Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective:To establish a lumbosacral triangle (composed of L 5 transverse process, S 1 superior articular process, sacral ala and iliac crest) classification and to guide L 5S 1 endoscopic surgery. Methods:A total of 647 patients with low back pain who admitted to Tianjin Hospital from January 2016 to October 2018 were retrospectively analyzed, including 315 males and 332 females, aged 42.9±15.1 years (range, 19-74 years). The L 5 transverse process sacral distance (TSD), inter trans-verse process length (ITL), interlaminar width (ILW), interlaminar height (ILH), iliosacral angle (ISA), iliac crest height (IH), intervertebral space height (ISH), intervertebral foramen height (IFH), and intervertebral foramen width (IFW) were measured based on lumbar spine anterior-posterior and lateral radiographs. Spearman correlation analysis and hierarchical cluster analysis were used to establish the lumbosacral triangle classification. A total of 822 patients underwent endoscopic L 5S 1 surgery based on lumbosacral triangle classification guidance and verification in Tianjin Hospital from January 2020 to December 2022, including 421 males and 401 females, aged 45.1±16.7 years (range, 15-79 years). The visual analogue scale (VAS) and Oswestry disability index (ODI) were compared before and after surgery, and the Macnab criteria were used to assess surgical outcomes. Results:Spearman correlation analysis showed positive correlations between IH and ISA ( r=0.75, P<0.001), IFH and IFW ( r=0.60, P<0.001), TSD and IFH ( r=0.53, P<0.001), and TSD and IFW ( r=0.40, P<0.001). There was a negative correlation between TSD and IH ( r=-0.46, P<0.001), TSD and ISA ( r=-0.42, P<0.001), IFW and ISA ( r=-0.41, P<0.001), IFW and IH ( r=-0.50, P<0.001), IFH and IH ( r=-0.42, P<0.001). According to Spearman correlation analysis, hierarchical cluster analysis and receiver operating characteristic curve, lumbosacral angle was divided into three types: Type 1, L5 transverse process overlapped with sacral alar; Type 2, 07 mm. Based on lumbosacral triangle classification, different endoscopic techniques were used at L5S1 in 822 patients, including interlaminar approach single-axis endoscopy, trans-foraminal approach single-axis endoscopy, trans-foraminal fenestration approach mobile microendoscopy and unilateral biportal endoscopy, the VAS and ODI of all the patients decreased than those preoperative in immediate postoperative period, half a year postoperative period and the final follow up, and the difference was statistically significant ( P<0.05). At the last follow-up, the Macnab score was excellent in 278 cases, good in 475 cases, and fair in 69 cases, with an excellent and good rate of 91.6% (753/822). Conclusion:Lumbosacral triangle classification is simple and practical, and can effectively guide L5S1 endoscopic surgery.

Objective:To compare the differences in distribution and prognosis of cervical cancer patients in the 2009 and 2018 editions of International Federation of Gynecology and Obstetrics (FIGO) staging, and to analyze the prognostic factors of cervical cancer patients.Methods:The clinical data of 524 cervical cancer patients admitted to the First Affiliated Hospital of Soochow University from January 2010 to December 2018 were retrospectively analyzed. The cases were staged according to the 2009 and 2018 FIGO staging, and the Kendall τb coefficient was calculated to compare the consistency of the distribution of the two stages. Kaplan-Meier was used for survival analysis, and log-rank test was used to test the difference of prognosis in each stage. Cox-regression was used to analyze the prognostic factors of cervical cancer patients.Results:In the 2009 FIGO edition of staging, 1 case of stage ⅠB1 was reduced to stage ⅠA1 due to the microscopic infiltration depth <5 mm, 51 cases of stage ⅠB1 were raised to stage ⅠB2 due to 2 cm4 cm. A total of 119 cases raised to stage ⅢC1 due to pelvic lymph node metastasis, and 11 cases raised to stage ⅢC2 due to para-aortic lymph node metastasis. The distribution of cases in the two stages was consistent (τb=0.61, P<0.001). There were statistically significant differences in overall survival (OS) ( χ2=107.13, P<0.001; χ2=93.02, P<0.001; χ2=92.74, P<0.001) and progression-free survival (PFS) ( χ2=91.95, P<0.001; χ2=77.69, P<0.001; χ2=73.27, P<0.001) among patients with different stages of FIGO in 2018 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, ⅢC1, ⅢC2, Ⅳ) and 2009 (ⅠA, ⅠB, Ⅱ, ⅢA, ⅢB, Ⅳ) and patients with different T stages (T 1, T 2, T 3, T 4). There were statistically significant differences in OS ( χ2=20.71, P<0.001) and PFS ( χ2=24.25, P<0.001) in 2018 FIGOⅠB and ⅢC stages, and there was a statistically significant difference in OS between stage ⅢC1 and stage ⅠB2 ( χ2=6.18, P=0.013). Multivariate analysis showed that age ( HR=1.88, 95% CI: 1.08-3.28, P=0.026), pathological type ( HR=2.11, 95% CI: 1.04-4.27, P=0.038), lymph node metastasis ( HR=2.18, 95% CI: 1.34-3.56, P=0.002), parametrial spread ( HR=2.56, 95% CI: 1.52-4.29, P<0.001), maximum tumor diameter ( HR=1.98, 95% CI: 1.18-3.30, P=0.009), squamous cell carcinoma antigen (SCCA) positive after treatment ( HR=4.49, 95% CI: 2.09-9.68, P<0.001) and Hemoglobin (HB) level before treatment ( HR=0.58, 95% CI: 0.35-0.96, P=0.035) were independent risk factors for OS in patients with cervical cancer. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅠB1, ⅠB2, ⅠB3 were 100%, 97.1% and 87.9% respectively, with a statistically significant difference ( χ2=7.79, P=0.020), and there was a statistically significant difference between stage ⅠB1 and ⅠB3 ( χ2=5.55, P=0.019). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅠB1 and ⅠB2 were 95.7% and 84.3% respectively, with a statistically significant difference ( χ2=9.08, P=0.003). For patients with 2018 FIGO stage ⅠB, SCCA positive after treatment ( HR=1 172.50, 95% CI: 10.37-132 554.51, P=0.003) was an independent risk factor for OS, and differentiation degree ( HR=0.09, 95% CI: 0.01-0.81, P=0.032), treatment method ( HR=0.17, 95% CI: 0.04-0.71, P=0.015) and SCCA positive after treatment ( HR=190.68, 95% CI: 14.27-2 547.67, P<0.001) were independent risk factors for PFS. For patients with 2018 FIGO stage ⅠB, stage ( HR=9.56, 95% CI: 2.38-38.32, P=0.001), SCCA positive after treatment ( HR=126.32, 95% CI: 12.36-1 290.60, P<0.001) and lymph node metastasis ( HR=20.07, 95% CI: 3.63-111.11, P=0.001) were independent risk factors for OS, and differentiation degree ( HR=0.11, 95% CI: 0.02-0.63, P=0.013), treatment method ( HR=0.22, 95% CI: 0.06-0.75, P=0.015) and SCCA positive after treatment ( HR=43.83, 95% CI: 7.94-241.84, P<0.001) were independent risk factors for PFS. According to the 2018 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 95.7% and 75.6% respectively, with a statistically significant difference ( χ2=13.96, P<0.001). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 83.1% and 67.1% respectively, with a statistically significant difference ( χ2=7.61, P=0.006). According to the 2009 FIGO stage, the 5-year OS rates of patients with stage ⅡA and ⅡB were 90.9% and 75.0% respectively, with a statistically significant difference ( χ2=8.85, P=0.003). The 5-year PFS rates of patients with stage ⅡA and ⅡB were 75.7% and 66.7% respectively, with a statistically significant difference ( χ2=4.07, P=0.044). For patients with 2018 FIGO stage Ⅱ, pathological type ( HR=20.28, 95% CI: 2.93-140.32, P=0.002) and stage ( HR=4.35, 95% CI: 1.02-18.55, P=0.047) were independent risks factors for OS. For patients with 2009 FIGO stage Ⅱ, pathological type ( HR=5.82, 95% CI: 1.62-20.94, P=0.007) was an independent risk factor for OS, and pathological type ( HR=3.09, 95% CI: 1.22-7.85, P=0.017) and lymph node metastasis ( HR=2.07, 95% CI: 1.22-3.51, P=0.007) were independent risk factors for PFS. For patients with 2018 FIGO stage Ⅲ, maximum tumor diameter ( HR=3.31, 95% CI: 1.45-7.56, P=0.005) and SCCA positive after treatment ( HR=4.67, 95% CI: 1.22-17.86, P=0.024) were independent risk factors for OS, and pathological type ( HR=4.15, 95% CI: 1.47-11.77, P=0.007) and SCCA positive after treatment ( HR=3.96, 95% CI: 1.45-10.86, P=0.007) were independent risk factors for PFS. Conclusion:The 2018 and 2009 FIGO staging have a good distribution consistency in the cervical cancer patients, and the 2018 FIGO stage ⅠB has more advantages in judging the prognosis, but stage ⅢC cannot accurately judge the prognosis. Lymph node metastasis and maximum tumor diameter are more important prognostic factors.

Metastasis-associated drug resistance accounts for high mortality in ovarian cancer and remains to be a major barrier for effective treatment. In this study, SKOV3/T4, a metastatic subpopulation of ovarian cancer SKOV3 cells, was enriched to explore potential interventions against metastatic-associated drug resistance. Quantitative genomic and functional analyses were performed and found that slug was significantly increased in the SKOV3/T4 subpopulation and contributed to the high resistance of SKOV3/T4. Further studies showed that slug activated c-Met in a ligand-independent manner due to elevated levels of fibronectin and provoked integrin V function, which was confirmed by the significant correlation of slug and p-Met levels in 121 ovarian cancer patient samples. Intriguingly, c-Met inhibitor(s) exhibited greatly enhanced anti-cancer effects in slug-positive ovarian cancer models both and . Additionally, IHC analyses revealed that slug levels were highly correlated with reduced survival of ovarian cancer patients. Taken together, this study not only uncovers the critical roles of slug in drug resistance in ovarian cancer but also highlights a promising therapeutic strategy by targeting the noncanonical activation of c-Met in slug-positive ovarian cancer patients with poor prognosis.

Dihydropyridine (DHP) calcium channel blockers drugs (dipine in drug names) are currently used in the treatment of hypertension clinically. In recent years, with the emergence of generic drugs, it has been found that the drug efficacy is quite different from that of the original drug, and the reason is closely related to the difference in the crystal forms of the oral preparations. This paper reviews the polymorphic phenomenon of some DHP calcium channel blockers in the domestic market, introduces the clinical application and research progress of the DHP drugs, analyzes the differences between different crystal forms of the same drugs. This work may provide references and ideas for the research and development of generic drugs or new crystalline drug of DHP drugs.

Objective: To explore the safety and feasibility of associating diaphragm resection and liver-diaphragmatic metastasis lesions resection for patients with advanced ovarian cancer. Methods: Retrospectively analysis 83 cases(98 times) of advanced ovarian cancer with liver-diaphragmatic metastasis between January 2012 and December 2016 at Department of Liver Surgery, Peking Union Medical College Hospital.The patients were aged from 19 to 75 years.Surgical procedure included metastatic lesions resection(43 times) and stripping(55 times). Operation status, post-operative complications, pathology results and follow-up of the patients were analyzed. Results: Fifteen patients received twice surgical treatment and 68 patients received one time surgical treatment. Postoperative hemorrhage in chest and between liver and diaphragm was not occurred in all cases.Dyspnea and low oxygen saturation were occurred in two cases of stripping patients and 1 case of metastatic lesions resection patients.Results of CT examination indicated that there was medium to large amount of ascites in right chests.The symptoms were relieved after placing thoracic closed drainage.Other patients were recovered smoothly.All patients were diagnosed as ovarian cancer by pathological examination. Conclusion Associating diaphragm resection is safe and feasible for liver-diaphragmatic metastasis lesions from ovarian cancer.

Aim To investigate the effect of bufalin on proliferation and expression of WT1 in K562 cells. Methods The colony number of K562 cell was detec-ted with semi-solid culture assay. The cell cycle was measured by flowcytometry, and the expression of WT1 was observed with immunocytochemistry. Subcutaneous tumor models established by K562 cells in BALB/C nu/nu mice were divided into three groups, including model group, bufalin group and positive control group. After 21 days, the subcutaneous tumors were removed for calculating the inhibitory rate of tumor growth. HE staining and immunohistochemistry were used to ob-serve the morphological changes and the expression of WT1 . Results ① Bufalin could significantly decrease the colony number of K562 cell, arrest it at G0/G1 phase and down-regulate its expression of WT1 in a dose-dependent manner. ② Compared with the model group, the tumor inhibitory rate was much higher, while the volume and the weight were obviously lower in the other two groups. ③Bufalin could induce apop-tosis, necrosis, hemorrhage and fibrosis with HE stai-ning, and down-regulate the expression of WT1. Con-clusion Bufalin could inhibit the proliferation, arrest the cell cycle at G0/G1 phase and down-regulate the expression of WT1 in vitro. Bufalin could inhibit the tumor inhibitory rate, the volume and the weight of the subcutaneous tumors, induce apoptosis, necrosis, hemorrhage and fibrosis with HE staining and down-regulate the expression of WT1 .

Objectives To analyze the deployment of medical equipment and its impacts on medical services of hospitals.Methods Existing data collection,a survey of public hospitals and a chart review of acute myocardial infarction(AMI)inpatients were used to collect related data.Gini coefficients,Chi-square and multivariate model were used to analyze deployment of medical equipment and its impacts on medical services.Results The number of CTs and that of CTs per million population in Pudong new area were higher than those of MRIs and DSAs,and the distribution of CTs among districts in Shanghai was relatively equal(Gini coefficient was 0.20).But lack of DSAs in some public general hospitals had affected the AMI inpatient care.Conclusions Public hospitals and governments in China should keep at a balance the demand of medical services,deployment level of medical equipment,and financial affordability for the society,governments and hospitals.

Aim To evaluate the vasorelaxant effect of two new chemical entities, J35242 and J35243, on iso-lated rat thoracic aorta rings as Rho-kinase inhibitors, and further to explore the underlying mechanisms of these two compounds. Methods Isolated rat thoracic aorta rings pre-contracted by KCl or norepinephrine ( NE) were used to evaluate the vasodilatory effect of J35242 and J35243 . Through the interventions of sev-eral tool drugs, the mechanisms of compounds concern-ing endothelium, K+ channels and Ca2+ were studied. Results J35242 and J35243 showed potent relaxant effect on both KCl and NE pre-contracted vessels, and exhibited partial endothelium dependency. L-NAME and Methylene Blue( MB) could influence the relaxant effect of these compounds. Meanwhile, the compounds could inhibit intracellular Ca2+ release and extracellu-lar Ca2+ influx, which indicated that the compounds might block the calcium channels to relax the vessels. In addition, the two compounds probably did not dilate the aorta rings through opening potassium channels. Conclusions J35242 and J35243 have vasorelaxant effects on vessels in vitro and the potency of J35242 is stronger than that of J35243 . The underlying mecha-nisms might be endothelium-dependent. Also the com-pounds might block Ca2+ channels, lowering intracel-lular Ca2+ concentration to relax the vessels.

Aim To investigate the in vitro vasorelax-ant effect of DL0805-0, a Rho kinase inhibitor, on iso-lated rat thoracic aorta and explore its underlying mechanism. Methods Tension was measured to eval-uate the vasorelaxant effect of DL0805-0 on rat endo-thelium-intact and endothelium-denuded thoracic aorta rings. Rho kinase inhibitor fasudil, nitric oxide syn-thase inhibitor Nω-nitro-L-arginine methyl ester ( L-NAME), guanylate cyclase inhibitor methylene blue, cyclooxygenase inhibitor indomethacin, calcium-activa-ted potassium channel blocker tetraethyl ammonium ( TEA ) , ATP-sensitive potassium channel blocker glibenclamide and voltage-dependent potassium chan-nel blocker 4-aminopyridine ( 4-AP ) were used to il-lustrate the mechanisms of vasorelaxant effect of DL0805-0 . Results DL0805-0 exerted vasorelaxation in a dose-dependent manner in KCl (60 mmol·L-1 ) or NE ( 0. 1 μmol · L-1 ) -induced contraction. DL0805-0-induced vasorelaxation was significantly re-duced by L-NAME. However, methylene blue and in-domethacin did not significantly affect vasorelaxation of DL0805-0. In endothelium-denuded rings, TEA re-markably attenuated the vasorelaxant effect of DL0805-0 , while glibenclamide and 4-AP did not affect vasore laxation of DL0805-0 significantly. DL0805-0 also re-duced NE-induced transient contraction and inhibited contraction induced by increasing extracellular calci-um. Conclusion These results suggest that DL0805-0 induces vasorelaxation through an endothelium-depend-ent pathway. The opening of calcium-activated K+channels and blocking of Ca2+ channels in vascular smooth muscle cells may be one of the mechanisms of DL0805-0-induced vasorelaxation.