This paper explores the therapeutic approach for glaucoma based on the concept of "jueyin （厥阴） as the closing phase" from the perspectives of time and space. In traditional Chinese medicine， jueyin governs inward， converging aspect of qi， representing the crucial turning point between the end of yin and the emergence of yang， as well as the transformation between yin and yang. When the closing and descending function of jueyin operates smoothly， it promotes the inward convergence and smooth descent of qi， enabling the internal retention of blood， spirit， and emotions， which nourishes the internal organs and moistens the meridian-sinews. Conversely， dysfunction of this "closing" mechanism results in a disturbance of yin and yang， a mixture of cold and heat， and disharmony of qi and blood. It is proposed that "failure of jueyin to properly close and descend" is a core pathomechanism of glaucoma. From the perspective of spatiotemporal theory， clinical treatment should focus on "regulating the closing function of jueyin and harmonizing yin and yang". The modified Wumei Pill （乌梅丸） is recommended to adjust the ascending-descending and entering-exiting dynamics of jueyin qi transformation， thereby restoring its free flow， achieving yin and yang balance， and ensuring nourishment to the ocular system.

Increasing evidence showed that histone deacetylase 6 (HDAC6) dysfunction is directly associated with the onset and progression of various diseases, especially cancers, making the development of HDAC6-targeted anti-tumor agents a research hotspot. In this study, artificial intelligence (AI) technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline, which combined Voting strategy based on compound-protein interaction (CPI) prediction models, cascade molecular docking, and molecular dynamic (MD) simulations. The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays. Among the identified compounds, Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity (IC₅₀ = 5.41 nM) than that of tubastatin A (TubA) (IC₅₀ = 15.11 nM), along with a favorable subtype selectivity profile (selectivity index ≈ 117.23 for HDAC1), which was further verified by the Western blot analysis. Additionally, Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells, exerting desirable antiproliferative activity (IC₅₀ = 2.59 μM). Furthermore, based on long-term MD simulation trajectory, the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis, thereby elucidating its binding mechanism. Moreover, the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation, thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.

Ketone bodies have beneficial metabolic activities, and the induction of plasma ketone bodies is a health promotion strategy. Dietary supplementation of sodium butyrate (SB) is an effective approach in the induction of plasma ketone bodies. However, the cellular and molecular mechanisms are unknown. In this study, SB was found to enhance the catalytic activity of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), a rate-limiting enzyme in ketogenesis, to promote ketone body production in hepatocytes. SB administrated by gavage or intraperitoneal injection significantly induced blood ß-hydroxybutyrate (BHB) in mice. BHB production was induced in the primary hepatocytes by SB. Protein succinylation was altered by SB in the liver tissues with down-regulation in 58 proteins and up-regulation in 26 proteins in the proteomics analysis. However, the alteration was mostly observed in mitochondrial proteins with 41% down- and 65% up-regulation, respectively. Succinylation status of HMGCS2 protein was altered by a reduction at two sites (K221 and K358) without a change in the protein level. The SB effect was significantly reduced by a SIRT5 inhibitor and in Sirt5-KO mice. The data suggests that SB activated HMGCS2 through SIRT5-mediated desuccinylation for ketone body production by the liver. The effect was not associated with an elevation in NAD⁺/NADH ratio according to our metabolomics analysis. The data provide a novel molecular mechanism for SB activity in the induction of ketone body production.
Mice ; Animals ; Butyric Acid/metabolism* ; Ketone Bodies/metabolism* ; Liver/metabolism* ; Hydroxybutyrates/metabolism* ; Down-Regulation ; Sirtuins/metabolism* ; Hydroxymethylglutaryl-CoA Synthase/metabolism*

Objective:To review the clinical efficacy and safety of the FOLFIRINOX (oxaliplatin, irinotecan, leucovorin, fluorouracil) regimen in treatment of pancreatic cancer.Methods:The clinical data of 31 patients with pancreatic cancer who were treated with the FOLFIRINOX regimen from July 2016 to December 2019 at the Department of General Surgery, China-Japan Friendship Hospital were retrospectively analyzed. For the 20 males and 11 females who were enrolled into this study, their age ranged from 29 to 80 years (mean 56.9 years). The FOLFIRINOX regimen was used as neoadjuvant therapy in 12 patients, postoperative therapy in 10 patients with liver-metastases, and postoperative adjuvant therapy in 9 patients (as second-line chemotherapy in 7 patients and as first-line chemotherapy in 2 patients). The clinical efficacy and adverse reactions of chemotherapy were evaluated.Results:In this study, 8 patients received the modified FOLFIRINOX regimen. Of the remaining 23 patients who received the standard FOLFIRINOX regimen, 10 (43.3%) were converted to the modified regimen because of adverse events. On clinical efficacy evaluation after neoadjuvant therapy: 5 patients achieved partial remission (PR), 3 stable disease (SD) and 4 progression disease (PD). The disease control rate (DCR) was 66.7% (8/12). For 10 patients got remission of abdominal pain, 5 patients underwent surgical resection. For the 10 patients with liver-metastases, 6 achieved PR, 1 SD, 3 PD. For 7 patients got disease control. For 8 patients had remission of abdominal pain, 1 patient underwent surgical resection. For the 7 patients who received second-line chemotherapy, 2 achieved PR and 5 PD. No tumor recurrence or metastases were found in the two patients after the first-line chemotherapy. Adverse events above grade three in all the patients included neutropenia in 12 patients (38.7%), leukopenia in 7 patients (22.6%) and thrombocytopenia in 1 patient (3.2%).Conclusions:The FOLFIRINOX regimen was efficacious with a high DCR rate and controllable adverse events. Balancing its efficacy and safety showed this regimen to be beneficial to patients with pancreatic cancer.

Objective:To evaluate the accuracy of pRIFLE criterion and KDIGO criterion for the diagnosis of acute kidney injury (AKI) after radical operations for tetralogy of Fallot in children from the perspective of postoperative outcomes.Methods:A total of 375 children, aged<8 yr, undergoing radical operations for tetralogy of Fallot, were selected continuously and retrospectively. According to the pRIFLE and KDIGO diagnostic criteria, postoperative AKI was diagnosed, and the children were classified into different AKI grades. The prognostic parameters (postoperative mechanical ventilation time, duration of intensive care unit (ICU) stay, postoperative length of hospital stay, total costs of hospitalization, and in-hospital mortality, etc.) were collected, and the differences among different AKI grades were compared. Logistic regression method was used to analyze the risk factors for prolonged postoperative length of hospital stay (≥14 days) when two different criteria were used to diagnose AKI. The children diagnosed as non-AKI by KDIGO criterion were further confirmed using pRIFLE criterion, and the prognostic parameters in the children who were diagnosed as AKI and non-AKI were compared.Results:When two different criteria were used to diagnose AKI after radical resection for tetralogy of Fallot, the incidence was 56.8% (pRIFLE criterion) and 40.0% (KDIGO criterion). AKI diagnosed according to the two criteria was the independent risk factor for prolonged postoperative length of hospital stay, and the levels of all the prognostic parameters (postoperative mechanical ventilation time, duration of ICU stay, postoperative length of hospital stay, total costs of hospitalization, and in-hospital mortality) were significantly higher in AKI children than in non-AKI (AKI grade 0) children ( P<0.01). Among the 225 children diagnosed as non-AKI according to the KDIGO criterion, 63 cases were diagnosed as AKI and 162 cases as non-AKI according to the pRIFLE criterion, however, there was no significant difference in each prognostic parameter between children with AKI and non-AKI ( P>0.05). Conclusion:The pRIFLE criterion has a higher sensitivity, while the KDIGO criterion produces better accuracy when used to evaluate the diagnosis of AKI after radical operation for tetralogy of Fallot in children from the perspective of postoperative outcomes.

Objective To summarize the experience of surgical treatments for giant liver hemangioma.Methods A retrospective study was made on the clinical data of patients with liver hemangioma larger than 10 cm in diameter,which were divided into two groups (10-＜ 20 cm,88 cases,≥ 20 cm,31 cases).Data included age and gender,presentation,treatment methods,peri-operative indexes,and complications.Results All patients complained symptoms,the average diameter was (16 ± 7) cm.There were 23,7,and 17 cases respectively with anemia,thrombocytopenia and hypofibrinogenemia,all were more often seen in ≥20 cm group (P ＜ 0.001).Five patients were diagnosed as Kasabach-Merritt syndrome in ≥20 cm group.Patients in ≥20 cm group also had greater rates of compression of the porta hepatis (P ＜ 0.001).Patients in ≥ 20 cm group were treated more often by hepatic resections,while enucleations was often done in 10-＜20 cm group.The ≥20 cm group had more blood loss (P ＜0.001)and autologous transfusion (P ＜ 0.001),greater rates of blood transfusion (P ＜ 0.001).There was no significant difference on morbidity between the two groups (P =0.194).Conclusions For giant liver hemangioma both enucleation and hepatic resection could be completed safely in experienced hands.

Objective To analyze the safety and clinical effects of laparoscopic partial splenectomy for splenic solid benign lesions.Methods Retrospective analysis was made on patients with splenic solid benign tumor admitted from Jan 2015 to Feb 2017.Results 6 patients (4 males,2 females) underwent successful partial splenectomy for splenic tumors.Mean patient age was 44.7 years (range,28-58 years).5 patients were diagnosed by wellness examinations,1 patient had abdominal discomfort.The diameter of tumors ranged from 5.0 to 8.3 cm.Tumors were located in the superior lobes in 2 cases and the others were located in the inferior lobes.The operation times were 120-240 min and intraoperative blood loss was 50-1 400 ml (mean,375 ml).Laparoscopic procedure was successful in all patients without major complications.Postoperative pathology showed hemangioma in 5 cases and hemangioendothelioma in one patient.After 3 to 28 months follow-up no patients experienced recurrence.Conclusions Laparoscopic partial splenectomy is safe and effective in patients with focal benign splenic lesion that was located at the edge of the spleen or in the upper or lower pole of the spleen.

Objective To analyze the clinical experience of laparoscopic surgery for giant liver hemangiomas.Methods The clinical data of 40 patients who underwent laparoscopic surgery for giant liver hemangiomas from August 2012 to January 2018 in the China-Japan Friendship Hospital were retrospectively analyzed.The diameters of the liver hemangiomas were more than 10 cm for all the patients.The liver functions of all the patients were Child-Pugh class A.The follow-up was up to the end of February 2018.Results Laparoscopic treatment of giant liver hemangioma was successfully performed in 37 patients.Three patients were converted to open hepatectomy.The mean diameter of the giant liver hemangiomas was (10.8± 1.3) cm (ranged 10.0～15.0 cm).The mean operative time for laparoscopic therapy was (154.7±68.0) min (range 70～ 390 min).The mean intraoperative blood loss was 200 (100 ～ 400) ml.20 patients received autologous blood transfusion.Of these 2 patients received in addition allogeneic blood transfusion.The postoperative hospital stay was (6.9t2.0) days (range 4～14 days).Postoperative complications occurred in 3 patients (8.1％).Two patients developed postoperative pleural effusion and one pelvic effusion.Two patients responded well to puncture drainage and one to conservation management.There was no postoperative hemorrhage,bile leakage or air embolism.All patients were followed-up and no liver hemangioma recurrence was detected.Conclusion Laparoscopic surgery was a safe and efficacious procedure in selected patients with giant liver hemangioma.

Objective To investigate the role of GABAAα3and GABAB receptors in the ventrolateral periaqueductal gray in the development of paw acute pain in rats.Methods Twelve male SD rats, weighing 280~320 g, were randomly divided into two groups: normal saline group (group NS), formaldehyde-induced pain group (group F), 6 rats in each group.In group F, rats were subcutaneously injected with 2% formaldehyde 50 μl into the ventral surface of right hind paw to induce periphery inflammatory pain.In group NS, rats were subcutaneously injected with normal saline into the ventral surface of right hind paw.Mechanical threshold was assessed using von Frey hairs for every ten minutes.The rat pain behavior scores were recorded for every five minutes.The thickness of skin and skin temperature were recorded for every fifteen minutes.Results Mechanical hyperalgesia were induced in group F after formalin injection into right hind paw.Compared with group NS, rat pain behavior scores were increased significantly in group F at all time points after injection, mechanical threshold were decreased significantly in group F at 10-60 min after injection, the temperature of the skin and the skin thickness were increased significantly in group F at 15-60 min after injection (P<0.05), the levels of the expression of GABAAα3 and GABAB were significantly increased in group F (P<0.05).Conclusion GABAAα3and GABAB receptors mediates formalin-induced hyperalgesia at ventrolateral portion of the PAG (vlPAG) of rats.

Objective To analyze the differences between benign and potential malignant small pancreatic cystic lesions.Methods We retrospectively analyzed the clinical and pathological data of asymptomatic patients with pancreatic small cystic lesions and divided them into benign group (including serous cystic neoplasms,lymphoepithelial cyst and pseudocyst) and potential malignant group (including mucinous cystic neoplasms,intraductal papillary mucinous neoplasms and solid pseudopapillary neoplasms).Comparison of clinical data was made between the two groups.Results 46 patients with pathological results were included (22 cases in benign group and 24 cases in potential malignant group).No difference was detected on demographic data and lab results between the two groups.Compared with benign patients,patients in the potential malignant group were more likely to show thicken wall (P =0.000),mural nodule (P =0.000),solid constituents inside the cyst (P =0.001),wall enhancement (P =0.003) and uneven wall on CT scan (P =0.024).The diagnostic sensitivity,specificity and accuracy of the combination of above mentioned CT features for potential malignant diseases were 91.7％,77.3％ and 84.8％,respectively.Conclusions Pancreatic cystic lesions with thicken wall,mural nodule,wall enhancement,solid parts inside the cyst and uneven wall on CT were more likely of potential malignant entities.