Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

Spread through air spaces(STAS) represents a relatively novel concept in the pathology of lung cancer, specifically referring to the dissemination of tumor cells into the parenchymal air spaces adjacent to the primary tumor. Recognized by the World Health Organization(WHO) in 2015, STAS has been classified as a new invasive form of lung adenocarcinoma(ADC). Many studies have investigated the role of STAS, revealing its association not merely with the prognosis of ADC but also its influence on the outcomes of other malignant pulmonary neoplasms. Additionally, the underlying mechanisms and predictive models of STAS have received considerable attention in recent years. This paper provides a comprehensive overview of the research advancements and prospects of STAS, examining it from multiple perspectives.

OBJECTIVE To evaluate the cost-effectiveness of trastuzumab biosimilars （Hanquyou） versus original drug （Hesaiting） in the treatment of recurrent/metastatic human epidermal growth factor receptor-2 （HER-2） positive breast cancer. METHODS A partitional survival model was constructed based on the NCT03084237 trial data. The simulation period was 3 weeks， and the simulation time was 10 years. Using costs and quality-adjusted life year （QALY） as the output indicator， the cost- utility analysis method was used to evaluate the cost-effectiveness of the two schemes mentioned above. Univariate and probabilistic sensitivity analyses were performed to verify the robustness of the basic analysis. RESULTS The costs of the trastuzumab biosimilars group and original drug group were 111 516.72 yuan and 111 122.30 yuan respectively， with health utility values of 1.52 QALYs and 1.36 QALYs， and ICER of 2 465.12 yuan/QALY， which were less than 3 times China’s per capita gross domestic product （GDP） in 2023 as the threshold for willingness-to-pay （WTP） （268 200 yuan/QALY）. Univariate sensitivity analysis showed that the cost of the trastuzumab biosimilars and original drug had a great impact on the ICER. The probabilistic sensitivity analysis showed that the probability of trastuzumab biosimilars being cost-effective was 100% at WTP threshold of 14 902 yuan/QALY. CONCLUSIONS When WTP threshold is 3 times China’s GDP in 2023 （268 200 yuan/QALY）， compared with original drug， trastuzumab biosimilars have good cost-effectiveness in the treatment of recurrent/metastatic HER-2 positive breast cancer.

Perimenopausal syndrome （MPS）， a common endocrine system disease， is one of the diseases responding specifically to traditional Chinese medicine （TCM）. The China Association of Chinese Medicine organized experts in endocrinology， gynecology， and interdisciplinary fields of both Western and Chinese medicine to discuss the advantages and challenges of diagnosing and treating MPS with Western medicine， TCM， and integrative medicine. Experts at the conference believe that MPS is initiated by estrogen decline and rooted in deficiency， with the pathogenesis being imbalance between Yin and Yang in the kidney. The hormone replacement therapy in Western medicine for menopause can rapidly alleviate related symptoms by quickly restoring the estrogen level and timely detect and delay complications of menopause， whereas such a therapy has certain risks， necessitating close monitoring of adverse reactions. Moreover， the various contraindications and precautions limit the clinical application of the hormone replacement therapy. TCM has advantages in synergistically alleviating symptoms such as hot flashes， sweating， sleep disorders， and emotional abnormalities of MPS without causing obvious adverse reactions. However， its efficacy is slower than the hormone replacement therapy， and the TCM evidence for preventing and treating complications of menopause remains unclear. Three suggestions were proposed for the future development of both Western and TCM for ameliorating MPS. First， an integrated diagnosis and treatment system for MPS with both Western and Chinese medicine should be established. Second， high-quality evidence-based interventions for MPS should be developed with TCM alone or in combination with Western medicine. Third， efforts should be made to promote the new TCM drug development and the interdisciplinary cooperation for treating MPS.

The objective of this study was to observe the effect of Astragalus membranaceus on high sugar-induced Caenorhabditis elegans, and to explore its mechanism of action. UPLC-MS method was used to identify the components of Astragalus membranaceus. A high glucose model was established by using Caenorhabditis elegans as a model organism, and the effects of Astragalus membranaceus on body length, body bending, swallowing frequency, and reactive oxygen species (ROS) of the nematode were determined; the effects of Astragalus membranaceus on the expression of mRNA of genes related to the protein skinhead-1 (SKN-1) signaling pathway were examined by using the real-time fluorescence quantitative polymerase chain reaction (PCR). The results showed that compared with the normal group, the nematode body length, body bending, and swallowing frequency expression were significantly reduced and the ROS content in the body was significantly increased in the high glucose state; after the administration of Astragalus membranaceus, the body length, body bending, and swallowing frequency expression were significantly increased, and the ROS content was significantly reduced (P < 0.01). Compared with the normal group, SKN-1, superoxide dismutas-3 (SOD-3), glutathione S-transferase 4 (GST-4), and glutathione S-transferase 7 (GST-7) expression were significantly decreased in Caenorhabditis elegans in the high glucose condition; SKN-1, SOD-3, GST-4, and GST-7 expression were significantly increased after administration of Astragalus membranaceus (P < 0.01). In the present study, we demonstrated that Astragalus membranaceus has an effect on high glucose-induced Caenorhabditis elegans nematodes, and its mechanism of action may be through the modulation of the SKN-1 signaling pathwaym in order to ameliorate the oxidative stress response induced by high glucose.

Objective: To examine the clinical value of fluorescence-guided indocyanine green (ICG) laparoscopic anatomical hepatectomy in the treatment of primary hepatocellular carcinoma. Methods: Data from patients diagnosed with hepatocellular carcinoma and who underwent laparoscopic hepatectomy with ICG fluorescence navigation in the Department of Liver Surgery and Liver Transplantation Center of West China Hospital between September 2020 and May 2022 were retrospectively collected. There were 53 males and 19 females, with an age of (55.5±12.9)years(range:42.6 to 68.4 years). Among them, 13 of the cases underwent laparoscopic anatomical liver resection(LALR) guided by tans-arterial ICG,43 of the cases received LAIR guided by portal vein negative ICG, and 16 of the cases received LALR positive by portal vein. Comparison among the three groups was performed by one-way ANOVA; and the rank sum test was used for comparison between groups. The counting data was expressed as percentage,and the χ² test or Fisher's exact probability method was used for comparison between groups. Results: (1) Postoperative pathology: Resection R0 was achieved in all operations. The maximum tumor diameter of the patients in the arterial staining group, the reverse staining group, and the positive staining group(M (IQR)) was 2.5 (2.4) cm, 3.0 (2.5) cm and 3.0(2.4) cm,respectively. There were no statistically significant differences in the maximum tumor diameter between the three groups (P=0.364). The minimum tumor margin was 1.1 (1.1) cm, 1.0 (1.0) cm, 1.1 (1.6) cm in the the arterial staining group, reverse staining group and the positive staining group, respectively. There was no significant difference in the margin among the three groups (P=0.878). (2) Operation conditions: the operation time of the arterial staining group, the negative staining group, and the positive portal staining group was (348±93)minutes,(277±112)minutes,and (295±116)minutes,respectively. There were no significant differences in operation time among the three groups (P=0.134). The intraoperative blood loss of the three groups was 80(150)ml,200(350)ml,and 100(150)ml,respectively. There was no statistically significant difference in intraoperative bleeding volume between the three groups(P=0.743). All cases were not transfused during the operation and were not converted to laparotomy. ALT in the arterial staining group was higher than in the negative staining group in the first two days after the operation ((559±398)IU/L307(257) IU/L, q=235.5,P=0.004;(611±389)IU/L(331±242) IU/L, q=265.2, P=0.002). There was only one case of a grade III complication (Clavien-Dindo grading system) postoperative complication in the negative and positive staining group of the portal vein, respectively. Tumor markers in all patients decreased to the normal range after 2 months of operation. Conclusion: Laparoscopic anatomical hepatectomy guided by ICG fluorescence through arterial staining and portal vein staining is safe and feasible for primary hepatocellular carcinoma treatment.

Objective:To report our experience in using the Ilizarov technique to treat bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers.Methods:A retrospective study was performed to analyze the 19 patients with bone defects secondary to Gustilo Ⅲb open tibial fracture who had been treated at Department of Orthopaedics and Traumatology, Beijing Jishuitan Hospital between January of 2010 and June of 2021. They were 15 males and 4 females with an age of (41±11) years. Their inclusion criteria: undergoing treatment with Ilizarov technique (consecutive compression-distraction or bone transport), soft tissue coverage procedures resulting in wound closure and negative clinical infection signs for at least 3 months and normal serological inflammatory markers, and follow-up for more than 3 months after frame removal. Three-phase bone scan was performed for the patients before the present surgery. Debridement, sampling of deep tissues for bacterial culture, and external stabilization with a fixator were performed in the present surgery. Osteotomy for compression-distraction or bone transport technique was carried out at 1 stage or 2 stages. Systemic antibiotic therapy for 6 weeks was continued for those with positive microbiological analysis guided by antibiogram. Recorded were results of intra-operative pus detection around defects, microbiological findings, length of bone defect reconstructed, rate and time of infection recurrence during treatment, fracture union rate, bone healing index, bony and functional results.Results:The interval between primary injury to the present surgery was (10±8) months. The preoperative three-phase bone scan showed infection free in 8 cases, chronic osteomyelitis in 7 cases, and suspicious infection in 4 cases. No pus was found during intra-operative debridement in all. The intra-operative microbiological detection was positive in 1 sample in 1 patient (infection free indicated by bone scan), and in ≥2 samples in 3 patients (bone scan indicating non-infection, infection not excluded and osteomyelitis in 1 case each). The length of bone defect reconstructed was (8±3) cm. The follow-up after the present surgery was (37±15) months. Fracture union was achieved in all cases, with a bone healing index of (1.7±0.5) months/cm. Clinical infection signs were observed 1 (1, 1) month after the present surgery in 6 patients whose microbiological results were all negative. All the 6 patients ended up with no clinical recurrence after empirical use of systemic antibiotics in 5 and radical debridement in one. The bony results showed 16 excellent and 3 good cases while the functional results showed 10 excellent and 9 good cases.Conclusions:In treatment of bone defects secondary to Gustilo Ⅲb open tibial fractures with negative clinical signs and serological inflammatory markers, constant vigilance is needed against low-grade infection. Intra-operative multiple sampling of deep tissues with a standardized protocol and microbiological testing are extremely valuable for diagnosis of fracture-related infections.

Pulmonary hypertension (PH) is an insidious pulmonary vasculopathy with high mortality and morbidity and its underlying pathogenesis is still poorly delineated. The hyperproliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs) contributes to pulmonary vascular remodeling in pulmonary hypertension, which is closely linked to the downregulation of fork-head box transcriptional factor O1 (FoxO1) and apoptotic protein caspase 3 (Cas-3). Here, PA-targeted co-delivery of a FoxO1 stimulus (paclitaxel, PTX) and Cas-3 was exploited to alleviate monocrotaline-induced pulmonary hypertension. The co-delivery system is prepared by loading the active protein on paclitaxel-crystal nanoparticles, followed by a glucuronic acid coating to target the glucose transporter-1 on the PASMCs. The co-loaded system (170 nm) circulates in the blood over time, accumulates in the lung, effectively targets the PAs, and profoundly regresses the remodeling of pulmonary arteries and improves hemodynamics, leading to a decrease in pulmonary arterial pressure and Fulton's index. Our mechanistic studies suggest that the targeted co-delivery system alleviates experimental pulmonary hypertension primarily via the regression of PASMC proliferation by inhibiting cell cycle progression and promoting apoptosis. Taken together, this targeted co-delivery approach offers a promising avenue to target PAs and cure the intractable vasculopathy in pulmonary hypertension.

Objective: To establish and optimize a TaqMan-probe quantitative real-time PCR (qPCR) assay for the detection of 7 important Rickettsiales pathogens and simultaneous identification of the infection types. Methods: Based on the ompB gene of Rickettsia prowazekii, Rickettsia mooseri and spotted fever group rickettsiae, the groEL gene of Orientia tsutsugamushi, the 16S rRNA of Ehrlichia chaffeensis, the gltA gene of Anaplasma phagocytophilum and the com1 gene of Coxiella burnetii, we synthesized primers and TaqMan-probes and optimized the reaction system and reaction process to same solution. The sensitivity, specificity and reproducibility of this assay were evaluated and the assay was used for the detection of simulated and actual samples. Results: The Ct value of the standard curves of the 7 pathogens showed a good linear relationship with the number of DNA copies (all R² >0.990 0), the minimum detection limit was 10 copies/μl, showing good specificity. In the 96 tick nucleic acid extracts, Coxiella burnetii was detected in 1 sampleand spotted fever group Rickettsiae was detected in 3 samples. In the 80 blood samples from patients with undefined febrile illness, Orientia tsutsugamushi was detected in 1 sample and spotted fever group rickettsiae was detected in 2 samples. Conclusions: In this study, based on the established TaqMan-probe qPCR assay, the reaction system and reaction condition of the 7 important pathogens of Rickettsiales were optimized to the same solution. This method overcomes the shortcomings of using different reaction systems and reaction conditions for different pathogens, which can precisely identify the species of 7 important pathogens of Rickettsiales in clinical sample detections and is important for the infection type identification and laboratory detection time reduction to facilitate precise treatment of the patients.
Humans ; Rickettsiales ; Real-Time Polymerase Chain Reaction ; RNA, Ribosomal, 16S ; Reproducibility of Results ; Orientia tsutsugamushi ; Spotted Fever Group Rickettsiosis

Objective:To study the outcome of realignment for genu varum with tibial bone defect managed with antegrade bone transport.Methods:To retrospectively study 11 patients with tibial bone defect and genu varum treated with antegrade bone transport from January 2012 to December 2020. All the patients were males, aged 42±16 years, left in 8 cases and right in 3. The segmental bone defect was secondary to fractures with amount of 7.9±2.1 cm. 10 cases were congenital genu varus, and 1 case was genu varus caused by malunion of proximal tibial fracture. The anatomical lateral tibio-femoral angle (aLTFA) was 179°(178°, 180°), the anatomical lateral distal femoral angle (aLDFA) was 82°(81°, 83°), joint line convergence angle (JLCA) was 0°(0°, 1°) and the anatomical medial proximal tibial angle (aMPTA) was 83.1°±3.9° before treatment. 7 cases were treated with unilateral external fixators, 3 cases with circular external fixators, and 1 case with hybrid external fixator. Antegrade bone transport surgeries were performed to treat bone defects and varus deformities. Among them, 3 cases using unilateral external fixators were additionally corrected for varus using swinging clamps, while 1 case using a circular external fixator was corrected for varus by installing hinges on the lateral side of the proximal tibia and distracting the medial-positioned threaded rod. The data including the angles between proximal pins in monorail fixators or proximal ring orientation in ring fixators and knee joint line, post-operative mechanic axis deviation (MAD) of lower extremity, the position of the mechanical axis relative to the width of the tibial plateau, mechanic medial proximal tibial angle (mMPTA), the amount of deformity correction in radiographic AP view, bone healing time, bone healing index (BHI), functional score and complications according to Paley's criteria were studied.Results:All 11 patients were followed up, and the follow-up time after removing the external fixators was 11(3, 25) months. The angles between pins in proximal clamp in monorail frame of 7 cases and hybrid frame of 1 case and joint line were 0° (-1°, 1°), while those between proximal ring orientation in circular fixators of 3 cases and joint line were 0°, 0° and 2° respectively. The MAD were -6±6 mm, mMPTA was 90°(89°, 92°), the amount of correction was 7.2°±3.9° in the last follow-up. The final mechanic axis passed through the lateral plateau at 58%±9% of its width (counting from medial knee edge). Well consolidation was achieved for all patients with 12±4 months (range, 7-20 months) of bone healing time. BHI was 1.6±0.6 months/cm (range, 1.2-2.9 months/cm). Functional score according to Paley's criteria was excellent in 7 cases and good in 4. Complications were 5 problems (3 of pin site infections and 2 of soft tissue infections) and 1 obstacle (soft tissue invagination). All the cases with problems were resolved with oral antibiotics. In the one with the obstacle of soft tissue invagination, the skin and docking site bone healing were noticed after invaginated tissue resection and refreshment procedure.Conclusion:It is advisable for genu varum with tibial bone defect to be realigned while managed with antegrade bone transport.