Based on Professor YANG Zhen's theory of "qi dynamics of ministerial fire"， this paper systematically elucidates the pathogenesis of jueyin （厥阴） disease and the clinical rationale for applying Wumei Pill （乌梅丸）. Jueyin disease is characterized by dysfunction of the middle earth in regulating qi dynamics and disruption of the pivot mechanism， leading to an upward disturbance of ministerial fire and an underlying pattern of deficiency-cold of true yang， thereby forming a state of cold and heat in complexity. Wumei Pill fully exerts the synergistic effects of sour-astringency， bitter-descending， and acrid-warm medicinals， reflecting the therapeutic principle of regulating the pivot mechanism and restraining the upward rebellion of ministerial fire， with the aim of returning fire to its source and restoring the circulation of qi. Based on the four-dimensional pathological evolution of Jueyin disease， namely disorder of pivot qi harmonization， failure of ying （营）-blood nourishment and containment， loss of yin sustenance and balance， and instabi-lity of ministerial fire， the paper systematically reveals the underlying logic of Wumei Pill in treating different diseases with the same therapeutic principle. In addition， a clinical case of hemoptysis treated with modified Wumei Pill is presented， providing insights into its formulation principles and expanding its application in complex and refractory multi-system diseases.

Based on Professor YANG Zhen's theory of "qi dynamics of ministerial fire"， this paper systematically elucidates the pathogenesis of jueyin （厥阴） disease and the clinical rationale for applying Wumei Pill （乌梅丸）. Jueyin disease is characterized by dysfunction of the middle earth in regulating qi dynamics and disruption of the pivot mechanism， leading to an upward disturbance of ministerial fire and an underlying pattern of deficiency-cold of true yang， thereby forming a state of cold and heat in complexity. Wumei Pill fully exerts the synergistic effects of sour-astringency， bitter-descending， and acrid-warm medicinals， reflecting the therapeutic principle of regulating the pivot mechanism and restraining the upward rebellion of ministerial fire， with the aim of returning fire to its source and restoring the circulation of qi. Based on the four-dimensional pathological evolution of Jueyin disease， namely disorder of pivot qi harmonization， failure of ying （营）-blood nourishment and containment， loss of yin sustenance and balance， and instabi-lity of ministerial fire， the paper systematically reveals the underlying logic of Wumei Pill in treating different diseases with the same therapeutic principle. In addition， a clinical case of hemoptysis treated with modified Wumei Pill is presented， providing insights into its formulation principles and expanding its application in complex and refractory multi-system diseases.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective:To compare gamma pass rates for ultra-long target volumes of cervical cancer between individual measurements by moving the phantom isocenter and segmented measurements combined with merging and to assess the influence of scattering blocks on verification result during segmented measurements.Methods:A retrospective study was conducted on 24 cervical cancer patients with ultra-long target volumes (lengths: 23.5–36.0 cm) treated using helical tomotherapy. Two measurement methods were used to verify the gamma pass rates: individual measurements by moving the phantom isocenter and segmented measurements combined with merging. For the first measurement method, the patients′ treatment plans were transferred to the ArcCheck phantom. After the dose distribution was calculated and exported, the gamma pass rates measured and calculated were compared. For the segmented measurements, a 50-cm-long virtual phantom was imported, and the treatment plans of patients were then transferred to the virtual phantom. Afterward, the dose distribution of the virtual phantom was calculated and exported. Then, two dose measurements were conducted under upward and downward setup of the ArcCheck phantom. Two dose measurement files were obtained and then fused to produce a merged file. Then, the γ pass rates were calculated. Repeated measurements were conducted after scattering blocks were installed. The γ-pass rates were assessed using varying dose criteria.Results:Under various evaluation criteria, no statistically significant differences in γ pass rates were observed between the individual measurements by moving the phantom isocenter and the segmented measurement in the presence of scattering blocks ( P > 0.05). In contrast, there existed statistically significant differences in γ pass rates between the individual measurements by moving the phantom isocenter and the segmented measurement in the absence of scattering blocks according to the (global) criterion of 3%/2 mm absolute dose ( Z = -2.31, P = 0.02). Additionally, the segmented measurement in the presence of scattering blocks enhanced pass rates, with statistical significant difference under the criterion of 3%/2 mm relative dose ( Z = -2.11, P = 0.04). Conclusions:In the case where ArcCheck is used to measure the dose distribution of ultra-long target volumes in cervical cancer, it is advisable to preferentially use individual measurements by moving the phantom isocenter. When segmented measurements combined with merging are required, it is necessary to install scattering blocks during measurements. This will improve γ-pass rates during verification and ensure the accuracy of dose verification.

OBJECTIVE To compare the clinical efficacy and safety of remimazolam and propofol in general anesthesia induction and maintenance for elderly patients undergoing thoracoscopic lobectomy. METHODS A total of 86 elderly lung cancer patients who underwent thoracoscopic lobectomy at Chongqing University Three Gorges Hospital from February to July 2024 were selected and divided into the propofol group and the remimazolam group according to the randomized numerical table method， with 43 cases in each group. During anesthesia induction， patients in the propofol group and the remimazolam group were intravenously administered 2 mg/kg of Propofol medium- and long-chain fat emulsion injection or 0.25 mg/kg of Remimazolam tosilate for injection， respectively； during anesthesia maintenance， the two groups received intravenous infusion of 6-10 mg/（kg·h） of Propofol medium- and long- chain fat emulsion injection or 1-3 mg/（kg·h） of Remimazolam tosilate for injection， respectively. The anesthesia effects， anesthesia-related indicators， intraoperative opioid and muscle relaxant dosages， Ramsay sedation score， numerical rating scale （NRS） score， and hemodynamic parameters were compared between the two groups， and the occurrence of adverse drug reactions was recorded. RESULTS A total of 41 patients in the propofol group and 43 patients in the remimazolam group completed the trial. The proportion of patients with grade Ⅰ anesthesia effect in the remimazolam group was significantly higher than that in the propofol group， while the proportion of patients with grade Ⅱ anesthesia effect was significantly lower than that in the propofol group （P＜0.05）. In this group， the disappearance time of eyelash reflex， the time taken for the bispectral index to drop to 60， and the Ramsay sedation scores （2 and 6 hours after operation） were all significantly prolonged or increased， while the recovery time， NRS scores （2 and 6 hours after operation）， and the incidence of intraoperative hypotension were all significantly shortened or reduced； moreover， the improvements of the above sedation/NRS scores exhibited a time-dependent pattern within 2 to 24 hours after operation （P＜0.05）. Compared with before anesthesia induction （T0）， the heart rate [except at 2 min after medication （T1）， 60 min after anesthesia （T4）， and at the end of surgery （T5） in the remimazolam group] and mean arterial pressure [except at T1 in the remimazolam group] of patients in both groups significantly decreased at T1， 5 min after medication （T2）， at the start of surgery （T3）， T4， and T5 （P＜0.05）. Meanwhile， regional cerebral oxygen saturation significantly increased in both groups. Furthermore， the heart rate and mean arterial pressure of patients in the remimazolam group were significantly higher than those in the propofol group at T1， T2 and T4 （P＜0.05）. No statistically significant differences were observed between the two groups in terms of postanesthesia care unit stay time， dosage of opioids and muscle relaxants， regional cerebral oxygen saturation， or peripheral oxygen saturation at various time points （P＞0.05）. CONCLUSIONS Compared to propofol， remimazolam demonstrates superior anesthesia effects when used for the induction and maintenance of general anesthesia in elderly patients undergoing thoracoscopic lobectomy. It not only provides more stable intraoperative hemodynamics and shortens the postoperative recovery time but also effectively reduces the incidence of intraoperative hypotension.

Objective:To compare gamma pass rates for ultra-long target volumes of cervical cancer between individual measurements by moving the phantom isocenter and segmented measurements combined with merging and to assess the influence of scattering blocks on verification result during segmented measurements.Methods:A retrospective study was conducted on 24 cervical cancer patients with ultra-long target volumes (lengths: 23.5–36.0 cm) treated using helical tomotherapy. Two measurement methods were used to verify the gamma pass rates: individual measurements by moving the phantom isocenter and segmented measurements combined with merging. For the first measurement method, the patients′ treatment plans were transferred to the ArcCheck phantom. After the dose distribution was calculated and exported, the gamma pass rates measured and calculated were compared. For the segmented measurements, a 50-cm-long virtual phantom was imported, and the treatment plans of patients were then transferred to the virtual phantom. Afterward, the dose distribution of the virtual phantom was calculated and exported. Then, two dose measurements were conducted under upward and downward setup of the ArcCheck phantom. Two dose measurement files were obtained and then fused to produce a merged file. Then, the γ pass rates were calculated. Repeated measurements were conducted after scattering blocks were installed. The γ-pass rates were assessed using varying dose criteria.Results:Under various evaluation criteria, no statistically significant differences in γ pass rates were observed between the individual measurements by moving the phantom isocenter and the segmented measurement in the presence of scattering blocks ( P > 0.05). In contrast, there existed statistically significant differences in γ pass rates between the individual measurements by moving the phantom isocenter and the segmented measurement in the absence of scattering blocks according to the (global) criterion of 3%/2 mm absolute dose ( Z = -2.31, P = 0.02). Additionally, the segmented measurement in the presence of scattering blocks enhanced pass rates, with statistical significant difference under the criterion of 3%/2 mm relative dose ( Z = -2.11, P = 0.04). Conclusions:In the case where ArcCheck is used to measure the dose distribution of ultra-long target volumes in cervical cancer, it is advisable to preferentially use individual measurements by moving the phantom isocenter. When segmented measurements combined with merging are required, it is necessary to install scattering blocks during measurements. This will improve γ-pass rates during verification and ensure the accuracy of dose verification.

Objective::This study aimed to elucidate the effect of the lipopolysaccharides/toll-like receptor 4 (LPS/TLR4) pathway on early atherosclerosis (AS) development and its associated changes in fecal metabolites, thereby providing an experimental foundation for strategies to prevent and treat early AS.Methods::Twelve Tibetan miniature pigs aged 4-5 months were divided into normal control (NC) group and AS group (6 pigs in each). The group assignment was primarily based on body weight; Secondary criteria, including glucose, lipid profiles, and inflammatory indices, were considered to ensure balanced baseline characteristics between the 2 groups (all P > 0.05). AS group received a high-fat diet for 16 weeks to establish an AS model, while the NC group received a normal diet. Subsequently, serum levels of lipids and various inflammation and oxidative stress markers were measured. Pathological changes in the aorta and colon tissue, LPS/TLR4 pathway-associated protein expressions in the aorta, as well as occludin and zonula occludens-1 in the colon were also assessed. Proton nuclear magnetic resonance spectra technology was employed for the metabolomic analysis of fecal extracts. Results::The lipid metabolism was disrupted in AS group, with significantly higher total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels ((12.24 ± 5.24) mmol/L vs. (1.86 ± 0.27) mmol/L, P = 0.004,6; (2.39 ± 0.50) mmol/L vs. (0.83 ± 0.07) mmol/L, P = 0.000,5; (6.94 ± 2.87) mmol/L vs. (0.77 ± 0.18) mmol/L, P = 0.003,3), as compared to that in NC group. Serum factors, including LPS, tumor necrosis factor-α, and malondialdehyde levels of AS group were significantly higher than that of NC group ((1,230.00 ± 192.70) EU/L vs. (695.70 ± 213.70) EU/L), P = 0.001,1; (424.20 ± 176.90) ng/L vs. (51.20 ± 26.61) ng/L, P = 0.023,5; (3.60 ± 0.77) nmol/mL vs. (2.62 ± 0.21) nmol/mL, P = 0.025,4). Pathological evaluations revealed prominent lipid deposition area in the aortic arch, thoracic aorta, and abdominal aorta of the AS group compared with that of the NC group (4.17% ± 2.30% vs. 0, P = 0.006,7; 6.23% ± 2.95% vs. 0, P = 0.003,6; 3.78% ± 2.18% vs. 0, P = 0.008,1). TLR4, nuclear factor kappa-B p65, and tumor necrosis factor-α expression in the aorta tissue of the AS group were upregulated, whereas occludin and zonula occludens-1 expression in colon tissues was downregulated. Additionally, metabolomics identified significant differences in 21 metabolites in the feces of the AS group compared to the NC group, with further analysis linking these differences to amino acid metabolism. Conclusions::The Tibetan miniature pig model of early AS induced by high-fat intake displayed pronounced chronic inflammation. Preliminary findings suggest that the underlying mechanisms may be associated with the LPS/TLR4 pathway and intestinal metabolic disorders.

Objective: The phase 2, open-label, randomized, 3-arm study (NCT03776812) found that intermittently dosed relacorilant + nab-paclitaxel improved progression-free survival, duration of response, and overall survival compared with nab-paclitaxel monotherapy with minimal additional toxicity. This study analyzed the cost-effectiveness of intermittent relacorilant + nab-paclitaxel (IN), continuous relacorilant + nab-paclitaxel (CN) and nabpaclitaxel monotherapy (N) from the payer’s perspective over a 5-year time horizon. Methods: The health outcome is expressed in quality-adjusted life years (QALYs). IN, CN and N were evaluated using QALYs and incremental cost-effectiveness ratio (ICER). The data for this model come from the NCT03776812 trial and other published literature. The impact of the variables is studied using a one-way deterministic sensitivity analysis and a probabilistic sensitivity analysis based on a second-order Monte Carlo simulation. Results: N was the least costly strategy, at $ 4606.05, followed by IN ($22,597.75) and CN ($44,276.86). Based on a willingness-to-pay threshold of $100,000/QALY, IN was costeffective compared with N, with an ICER of $21,418.69 per QALY gained for N, whereas CN was ruled out by extended dominance (less effective, more costly), compared with N. The incremental benefits of IN compared to CN and N were 0.72 QALYs and 0.84 QALYs. Conclusion From a US health care system perspective, IN may be cost-effective compared to CN for patients with recurrent platinum-resistant ovarian cancer, and IN is also better than CN and N in terms of efficacy. Therefore, IN is a high-quality regimen for clinicians to treat patients with recurrent platinum-resistant ovarian cancer.

Objectives::The aim of this multicenter, prospective, single-arm pilot study (ClinicalTrials.gov number: NCT05040074) was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system, SQ-Kyrin ?-M Clip (Shenqi Medical, Shanghai, China), in patients with severe mitral regurgitation (MR). Methods::The heart team considered patients from 5 centers in China with clinically significant functional mitral regurgitation ≥3+ despite optimal medical therapy or degenerative mitral regurgitation ≥3+ with high surgical risk as candidates for transcatheter repair. All patients received transcatheter edge-to-edge mitral valve repair under general anesthesia. The primary outcome was technical success, which included all of the following measured at the exit from the catheterization laboratory: (1) absence of procedural mortality; (2) successful access, delivery, and retrieval of the device delivery system; (3) successful deployment and correct positioning of the first intended device; and (4) no emergency surgery or reintervention related to the device or access procedure. The secondary outcomes included all-cause mortality, serious adverse events, device success, and procedural success 30 d after the intervention.Results::From June 2021 to December 2021, 18 patients were enrolled in this study with age (75.7 ± 7.4) years. Fifteen patients had MR 4+, while 3 had MR 3+. Technical success was achieved in all patients, including 6 degenerative mitral regurgitation and 12 functional mitral regurgitation patients. There was no all-cause mortality at 30 d. One patient had single leaflet device attachment within 30 d, which was regarded as a serious adverse event, and the patient was successfully treated with reintervention by implanting another clip. Another patient’s transmitral gradient was 6 mmHg (>5 mmHg), with an effective orifice area of 2.57 cm 2 after the procedure. Sixteen patients had device success and procedural success at 30 d postoperation. Fourteen patients had MR 1+, 3 had MR 2+, and only 1 patient had MR 3 + 30 d after the procedure. Conclusions::The results of this feasibility study showed the efficacy and safety of the SQ-Kyrin ?-M device in the Chinese population with severe MR, laying a solid foundation for a subsequent large-scale confirmatory study.

Objective To investigate the mechanism of cartilage injury and inflammation in the WHBE rabbit KOA model and the effect of platelet-rich fibrin releasates(PRFr)treatment on the KOA process,we established a WHBE rabbit KOA model by excision of medial collateral and partial patellar ligaments and administered a PRFr solution.Methods Twenty-four WHBE rabbits were randomly divided into three groups:normal control(NC)group(n=6),model(KOA)group(n=12),and cure(PRFr)group(n=6).KOA and PRFr groups were injected with 0.5 mL saline and PRFr into both joint cavities on 7 and 14 postoperative days,respectively.At 4 and 8 weeks of modeling,the knee joint grade scoring,X-ray imaging,and gross scoring were performed.Serum levels of IL-1β,TNF-α,and MMP-13 were measured by ELISA.At 4 weeks,6 animals in the KOA group were euthanized,and at 8 weeks,the remaining animals in each group were euthanized.Pathological sections were prepared after decalcification,and then HE,toluidine blue,and safranin O-fast green staining and immunohistochemical analysis of TGF-β,BMP3,and NF-κB were conducted.Results The Lequesne MG behavioral score,Mankin's score,and Pelletier score of WHBE rabbits after the operation were significantly increased compared with the NC group(P＜0.01).Pathological observations revealed surface defects of the cartilage and partial loss of chondrocytes.These result indicated that the KOA model was established successfully.In KOA rabbits,knee joint swelling,joint pain stimulation,and movement limitation were obvious.X-rays showed a high-density soft tissue shadow,indicating more joint effusion and a rough articular surface in general.After PRFr treatment,the serum levels of proinflammatory factors IL-1β,TNF-α,and MMP-13 in KOA model rabbits were significantly reversed(P＜0.05,P＜0.01).Additionally,the cartilage surface became smooth,and most chondrocytes were neatly distributed.Expression levels of TGF-β,BMP3,and NF-κB induced by KOA were also significantly decreased(P＜0.01).Conclusions We successfully established a KOA model in WHBE rabbits,and PRFr improved the cartilage injury and inflammation of the WHBE rabbit KOA model through TGF-β/BMP and NF-κB pathways.