preoperative joint fluid culture provides an important basis for the development of surgical strategies and anti-infection protocols.

Orodispersible films (oral dispersible films), a novel form of oral solid dosage forms, are widely used for patients with dysphagia and those with uncontrollable autonomic behavior. In this study, suvorexant orodispersible film was prepared by hot melt extrusion technology, and the disintegration time, mechanical properties, in vitro dissolution and pharmacokinetics were evaluated, compared with other orodispersible films and commercially available tablets Belsomra. All experiments were approved by the Committee on the Management and Use of Laboratory Animals of Academy of Military Medical Sciences (IACUC-DWZX-2024-504). The results showed that the dissolution rate of suvorexant orodispersible film was faster and the mechanical strength was better than that of other commercially available orodispersible film, which could meet the needs of storage and transportation. Differential scanning calorimetry and X-ray diffraction results showed that suvorexant was dispersed within the orodispersible film in an amorphous state. The in vitro dissolution of the film was observed to be four times faster than that of the commercial tablets, achieving complete dissolution within five minutes. Pharmacokinetic evaluations in Beagle dogs revealed that the self-formulated orodispersible film exhibited no significant differences in the area under the blood concentration-time curve when compared with Belsomra. However, the film showed a faster onset of action, with a peak time that was twice as rapid, and a maximum blood concentration that was twice as high as that of Belsomra. Leveraging hot melt extrusion technology, the suvorexant orodispersible film offers a straightforward, continuous production process with consistent quality. It serves as an excellent platform for the development of solvent-free film preparations tailored for patients with special needs.