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.

Attention deficit hyperactivity disorder （ADHD） is often accompanied by tic disorder. The core pathogenesis is considered to be ministerial fire scorching yin and internal stirring of deficient wind， which leads to disharmony between the body and spirit， resulting in clinical manifestations. The treatment principles emphasize nourishing yin fluids， calming ministerial fire， and extinguishing endogenous wind （内风）. The method of nourishing yin fluids is applied throughout the entire treatment process， commonly using ingredients such as Shudihuang （Rehmanniae Radix Praeparata）， Shanzhuyu （Corni Fructus）， Gouqizi （Lycii Fructus）， Wuweizi （Schisandrae Chinensis Fructus）， and Tusizi （Cuscutae Semen）. These are combined with approaches to harmonize the zang-fu organs， primarily including extinguishing liver wind， clearing heart fire， nourishing kidney water， and strengthening spleen earth， thereby stabilizing ministerial fire and extinguishing endogenous wind. Additionally， emotional regulation and smoothing emotional constraint are essential to improve clinical symptoms in children with ADHD comorbid with tic disorder.

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

Objective:This study aimed to integrate RNA-seq data to identify key genes associated with macrophage-ferroptosis and develop a prognostic model for hepatocellular carcinoma(HCC).Methods:We retrieved a dataset from the GEO database containing transcriptome data and clinical information for 163 samples.Macrophage-related genes were identified using WGCNA and immune infiltration analyses.Ferroptosis-related genes from the FerrDbV2 database were intersected with differentially expressed genes to obtain significant macrophage-ferroptosis-related genes.Hub genes were screened via protein interaction network construction,and key genes were identified using four machine learning algorithms.These genes exhibited significant expression differences between cancer and normal tissues and were closely linked to patient prognosis.ROC curve and KM survival analyses were performed,and expression levels were validated at the transcriptome and proteome levels.Results:Four key genes RRM2,KIF20A,PCK2,and PDK4 were identified and evaluated.RRM2 and KIF20A demonstrated high importance in classification prediction models and reliable performance in ROC and KM analyses(AUC＞0.9,P＜0.05).These genes regulate cancer cell proliferation/survival and macrophage polarization/function,influencing the tumor microenvironment and HCC progression.Conclusion:RRM2 and KIF20A regulate cancer cell proliferation and survival,modulate macrophage polarization and function,and influence the immune response in the tumor microenvironment.They can serve as prognostic biomarkers and potential immunotherapy targets for hepatocellular carcinoma.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Objective:As medical demands rose rapidly and innovative pharmaceuticals continuously launched onto the market,the National Essential Medicines List(NEML)confronted a novel challenge whether or not to include new medicines.The practice of WHO including new medicines in the WHO Essential Medicines List(WHO EML)was analyzed to provide references for the adjustment of NEML.Methods:Based on the theory of the right to life and health,it explored the theoretical basis of WHO incorporating new medicines into WHO EML.The cancer medicines were taken as the examples to investigate evaluation criteria.Results:For the selection of new medicines,WHO refined multi-dimensional evaluation criteria and took targeted measures to improve selection process and management system.Conclusion:When China attempted to include new drugs in the NEML,it was necessary to adjust selection concept,optimize selection process,improve NEML structure and content,improve selection criteria and strengthen the construction of selection and management guarantee system.

OBJECTIVE: To assess the diagnostic value of whole exome sequencing (WES) for fetuses undergone induced abortion due to structural abnormalities. METHODS: A retrospective analysis was carried out on 43 aborted fetuses with negative results for copy number variation (CNV) testing from January 2023 to June 2024 at Northwest Women's and Children's Hospital. Trio-WES was carried out on the tissues from the aborted fetuses. This study has been approved by the Ethics Committee of the Hospital (Ethics No. 21-036). RESULTS: Among the 43 abortic fetuses, WES has detected pathogenic variants in 15 cases, with a total of 9 pathogenic variants, 5 suspected pathogenic variants, and 5 variants of uncertain significance. No definite pathogenic variants were detected in the remaining 28 cases. CONCLUSION For fetuses with structural abnormalities and negative results from CNV testing, WES can increase the diagnostic rate and facilitate etiological diagnosis and genetic counseling.
Humans ; Female ; Exome Sequencing/methods* ; Pregnancy ; DNA Copy Number Variations/genetics* ; Retrospective Studies ; Adult ; Prenatal Diagnosis/methods* ; Abortion, Induced ; Fetus/abnormalities* ; Congenital Abnormalities/diagnosis* ; Genetic Testing ; Aborted Fetus/abnormalities*

Objective:To investigate the long-term outcomes of using 3D-printed preformed titanium meshes in repair and reconstruction of orbital region.Methods:A retrospective analysis was conducted on patients with tumors invading the naso-orbito-maxillary region who underwent surgical resection and repair/reconstruction with 3D-printed preformed titanium meshes. The patients were collected at three medical centers (the Third Affiliated Hospital of Sun Yat-sen University, Xijing Hospital of Air Force Military Medical University, and Shenzhen Longgang District Ear, Nose and Throat Hospital) from 2016 to 2023. Tumor extent was evaluated radiologically, and the surgical approaches, reconstruction outcomes, surgical complications, and long-term follow-up results were analyzed.Results:A total of 46 patients from the three centers were included in this study, comprising 27 males and 19 females, with an average age of 51 years (range: from 13 to 86 years). Among them, 4 patients had benign tumors, while the remaining 42 had malignant tumors. The median follow-up duration was 60.7 months (range: from 19.0 to 75.0 months). Postoperatively, symmetrical globe position was achieved in 38 cases without significant diplopia; 4 cases exhibited enophthalmos without diplopia, and 4 cases had enophthalmos with diplopia. Twelve patients received preoperative radiotherapy, and 30 patients received postoperative radiotherapy. Six patients developed enophthalmos, and 6 experienced titanium mesh exposure after radiotherapy. Following treatment completion, 3 patients underwent repair using frontal flaps, 1 using a superficial temporal artery island flap, and 2 using free flaps. All remaining patients showed no postoperative infections, and their wounds healed normally.Conclusion:The application of 3D-printed preformed titanium mesh enables precise repair of postoperative defects in patients with naso-orbital tumors, facilitating reliable reconstruction of the orbital and facial contours with straightforward operation and dependable outcomes.

Objective:To analyze the efficacy and safety of modified associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in the treatment of patients with primary liver cancer.Methods:Clinical data of 83 patients with hepatocellular carcinoma (HCC) undergoing hemihepatectomy in the Department of Hepatobiliary and Pancreatic Tumor Surgery of Gansu Provincial Cancer Hospital between January 2022 and November 2023 were retrospectively analyzed, including 53 males and 30 females, aged (54.0±6.5) years. According to the treatment protocol, patients were divided into the control group ( n=41), in which patients underwent traditional ALPPS, and the observation group ( n=42), in which patients underwent modified ALPPS (occlusion of portal venous branch using vascular clips, combined with radiofrequency ablation for physical separation of the diseased lobe, without liver mobilization). The completion rate of staged surgery, interval between surgeries, future liver remnant (FLR) growth rate at 7 days after first-stage surgery, alanine transaminase (ALT) and aspartate transaminase (AST) levels at 5 days after fisrt-stage surgery, and postoperative complications (ascites, nausea, and vomiting, etc.) were compared between the groups. Results:The completion rate of staged surgery was 95.2% (40/42) in the observation group and 90.2% (37/41) in the control group ( χ2=0.62, P=0.431). The ALT and AST levels at 5 days after first-stage surgery were (550.4±86.0) U/L and (327.1±52.8) U/L in the observation group, respectively, which were significantly lower than those in the control group (861.6±106.3) U/L and (533.8±73.7) U/L, respectively ( t=13.13 and P<0.001, t=12.93 and P<0.001). The FLR growth rate were higher in the observation group than that in the control group [(80.4±10.3)% vs (49.3±5.7)%; t=13.13, P<0.001] and the interval between procedures were also shorter in the observation group (10.9±2.1 vs 22.4±4.8, d; t=9.65, P<0.001). The intraoperative blood loss of the first-stage surgery was lower in the observation group than that in the control group (350.5±45.2 vs 825.5±21.7, ml; t=21.43, P<0.001). The total complication rates after the first-stage surgery were 11.9% (5/42) in the observation group and 19.5% (8/41) in the control group, while after the second-stage surgery, the complication rates were 7.5% (3/40) and 18.9% (7/37), respectively, with no statistically significant differences ( χ2=0.65 and P=0.419, χ2=1.81 and 0.177, respectively). Conclusion:The modified ALPPS offers better postoperative liver function, reduced surgical trauma, accelerated FLR growth, and a shorter interval between procedures, demonstrating a favorable safety in the treatment of primary liver cancer.

Objective To evaluate the transition rules of normal body mass index(BMI),overweight and metabolic syndrome(MetS)in patients with major depressive disorder(MDD).Methods Patients with MDD who had multiple admission records between Jan 2016 and Nov 2021 in Beijing Anding Hospital,Capital Medical University were included.Based on the overweight and metabolic syndrome status assessed at each admission,the patients were categorized into three states:normal BMI,overweight and metabolic syndrome.A multi-state Markov model was used to analyze the transition intensity and transition frequency between three states and the influence of covariates on transitions.Results A total of 892 records of 398 subjects were included,with a median age of 56 years old and 31.4% males.The median follow-up period was 40 months.The multi-state model showed that there were 494 transitions between the three states,of which 5.1% moved from normal BMI to overweight and 5.5% moved from overweight to MetS.The intensity of transition was the highest from overweight to MetS,9.52 times greater than overweight to normal BMI.After 48.53 months,MDD patients with normal BMI began to transition to MetS.For overweight MDD patients,the transition to MetS started after 8.77 months.MDD patients with normal BMI or overweight had 31.4% and 50.4% probabilities of developing Mets after 36 months.For MDD patients comorbid with MetS,the probability of staying at MetS was 51.2% after 36 months.Multivariate analysis showed that being unmarried was a risk factor against developing overweight in normal BMI MDD patients,while a higher level of education was a protective factor against developing MetS in overweight MDD patients.Conclusion MDD patients exhibited a higher intensity and risk of developing MetS,and it is not easy to reverse MetS,suggesting that BMI management and MetS intervention should be strengthened in MDD patients.