With the rapid development of artificial intelligence, computational pathology has been seamlessly integrated into the entire clinical workflow, which encompasses diagnosis, treatment, prognosis, and biomarker discovery. This integration has significantly enhanced clinical accuracy and efficiency while reducing the workload for clinicians. Traditionally, research in this field has depended on the collection and labeling of large datasets for specific tasks, followed by the development of task-specific computational pathology models. However, this approach is labor intensive and does not scale efficiently for open-set identification or rare diseases. Given the diversity of clinical tasks, training individual models from scratch to address the whole spectrum of clinical tasks in the pathology workflow is impractical, which highlights the urgent need to transition from task-specific models to foundation models (FMs). In recent years, pathological FMs have proliferated. These FMs can be classified into three categories, namely, pathology image FMs, pathology image-text FMs, and pathology image-gene FMs, each of which results in distinct functionalities and application scenarios. This review provides an overview of the latest research advancements in pathological FMs, with a particular emphasis on their applications in oncology. The key challenges and opportunities presented by pathological FMs in precision oncology are also explored.
Humans ; Precision Medicine/methods* ; Medical Oncology/methods* ; Artificial Intelligence ; Neoplasms/pathology* ; Computational Biology/methods*

BACKGROUND: Preliminary study found that polylactic acid composite material could accelerate the bone construction rate, and the underlying mechanism still needs to be studied further. OBJECTIVE: To investigate the effect of lactic acid at different concentrations on osteoclast differentiation of mononuclear cells in mice. METHODS: Mouse RAW264.7 cells were cultured in DMEM with 0 (control group), 5, 10 and 20 mmol/L lactic acid, respectively, under the induction of 50 µg/L RANKL for 5 days. The effect of lactic acid concentration on the cell proliferation rate was analyzed by cell counting kit-8 assay. Tartrate resistant acid phosphatase positive polykaryotic cells were stained and counted with tartrate resistant acid phosphatase staining kit. mRNA expression levels of acid phosphatase 5, nuclear factor of activated T-cells 1 and RANK were detected by RT-PCR. Protein expression levels of cathepsin K and nuclear factor of activated T-cells 1 were detected by western blot assay. RESULTS AND CONCLUSION: (1) 5 mmol/L lactic acid produced the highest proliferation rate of raw264.7 cells, whereas the 20 mmol/L lactic acid produced lowest cell proliferation rate. Compared with the control group, the proliferation rate of raw264.7 cells by 10 mmol/L lactic acid was insignificant. (2) Tartrate resistant acid phosphatase staining showed the highest positive rate and mRNA expression levels of acid phosphatase 5, nuclear factor of activated T-cells 1 and RANK under the condition of 10 mmol/L lactic acid. (3) With the increase of lactic acid concentration, the expression level of cathepsin K increased, while the expression level of nuclear factor of activated T-cells 1 was on a decline. (4) Under the current experimental conditions, with the increase of lactic acid concentration, the ability of lactic acid to promote the osteoclast differentiation of mouse RAW264.7 cells is firstly increased and then decreased, and 10 mmol/L lactic acid was the optimal concentration to promote the osteoclast differentiation of mouse RAW264.7 cells. Lactic acid can affect the osteoclastic differentiation of mouse raw264.7 cells by nuclear factor of activated T-cells 1 in nuclear factor-KB signaling pathway.

Autopsy ; Betacoronavirus ; COVID-19 ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; SARS-CoV-2

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cell Culture Techniques ; methods ; Child ; Female ; Humans ; Induced Pluripotent Stem Cells ; cytology ; metabolism ; Male ; Middle Aged

This study aims to investigate the effects of fibroblast growth factor 21 (FGF-21) on learning and memory abilities and antioxidant capacity of D-galactose-induced aging mice. Kunming mice (37.1 +/- 0.62) g were randomly divided into normal control group, model group and FGF-21 high, medium and low dose groups (n = 8). Each group was injected in cervical part subcutaneously with D-galactose 180 mg x kg(-1) x d(-1) once a day for 8 weeks. At the same time, FGF-21-treated mice were administered with FGF-21 by giving subcutaneous injection in cervical part at the daily doses of 5, 2 and 1 mg x kg(-1) x d(-1). The normal control group was given with normal saline by subcutaneous injection in cervical part. At seventh week of the experiment, the learning and memory abilities of mice were determined by water maze and jumping stand tests. At the end of the experiment, the mice were sacrificed and the cells damage of hippocampus was observed by HE staining in each group. Reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and total antioxidant capacity (T-AOC) in the brain of mice were determined. The results showed that different doses of FGF-21 could reduce the time reaching the end (P < 0.01 or P < 0.05) and the number of touching blind side (P < 0.01 or P < 0.05) in the water maze comparing with the model group. It could also prolong the latency time (P < 0.05) and decrease the number of errors (P < 0.01 or P < 0.05) in the step down test. The result of HE staining showed that FGF-21 could significantly reduce brain cell damage in the hippocampus. The ROS and MDA levels of three different doses FGF-21 treatment group reduced significantly than that of the model group [(5.58 +/- 1.07), (7.78 +/- 1.92), (9.03 +/- 1.77) vs (12.75 +/- 2.02) pmol (DCF) x min(-1) x mg(-1), P < 0.01 or P < 0.05], [(2.92 +/- 0.71), (4.21 +/- 0.81), (4.41 +/- 0.97) vs (5.62 +/- 0.63) nmol x mg(-1) (protein), P < 0.01]. Comparing with the model group, the activities of SOD, GPx, CAT and T-AOC of the three different doses FGF-21 treatment groups were also improved in a dose-dependent manner. This study demonstrates that FGF-21 can ameliorate learning and memory abilities of D-galactose induced aging mice, improve the antioxidant abilities in brain tissue and delay brain aging. This finding provides a theoretical support for clinical application of FGF-21 as a novel therapeutics for preventing aging.
Aging ; drug effects ; Animals ; Antioxidants ; metabolism ; Brain ; drug effects ; Catalase ; metabolism ; Fibroblast Growth Factors ; pharmacology ; Galactose ; Glutathione Peroxidase ; metabolism ; Hippocampus ; drug effects ; Malondialdehyde ; metabolism ; Maze Learning ; drug effects ; Memory ; drug effects ; Mice ; Superoxide Dismutase ; metabolism

Animals ; Cellular Reprogramming ; Dentate Gyrus ; cytology ; Fibroblasts ; cytology ; Mice ; Neural Stem Cells ; cytology ; transplantation ; Swine

OBJECTIVETo investigate the therapeutic mechanism of point 8L54-through-point ST2S acupuncture with elongate needles in treating urinary retention after spinal cord injury.

METHODSThirty-five healthy Japanese rabbits (weight 2.5 +/- 0.25 kg, 3 months old, male or female), used as experimental subjects, were divided into 4 groups involving blank group, model group, acupuncture group, elongate needles group (5 rabbits in blank group, 10 rabbits in each of the other group 10). Modified Allen's method was used to cause spinal cord injury model for the model group, the acupuncture group and the elongate needles group, the blank group was only sham surgery. Immediately after spinal cord injury model,the elongated needle group was given the bilateral acupoints of the elongated needle penetration needling and electric stimulation, electrical stimulation 15 mm stimulation frequency of 20 to 40 times/mm, intensity 1.5 to 3 V the acupuncture group immediately was given ordinary electric needle acupuncture, given other disposals as the elongated needle group; model group was not given electric needle acupuncture, waiting 15 minutes, started to detect and record the observed indicator as the elongated needle group; the blank group was only sham surgery. The following indicators including the Tarlov score ,urinary bladder pressure point, the threshold urination, voided volume, were observed in the first day and the fifth day after surgery.

RESULTSThree groups of animals which modeled were urinary retention after operation. Compared to 1 d, Tarlov score of model group, acupuncture group and elongate needles group significantly improved at postoperative 5 d (P < 0.05). Compared with acupuncture group, the Tarlov score of elongate needles group had no significant difference at postoperative 5 d (P > 0.05). Compared with model group, values of urinary bladder pressure point decreased with varying degrees in the acupuncture group and elongate needles group at postoperative 5 d (P < 0.05); relative to the acupuncture group, the point of the bladder voiding pressure in the elongate needles group decreased more significantly at postoperative 5 d (P < 0.05); compared with model group, micturition threshold of acupuncture group and elongate needles group had been significantly improved at the fifth day after surgery (P < 0.05); relative to the acupuncture group, the improvement is more obvious in the elongate needles group. Compared with model group, voided volume of acupuncture group and elongate needles group had increased significantly at the fifth day after surgery (P < 0.05); relative to the acupuncture group, the increment is more evident in the elongate needles group (P < 0.05).

CONCLUSIONTo treat urinary retention after spinal cord injury, the method, which was point-through-point acupuncture with elongate needles in the "Zhibian" and "Shuidao", was better than general acupuncture method. The therapeutic mechanism may be related to stimulate peripheral nerve of bladder, and to rectify the dysfunction between detrusor and sphincter.

Acupuncture Points ; Acupuncture Therapy ; Animals ; Electroacupuncture ; Female ; Male ; Rabbits ; Spinal Cord Injuries ; complications ; Urinary Retention ; etiology ; therapy

OBJECTIVETo analyze the clinical characteristics of acute kidney injury (AKI) in critically ill childhood patients with influenza A virus (H1N1) and enterovirus 71 (EV71), and to study the significance of the serum creatinine and urine output in diagnosis of AKI.

METHODThe clinical data of AKI in critically ill children admitted to intensive care units (ICUs) with confirmed influenza A (H1N1) or enterovirus 71 infection (EV71 group) from Oct. 2009 to Oct. 2010.

RESULTTwenty-eight critically ill children were involved in the study. In H1N1 group, there were 18 cases including 6 males and 12 females, and the average age was 5.4 years. In EV71 group, there were 10 cases including 8 males and 2 females, and the average age was 1.1 years. In H1N1 group: 4 cases developed AKI, whose average number of involved organ was 5.3. Two children were classified as first stage completely recovered after treatment; three children who were classified as third stage died. In 14 children without AKI, the average number of involved organ was 3.0, four of these children died. In EV71 group: 3 cases (first stage) developed AKI and 3 cases' serum creatinine increased to 45.0 to 47.6 percent from baseline. The average number of involved organ was 5.7. All the six children died. The other 4 cases whose serum creatinine was normal, and the average number of involved organ was 3.0, recovered.

CONCLUSIONIn critically ill virus-infected children, more organs were involved in the patients who developed AKI. As to influenza A (H1N1) infected critically ill children, the prognosis was comparatively better if the children were classified as AKI stage 1 and received early effective treatment. On the contrary, the prognosis was comparatively worse for those with AKI stage 3. As to EV71 infected critically ill children, the prognosis was worse once AKI developed. As to diagnosis of AKI, the sensitivity of serum creatinine criteria seemed to be superior to the urine output criteria. However, the significance of the serum creatinine and urine output in diagnosis of AKI still needs to be investigated in the future in large scale clinical studies.

Acute Kidney Injury ; diagnosis ; etiology ; virology ; Child ; Child, Preschool ; Critical Illness ; Enterovirus ; pathogenicity ; Enterovirus Infections ; complications ; virology ; Female ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype ; pathogenicity ; Influenza, Human ; complications ; virology ; Intensive Care Units ; Male ; Prognosis ; Retrospective Studies

Objective To investigate the effect of implantation of bone marrow mononuclear cells (BM-MNCs)on neovascularization and ischemic-type intrahepatic biliary lesion in rabbits.Methods The animals were divided into the sham-operation group, experimental model group and BM-MNCs implantation group with 10 rabbits in each. The animal model of ischemic-type intrahepatic biliary lesion was established by clamping the hepatic artery and common bile duct. The BM-MNCswere isolated from the tibial plateau by means of density gradient centrifugation and were implanted through the common hepatic artery. Changes of some biochemical markers such as ALT, AST, ALP,γ-GT, TBIL and DBIL etc. were detected. In 4 weeks after operation, the cholangiography, histopathological manifestation, differentiation of BM-MNCs, and microvessel density were observed.Results At each observation time, the degree of change of biochemical markers in group C was lower than that in group B. The engrafted cells could differentiate into vascular endothelial cells. The intrahepatic biliary lesion of group B was severer than that of group C but had fewer new capillary blood vessels around it. Conclusion The implantation of BM-MNCs can promote neovascularization and increase blood supply to the ischemic bile duct to diminish or prevent ischemic-type intrahepatic biliary lesion.

OBJECTIVETo investigate the effect of controlled hypotension using different drugs on gastrointestinal perfusion and bleeding volume in nasal endoscopic surgery.

METHODSThirty ASA class I or II patients scheduled for nasal endoscopic surgery were randomized into three groups, including a routine general anesthesia group (group A) and two controlled hypotension groups (groups B and C). After anesthesia induction, anesthesia was maintained with 1%-2% isoflurane and vecuronium. ECG, mean arterial blood pressure (MAP), heart rate (HR), SpO(2) and PETCO(2) were continuously monitored. TRIP tonometry catheter 14 F was inserted into the stomach and connected to Tonocap (Datex-Ohmeda, Finland ). In groups B and C, hypotension was induced with isoflurane (1%-2%) and sodium nitroprusside (0.3-3 microg.kg(-1).min(-1)), and with isoflurane (1%-2%) and glonoine (0.5-5 microg.kg(-1).min(-1)), respectively, and the MAP was reduced to 50-55 mmHg in 10-15 min. In groups B and C, blood samples were taken for blood gas analysis after anesthesia (T(0)), after acute hypervolemic hemodilution (T(1)), at 30 and 60 min after controlled hypotension (T(2) and T(3)), and 30 min after recovery from hypotension (T(4)). In group A, blood samples were taken at different time points in the perioperative period.

RESULTSThe patients in groups B and C had smaller bleeding volume than those in group A. HR was decreased after moderate acute hypervolemic hemodilution, and increased after controlled hypotension (T(2) and T(3)) in comparison with that at T(1) to a level similar to that at T(0). No significant changes were found in pHi at T(2) and T(3) in comparison with that at T(1) in the three groups.

CONCLUSIONWhen appropriate measures are taken, induced hypotension at 50-55 mmHg does not necessarily produce disturbance in gastrointestinal perfusion. Induced hypotension with glonoin can decrease the bleeding volume better than sodium nitroprusside in nasal endoscopic surgery.

Adolescent ; Adult ; Blood Loss, Surgical ; prevention & control ; Endoscopy ; Female ; Hemodilution ; methods ; Humans ; Hypotension, Controlled ; methods ; Intestines ; blood supply ; Male ; Middle Aged ; Nitroglycerin ; therapeutic use ; Nitroprusside ; therapeutic use ; Paranasal Sinuses ; surgery ; Young Adult