ObjectiveZheng’s San Qi San (ZSQS) power, a classic traditional Chinese medicine (TCM) formula, is used for treating soft tissue injuries involving muscles, tendons, and ligaments. However, its underlying therapeutic mechanisms remain unclear. This study aimed to screen and identify pharmaceutically active ingredients and their candidate biomolecule targets, and further elucidate the molecular mechanism of ZSQS in the treatment of skeletal muscle injury. MethodsNetwork pharmacology was employed to construct “ZSQS-component-target”, “protein-protein interaction (PPI)” and “active ingredient-core protein-pathway” networks to predict the key active ingredients and potential core targets of ZSQS for skeletal muscle injury. The predicted results were then validated via microarray data from the GEO database. Molecular docking was then performed to assess the binding ability between the screened active ingredients of ZSQS and the candidate core targets. Moreover, liquid chromatography-mass spectrometry (LC-MS) was used for qualitative and quantitative analysis to verify the active components of the drug and ZSQS serum. Finally, an animal model of eccentric exercise-induced skeletal muscle injury and a myotube cell model of oxidative stress-induced injury were established to validate the effects of ZSQS and its interventional effects on the biological functions of critical targets, thereby demonstrating the potential therapeutic mechanism of ZSQS. ResultsAmong the 111 active components identified in ZSQS and their corresponding 204 targets related to the skeletal muscle injury repair process, 14 core targets (including AKT1) and 4 core active components (quercetin, luteolin, kaempferol, and β‑sitosterol) were screened out, while the corresponding metabolites of quercetin, luteolin and kaempferol were detected in the ZSQS serum. Among these targets, 5 candidate genes (IL-6, CASP3, HIF1A, STAT3, and JUN) overlapped with the differential expression screening results with GEO data, and IL-6 was confirmed to be enriched in the PI3K/AKT pathway. Combined with the prediction results of the AKT expression levels, these findings suggest that the phosphorylation level of AKT1 plays a core role in the therapeutic mechanism of ZSQS. Molecular docking analysis further revealed that the PH domain of AKT1 had high binding energy with all 4 core active components, as verified by LC-MS. Finally, animal model studies have shown the promoting effect of ZSQS administration on skeletal muscle injury repair and its possible antioxidant damage mechanism. Cell model studies further demonstrated that ZSQS-containing serum, core active ingredient combination therapy, and quercetin monomer could increase the phosphorylation level of AKT, promote the nuclear translocation of Nrf2, upregulate the expression of downstream antioxidant enzymes (SOD, GPx, and GR), and inhibit the expression of inflammatory factors (IL-6 and TNF-α), thereby alleviating oxidative stress and the inflammatory response. ConclusionZSQS alleviates skeletal muscle injury mainly by activating the AKT/Nrf2 signaling pathway, enhancing cellular antioxidant and anti-inflammatory capabilities. The results of this study provide a scientific basis for the clinical application and modernized development of ZSQS.

ObjectiveTo investigate the effects of Trpc6 knockout on chronic lipopolysaccharide （LPS）-induced myocardial inflammation and fibrosis in mice and its potential mechanisms. MethodsMale C57BL/6 wild-type （WT） mice and Trpc6 knockout （Trpc6^-/-） mice of the same background were randomly divided into four groups： WT control， WT+LPS （200 μg/kg）， Trpc6^-/- control， and Trpc6^-/-+LPS （200 μg/kg）. Group with LPS received intraperitoneal LPS injections for 21 consecutive days to induce chronic myocardial inflammatory injury. Cardiac ultrasound assessed changes in left ventricular ejection fraction （EF）， left ventricular shortening fraction （FS）， and cardiac output （CO）. Hematoxylin and eosin （HE） staining and periodic acid-Schiff （PAS） staining were used to examine morphological alterations in myocardial tissue. Masson’s trichrome staining was used to assess myocardial fiber alterations； Western blot analysis was used to measure myocardial tissue expression of transient receptor potential calcium channel 6 （TRPC6）， NOD-like receptor family pyrin domain-containing 3 inflammasome （NLRP3），absent in melanoma 2 inflammasome （AIM2）， Caspase-1， interleukin （IL）-6， and IL-1β in mouse myocardial tissue. ResultsCompared with the WT control group， the WT+LPS group exhibited decreased cardiac EF （P<0.01）， FS （P<0.01）， and CO （P<0.05）， along with significantly increased myocardial tissue damage， glycoprotein deposition， and fibrosis （P<0.01）. Further analysis revealed that compared with the WT control group， the WT+LPS group exhibited markedly increased myocardial tissue expression of TRPC6， NLRP3， AIM2， Caspase-1， IL-6， and IL-1β （P<0.01）. Compared with the WT+LPS group， mice in the Trpc6^-/- +LPS group exhibited elevated EF （P<0.01） and FS （P<0.05）， along with reduced myocardial tissue injury， glycoprotein deposition， and fibrosis （P<0.05）. ConclusionChronic LPS treatment can activate NLRP3/AIM2 inflammasomes through the up-regulation of TRPC6 expression， and then lead to chronic myocardial inflammatory injury and fibrosis， while Trpc6 knockdown can reduce myocardial inflammatory injury and fibrosis， and the mechanism is related to inhibiting the activation of NLRP3/AIM2 inflammasomes.

Gastric cancer is a high-incidence malignancy that poses a serious threat to public health in China, ranking among the top three cancers in both incidence and mortality. The majority of patients are diagnosed at an advanced stage, resulting in limited treatment options and poor prognosis. To address key challenges in gastric cancer diagnosis and treatment, a research team led by Professor Jiafu Ji at Peking University Cancer Hospital has focused on the project "Development and Dissemination of Precision Medicine Approaches in Gastric Cancer Management". Through a series of high-quality multicenter clinical studies, the team established a set of new international standards in perioperative treatment, individua-lized drug selection, intelligent noninvasive diagnostics, and novel immunotherapy strategies. These advances have significantly improved treatment efficacy and reduced surgical trauma, achieving key technological breakthroughs in diagnosis, therapy, and mechanistic understanding, and systematically enhancing outcomes for gastric cancer patients. The project ' s findings had a broad international impact, including hosting China ' s first International Gastric Cancer Congress. Through nationwide dissemination, they have promoted the development of precision diagnosis and treatment of gastric cancer as a discipline, and led the formulation of the National Health Commission's guidelines for gastric cancer diagnosis and treatment. In recognition of its achievements, the project was awarded the First Prize of the 2024 Chinese Medical Science and Technology Award.
Stomach Neoplasms/genetics* ; Humans ; Precision Medicine/methods* ; China ; Immunotherapy/methods*

OBJECTIVES: To investigate the effects of quercetin on cuproptosis and L-type calcium currents in the myocardium of diabetic rats. METHODS: Forty SD rats were randomized into control group and diabetic model groups. The rat models of diabetes mellitus (DM) induced by high-fat and high-sugar diet combined with streptozotocin (STZ) injection were further divided into DM model group, quercetin treatment group, and empagliflozin treatment group (n=10). Blood glucose and body weight were measured every other week, and cardiac function of the rats was evaluated using echocardiography. HE staining, Sirius red staining, and wheat germ agglutinin (WGA) analysis were used to observe the changes in myocardial histomorphology, and serum copper levels and myocardial FDX1 expression were detected. In cultured rat cardiomyocyte H9c2 cells with high-glucose exposure, the effects of quercetin and elesclomol, alone or in combination, on intracellular CK-MB and LDH levels and FDX1 expression were assessed, and the changes in L-type calcium currents were analyzed using patch-clamp technique. RESULTS: The diabetic rats exhibited elevated blood glucose, reduced body weight, impaired left ventricular function, increased serum copper levels and myocardial FDX1 expression, decreased L-type calcium currents, and prolonged action potential duration. Quercetin and empagliflozin treatment significantly lowered blood glucose, improved body weight, and restored cardiac function of the diabetic rats, and compared with empagliflozin, quercetin more effectively reduced serum copper levels, downregulated FDX1 expression, and enhanced myocardial L-type calcium currents in diabetic rats. In H9c2 cells, high glucose exposure significantly increased myocardial expressions of FDX1, CK-MB and LDH, which were effectively lowered by quercetin treatment; Elesclomol further elevated FDX1, CK-MB and LDH levels in the exposed cells, and these changes were not significantly affected by the application of quercetin. CONCLUSIONS Quercetin ameliorates myocardial injury in diabetic rats possibly by suppressing myocardial cuproptosis signaling and restoring L-type calcium channel activity.
Animals ; Quercetin/pharmacology* ; Calcium Channels, L-Type/metabolism* ; Diabetes Mellitus, Experimental/metabolism* ; Rats, Sprague-Dawley ; Rats ; Myocytes, Cardiac/drug effects* ; Myocardium/pathology* ; Male

OBJECTIVE: To investigate the mechanism of autophagy in regulating bacterial translocation in intestinal infection caused by hypervirulent Klebsiella pneumonia (hvKp) and explore the method of reducing translocation infection of intestinal bacteria. METHODS: Fifty C57BL/6J mice were divided into gavage group (n = 40) and control group (CO group, n = 10). The gavage group was orally administered with 200 μL/d of hvKp (colony count of 10⁹ CFU/mL) continuously for 5 days to establish a hvKp intestinal infection model. CO group was given an equal amount of normal saline. After the experiment, the mice were anesthetized with lsofluraneand euthanized with cervical dislocation under anesthesia. Peripheral venous blood of mice was collected to detect bacterial translocation by 16S rDNA sequencing, then divided into translocation group (BT+ group) and non-translocation group (BT- group). Hematoxylin-eosin (HE) staining was used to evaluate intestinal morphology. The ultrastructural changes of intestinal tissues were observed by electron microscope. The levels of intestinal oxidative stress indicators such as superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione peroxidase (GPx) were measured. Translocation was detected by in situ hybridization. The expression of tight junction protein microtubule-associated protein 1 light chain 3-II (LC3-II) and autophagy protein Beclin-1 were measured by Western blotting. The mRNA expression of tight junction proteins ZO-1 and Claudin-2 were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of autophagy protein and tight junction protein were observed by immunofluorescence. RESULTS: Two out of 40 mice in the gavage group died after developing aspiration pneumonia. All mice in the CO group survived. The 16S rDNA sequencing results showed that no bacteria were detected in the peripheral blood of the CO group, but bacteria were detected in the peripheral blood of 18 mice in the gavage group, with a bacterial translocation rate of 47.4%. The BT- and BT+ groups showed intestinal mucosal tissue damage, with severe damage in the BT+ group. Compared with the CO group, the level of MDA in the BT- and BT+ groups were significantly increased, while the activities of SOD and GPx were significantly decreased. Compared with the BT- group, the MDA level in the BT+ group further increased, while the SOD and GPx activities further decreased [MDA (mmol/mg): 2.98±0.11 vs. 2.48±0.11, SOD (U/mg): 62.40±5.45 vs. 73.40±4.08, GPx (U/mg): 254.72±10.80 vs. 303.55±8.57, all P < 0.01]. The results of in situ hybridization detection showed that after continuous gastric lavage for 5 days, displaced hvKp was detected in the intestinal mucosal lamina propria and liver tissue of the BT+ group. Compared with the CO group, the protein expressions of LC3-II and Beclin-1 in the BT- and BT+ groups were significantly increased. The protein expressions of LC3-II and Beclin-1 in the BT+ group were obviously lower than those in the BT- group (LC3-II/β-actin: 0.38±0.04 vs. 0.70±0.09, Beclin-1/β-actin: 0.62±0.05 vs. 0.86±0.05, both P < 0.01), and there were autophagosomes in the intestinal mucosa. These results indicated that intestinal mucosal autophagy was activated after hvKp continuous gavage. Compared with CO group, the mRNA expressions of ZO-1 and Claudin-2 in the BT- and BT+ groups were significantly decreased. Compared with the BT- group, the mRNA expressions of ZO-1 and Claudin-2 in the BT+ group was further reduced [ZO-1 mRNA (2^-ΔΔCT): 0.78±0.06 vs. 0.88±0.06, Claudin-2 mRNA (2^-ΔΔCT): 0.40±0.04 vs. 0.70±0.06, both P < 0.01]. The immunofluorescence results showed that the fluorescence intensity of LC3-II, Beclin-1, ZO-1, and Claudin-2 in the BT+ group was significantly lower than that in the BT- group. CONCLUSION HvKp can activate intestinal mucosal autophagy and reduce the damage to intestinal mucosal barrier function by down-regulating oxidative stress level, reduce the occurrence of bacterial translocation.
Animals ; Oxidative Stress ; Mice, Inbred C57BL ; Autophagy ; Intestinal Mucosa/microbiology* ; Bacterial Translocation ; Mice ; Klebsiella Infections/microbiology* ; Superoxide Dismutase/metabolism* ; Beclin-1

OBJECTIVE: To evaluate the effectiveness of minimally invasive reduction and ulna bicortical angulation intramedullary fixation in the management of Bado typeⅠMonteggia fracture in pediatric patients. METHODS: Between August 2018 and August 2020, the clinical data of 15 pediatric patients diagnosed with Bado typeⅠfresh Monteggia fracture were retrospectively analyzed. There were 11 males and 4 females. The left side was implicated in 5 cases, while the right side was involved in 10 cases. The age ranged from 4 to 12 years old. There were a total of 10 cases of upper ulna fractures and 5 cases of middle ulna fractures. Among these, the ulnar fracture line presented as transverse or short oblique in 9 cases, and long oblique or spiral in 6 cases. The pediatric patients underwent treatment utilizing minimally invasive reduction and ulna bicortical angulation intramedullary fixation. The effectiveness of the treatment was assessed based on the Mayo elbow scoring system. RESULTS: The follow-up period for all 15 cases ranged from 6 to 24 months. Among them, the occurrence of needle tail irritation was observed in 3 cases, all of which exhibited satisfactory healing following routine disinfection and dressing change. The other children had no re dislocation of the radial capitulum, no epiphyseal injury, no osteofascial compartment syndrome, elbow instability and other complications. The degree of limitation of daily life, range of motion of joints, pain level and appearance of limbs were recorded at the last follow-up. According to Mayo elbow scoring system, 12 cases were excellent and 3 cases were good. CONCLUSION The minimally invasive reduction and ulna bicortical angulation intramedullary fixation technique is a simple and effective treatment for Bado typeⅠfresh Monteggia fractures in children.
Humans ; Male ; Female ; Child ; Monteggia's Fracture/surgery* ; Child, Preschool ; Minimally Invasive Surgical Procedures/methods* ; Fracture Fixation, Intramedullary/methods* ; Retrospective Studies

OBJECTIVE: To investigate the efficacy and safety of oblique lateral interbody fusion(OLIF) channel technique combined with pedicle screw internal fixation in the treatment of single-segment lumbar intervertebral space/vertebral body infection. METHODS: A retrospective analysis was conducted on 23 patients who underwent surgical treatment for lumbar infection from January 2021 to December 2022. The patients were divided into the OLIF channel group and the traditional open surgery group according to the surgical methods. There were 16 cases in the OLIF channel group, including 9 males and 7 females, with an average age of (68.5±12.1) years old;there were 7 cases in the traditional open surgery group, including 4 males and 3 females, with an average age of (75.0±3.2) years old. The operation time, intraoperative blood loss, hospital stay, incision length, visual analogue scale(VAS), activities of daily living (ADL) score, Oswestry disability index (ODI), erythrocyte sedimentation rate(ESR), C-reactive protein(CRP) before and 1 week and 3 months after the operation, and the intervertebral fusion status on the last follow-up CT were compared between the two groups. RESULTS: Compared with the open surgery group, the OLIF channel group had shorter operation time (209.87±31.5) min vs. (246.0±42.7) min, less intraoperative blood loss (225.625±91.1) ml vs. (364.2±74.8) ml, and shorter incision length (6.1±1.2) vs. (14.0±1.4) cm, and the differences were statistically significant(P<0.05). Before and 1 week and 3 months after the operation, the lumbar VAS in the OLIF group were (6.3±0.6), (2.8±0.7), (1.1±0.5), and those in the traditional open surgery group were (6.4±0.6), (3.4±0.5), (1.2±0.3);the ADL scores in the OLIF group were (45.0±4.5), (60.3±4.3), (94.1±4.2), and those in the open group were (46.4±5.6), (60.7±4.5), (92.9±4.9); the ODI scores in the OLIF group were (86.3±2.9)%, (69.5±4.1)%, (23.0±3.2)%, and those in the open group were (87.3±3.8)%, (69.8±4.2)%, (23.8±3.6)%, all of which showed significant improvement(P<0.05). Three months after the operation, CRP, PCT, and ESR were significantly lower than those before the operation, and CRP and PCT returned to normal, while ESR was still slightly elevated in some patients. The last follow-up CT showed that continuous trabecular bone formation was observed between the upper and lower endplates of the surgical segments in all patients, and the fusion time was (8.7±4.5) months. CONCLUSION The OLIF channel technique combined with posterior internal fixation is a minimally invasive and effective treatment method, which can effectively control infection, relieve pain, and improve the quality of life of patients. Compared with traditional open surgery, it has the advantages of minimally invasive, shorter operation time, and less intraoperative blood loss.
Humans ; Male ; Female ; Spinal Fusion/methods* ; Lumbar Vertebrae/microbiology* ; Aged ; Middle Aged ; Retrospective Studies ; Aged, 80 and over ; Pedicle Screws ; Infections/surgery*

OBJECTIVE: To investigate the clinical efficacy and safety of ultrasound-guided closed reduction and internal fixation using Kirschner wire for the treatment of olecranon fractures of the ulna in children. METHODS: Between January 2019 and January 2021, 13 children with olecranon fracture were treated with ultrasound-guided closed reduction and percutaneous Kirschner wire internal fixation, including 10 males and 3 females. The age ranged from 3 to 14 years old. Children with ulnar olecranon fractures were evaluated using the Gicquel scoring system. The clinical evaluation encompassed postoperative pain, functional status, and range of motion, with a maximum score of 15 points. The radiological assessment contributed an additional 4 points. A cumulative score of more than 18 scores was classified as excellent, more than 17 scores as good, more than16 scores as fair, and less than 16 scores as poor. Clinical assessment:A score of 14 indicates excellent performance, a score of 13 reflects good performance, a score of 12 denotes fair performance, and a score of less than 11 signifies poor performance. RESULTS: A total of 13 patients were followed up, with a duration ranging from 6 to 12 months. According to the Gicquel scoring criteria, the comprehensive evaluation of clinical and radiographic findings yielded 10 excellent and 3 good outcomes. Evaluation based solely on clinical findings resulted in 13 excellent outcomes. CONCLUSION Ultrasound-guided percutaneous cross Kirschner wire fixation for children's olecranon fracture has the advantages of less trauma, rapid recovery, less fluoroscopy, and good recovery of elbow function. The clinical effect is satisfactory.
Humans ; Child ; Male ; Female ; Fracture Fixation, Internal/instrumentation* ; Ulna Fractures/physiopathology* ; Bone Wires ; Child, Preschool ; Adolescent ; Olecranon Process/surgery* ; Ultrasonography ; Closed Fracture Reduction/methods* ; Olecranon Fracture