ObjectiveThis paper aims to systematically reveal the effect difference and mechanisms of Zishenwan against chronic prostatitis （CP） before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex based on an integrated strategy of ultra-high performance liquid chromatography-quadrupole-orbitrap mass spectrometry （UPLC-Q-Orbitrap-MS/MS）， network pharmacology， and serum metabolomics. MethodsZishenwan samples before and after salt-processing of Anemarrhenae rhizoma and Phellodendri chinensis cortex were extracted by alcohol-water dual extraction. The chemical components of each sample were detected by UPLC-Q-Orbitrap-MS/MS， and differential components were screened by multivariate statistical analysis. Network pharmacology analysis was performed based on the identified chemical components of Zishenwan to construct a protein-protein interaction （PPI） network of "component， target， and pathway"， and the core components， targets， and pathways of Zishenwan against CP were screened. Forty-two male Sprague-Dawley （SD） rats were randomly divided into a blank group， a model group， a Qianliekang group （1.54 g·kg^-1）， low- and high-dose raw Zishenwan groups （1.8， 5.4 g·kg^-1）， and low- and high-dose salt-processed Zishenwan groups （1.8， 5.4 g·kg^-1）. The CP rat model was established by intraprostatic injection of carrageenan. After one week of recovery， the rats were administered the corresponding drugs for 21 days， while those in the blank group and model group received the same volume of normal saline. After the experiment， serum and tissue samples were collected to evaluate pharmacodynamic indicators including organ indices， histopathology， and inflammatory factors in serum. Subsequently， untargeted serum metabolomics technology was used to analyze metabolite changes and perform pathway enrichment analysis. The network pharmacology was used to construct a network of "differential metabolite， reaction， enzyme， and gene". ResultsA total of 76 components were identified in raw and salt-processed Zishenwan， and 34 differential components were screened by multivariate statistical analysis. Among them， the contents of 14 components， including berberine， berberrubine， and phellodendrine， increased after salt-processing， while the contents of 20 components， such as neomangiferin， decreased. The 28 active components and 185 potential targets were screened out by network pharmacology. The core components included berberine， phellodendrine， magnoflorine， and jatrorrhizine， and the core targets included signal transducer and activator of transcription 3 （STAT3）， protein kinase B1 （Akt1）， and transcription factor AP-1 （JUN）. These targets were significantly enriched in pro-inflammatory signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） and mitogen-activated protein kinase （MAPK）. Compared with the model group， all Zishenwan administration groups showed decreased prostate index， reduced levels of interleukin （IL）-1β， IL-18， and B-cell lymphoma-2 （Bcl-2） in serum （P<0.05， P<0.01）， as well as varying degrees of alleviation in histopathological damage. At the same dose， compared with the raw Zishenwan groups， the salt-processed Zishenwan groups showed lower prostate index， pathological scores， and IL-1β， IL-18， and Bcl-2 levels in serum， but the differences were not statistically significant. Metabolomics reveals that 38 differential metabolites were reversed after salt-processed Zishenwan administration. Both raw and salt-processed Zishenwan regulated pathways such as β-alanine metabolism and tryptophan metabolism. In addition to the common regulated pathways， the salt-processed group specifically regulated pantothenate and coenzyme A biosynthesis， pyrimidine metabolism， and arginine and proline metabolism. The intersecting pathways between network pharmacology and metabolomics were tryptophan metabolism and arginine and proline metabolism， with overlapping targets including monoamine oxidase A （MAOA） and arginase 1 （ARG1）. ConclusionThe increased contents of components such as berberine and phellodendrine in salt-processed Zishenwan may enhance its therapeutic effect on CP by inhibiting the PI3K/Akt and MAPK signaling pathways， along with multi-target regulation of tryptophan， arginine， and pantothenate metabolism pathways to comprehensively regulate inflammatory and immune responses.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective:To investigate the effectiveness and safety of secondary cytoreductive surgery (SCS) in patients with platinum-sensitive recurrent epithelial ovarian cancer who progressed after first-line maintenance therapy with poly adenosine diphosphate ribose polymerase inhibitor (PARPi).Methods:Clinical pathological data and prognostic information were retrospectively collected from 30 ovarian cancer patients who underwent SCS between January 2018 and June 2024. The Kaplan-Meier method was used to analyze the second progression-free survival (PFS2) time and 3-year overall survival (OS) rate.Results:(1) Primary treatment: the median age at diagnosis was 51.3 years. A total of 40% (12/30) patients underwent primary debulking surgery with an expectation of achieving no gross residual disease (R0), while 60% (18/30) received neoadjuvant chemotherapy and interval debulking surgery. Optimal cytoreduction was achieved in 93% (28/30) of patients. BRCA1/2 gene testing was performed in 29 patients (testing rate 97%, 29/30), identifying 11 BRCA-mutated (37%, 11/30) and 18 BRCA wild-type (60%, 18/30) patients. The median duration of PARPi maintenance therapy among the 30 patients was 11.9 months; patients with BRCA gene mutations had a median duration of 19.2 months, while those with BRCA wild-type had a median duration of 10.1 months. (2) Secondary surgery: pathologically confirmed recurrence patterns, single lesion in 9 patients (30%, 9/30), oligo-lesion (2 lesions) in 3 patients (10%, 3/30), and multi-lesion (≥3 lesions) in 18 patients (60%, 18/30). Among the 30 patients, optimal cytoreduction was achieved in 97% (29/30) of SCS patients, with suboptimal cytoreduction in 1 patient (3%, 1/30). Adjuvant chemotherapy included platinum+paclitaxel in 24 (80%, 24/30) patients and platinum+liposomal doxorubicin in 6 (20%, 6/30) patients. PARPi re-treatment was administered to 17 patients (57%, 17/30) after chemotherapy. (3) Efficacy and safety: as of the follow-up cutoff in June 2024, the median follow-up time was 28.0 months. A total of 19 (63%, 19/30) patients experienced the next recurrence. The median PFS2 time after SCS was 18.5 months. Recurrence occurred in 7 BRCA-mutated and 12 BRCA gene wild-type patients. Median PFS2 time was significantly longer in BRCA-mutated patients compared to BRCA wild-type patients (25.7 vs 14.1 months; P=0.028). Three deaths occurred during follow-up, resulting in a 3-year OS rate of 90%. Among the 30 patients, postoperative complications occurred in 4 patients (13%, 4/30). One patient developed a ureteral fistula on 7 days post-SCS requiring ureteral stenting, and one patient was transferred to the intensive care unit on 1 day post-SCS due to hypovolemic shock. No deaths occurred within 30 days after SCS. Conclusion:For platinum-sensitive recurrent ovarian cancer patients progressed after first-line PARPi maintenance therapy who are anticipated to achieve R0 resection, SCS represents a safe and effective second-line treatment option.

Objective:To compare the pregnancy and neonatal outcomes of in vitro fertilization-embryo transfer(IVF-ET)with fresh or frozen embryos in spouses of patients with severely low sperm concentration and motility.Methods:A total of 2300 patients whose spouses have severely low sperm concentration and motility underwent IVT-ET in the Reproduction Medicine Center,Sir Run Run Shaw Hospital from April 2018 to April 2022.After applying the propensity score matching(PSM),473 fresh embryo transferred cycles and 473 frozen embryo transferred cycles were selected for the study,and the pregnancy and neonatal outcomes were compared between the two groups.Results:There were no significant differences in pregnancy outcomes and neonatal outcomes between fresh and frozen embryo groups(all P＞0.05).In the stratification analysis,the number of retrieved oocytes in the fresh good-quality embryo transfer group was significantly increased compared with the fresh poor-quality embryo group(P＜0.05),but the very early pregnancy loss rates were similar between the two groups(P＞0.05),while the rate in fresh good-quality embryo transfer group was significantly higher than that in the frozen good-quality embryo transfer group(P＜0.05).Among different age groups of women,the number of retrieved oocytes and the level of estrogen in the fresh embryo transfer group was significantly higher in the 20 to＜30 years old group than that in the 30 to＜35 years old group(both P＜0.05),but the clinical pregnancy rate was lower in the 20 to＜30 years old group than that in the 30 to＜35 years old group(P＞0.05).Additionally,the very early pregnancy loss was significantly increased in the fresh embryo group compared with the frozen embryo group in the 20 to＜30 years age group(P＜0.05).Conclusions:There were no significant differences in pregnancy and neonatal outcomes between fresh and frozen embryo transfer in spouses of patients with severely low sperm concentration and motility undergoing IVF-ET.Due to the shorter transfer times,less embryo freezing damage and reduced costs,fresh embryo transfer can be considered as the first choice.However,it is not necessary to pursue fresh embryo transfer if maternal oestrogen levels are too high and there is a tendency of overstimulation.

Objective To explore the role of MAPK4 in cervical squamous cell carcinoma(CSCC)for the identification of candidate prognostic prediction biomarkers and molecular therapeutic targets.Methods The TCGA cohort was subjected to Kaplan-Meier survival analysis.Immunohistochemistry experiments were conducted on clinical samples to explore the correlation between MAPK4 and patient prognosis.A nomogram was constructed based on MAPK4 mRNA levels.Western blot,CCK-8,colony formation,and Transwell cell function experiments were performed to clarify the abnormal expression and role of MAPK4 in CSCC.DIA proteome sequencing was used to identify effector molecules regulated by MAPK4.Combined with the above cell function experiments,the knockdown of MAPK4 and the overexpression of effector molecules revealed that MAPK4 regulated effector molecules to mediate tumor progression.Results CSCC patients with elevated MAPK4 mRNA levels and high protein expression have a worse prognosis.The constructed nomogram based on MAPK4 can accurately predict the 1-,3-,and 5-year survival rates of patients.Compared with that in normal cervical tissues,MAPK4 protein expre-ssion was up-regulated in tumors.MAP-K4 knockdown substantially inhibited the proliferation,colony formation,mig-ration,and invasion of CSCC ME180 and SiHa cells.SLC3A2 is a downs-tream effector molecule of MAPK4.Overexpression SLC3A2 can weaken the inhibitory effect of MAPK4 knockdown on cell proliferation,colony formation,migration,and invasion.Conclusion MAPK4 is a candidate prognostic biomarker for patients with CSCC.MAPK4 positively regulates SLC3A2 protein expression and accelerates tumor progression,making it a potential molecular therapeutic target for patients with CSCC.

Objective:To investigate the factors for serious complications within 30 days after surgery in elderly patients with advanced epithelial ovarian cancer(EOC)who undertook primary debulking surgery(PDS).Methods:The clinical data of International Federation of Gynecology and Obstetrics(FIGO)stage ⅢC/Ⅳ EOC patients aged≥60 years who received PDS in gynecological department of National Cancer Center and National Center of Gerontology between January 2014 and December 2018 were retrospectively analyzed.Clavien-Dindo scoring system was applied to grade the complications within 30 days after surgery.The serious early postoperative complications were those of grade Ⅲ or above occurred within 30 days after surgery.Multivariate Logistic regression analysis was used to screen the independent risk factors of serious complications within 30 days after surgery.Results:A total of 133 patients were included in this study and serious complications rated 11.3%(15/133). The mean age of patients in severe complication group was significantly higher than that in the control group[(69.80±6.56) vs.(65.87±5.14), t=2.699, P=0.008]. The proportion of patients with preoperative ECOG score≥2 was significantly higher in the severe complication group than that in the control group[26.7%(4/15) vs.5.9%(7/118), χ2=4.985, P=0.026], and the proportion of preoperative hypoalbuminemia(<35 g/L)was significantly higher in the severe complication group[20.0%(3/15) vs.3.4%(4/118), χ2=4.897, P=0.027]. However, there was no significant difference in intraoperative bleeding, R0 resection rate as well as surgical complexity( χ2=1.964, 0.330, 4.637, all P>0.05)between the two groups.Multivariate Logistic regression analysis showed that the independent factors for serious early postoperative complications were age≥70 years( OR=4.345, P=0.028), ECOG score≥2( OR=25.619, P=0.008)and preoperative albumin <35 g/L( OR=6.733, P=0.040). Conclusions:In the elderly ovarian cancer patients, individualized perioperative management should be strengthened for the patients with factors associated with serious early postoperative complications, in order to reduce severe complications and improve the prognosis.

In recent years, antiangiogenic drugs based on VEGF and VEGFRs signaling pathway have been widely used in the treatment of malignant tumors. Apatinib is an orally bioavailable small-molecule antiangiogenic agent and can specifically inhibit the tyrosine kinase activity of VEGFR, thereby inhibiting tumor angiogenesis. Apatinib is the first-level recommendation of third-line treatment of gastric cancer in CSCO Guidelines for the Diagnosis and Treatment of Gastric Cancer published in 2018. Apatinib has been proved to be effective and safe in gastric, lung and breast cancers. In addition, the drug shows great potential in the treatment of a variety of solid tumors. This article reviews the recent progress on the mechanism, clinical efficacy, related efficacy predictors of apatinib and its combination with other antitumor drugs.

Objective To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stageⅠb2, Ⅱa2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results Of 177 patients, 133 (75.1%) had stageⅠb2 and 44 (24.9%) hadⅡa2 cancers. After NACT,overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions The effect of NACT in Ⅰb2, Ⅱa2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size>3 cm after NACT adversely affect 5-year OS rate.

Objective: To explore the effects and postoperative prognostic factors in cervical cancer patients received neoadjuvant chemotherapy combined with surgery and post-operative adjuvant therapy. Methods: A total of 177 patients with cervical cancer at International Federation of Gynecology and Obstetrics (FIGO) stage Ⅰ b2, Ⅱ a2 who underwent neoadjuvant chemotherapy (NACT) followed by surgery with and without adjuvant therapy in Cancer Hospital, Chinese Academy of Medical Sciences were included. Univariate and multivariate analyses of 5-year overall survival (OS) rate and 5-year disease-free survival (DFS) rate were performed. Results: Of 177 patients, 133 (75.1%) had stage Ⅰb2 and 44 (24.9%) had Ⅱa2 cancers. After NACT, overall response rate was 63.3% (112/177) including 12 cases of complete response (CR), 100 of partial response (PR) and no progressive disease (PD) case. At a median follow-up of 59.2 months, the 5-year DFS rate was 73.6% and the 5-year OS rate was 86.8%. Univariate analysis revealed that lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year DFS rate (P<0.05). Lymph node metastasis, deep stromal invasion and tumor size after NACT significantly affected 5-year OS rate (P<0.05). The multivariate analysis showed that, stromal invasion (outer 1/3 or outer 1/2) was independent risk factor of 5-year DFS rate (P<0.05), and 5-year OS rate was significantly affected by tumor size >3 cm after NACT (P<0.05). Conclusions The effect of NACT in Ⅰ b2, Ⅱ a2 squamous carcinoma of the uterined cervix is confirmed. The independent risk factor for 5-year DFS rate in patients received NACT and hysterectomy is deep stromal invasion of the cervix. The presence of tumor size >3 cm after NACT adversely affect 5-year OS rate.

Objective? To develop a health care needs assessment tool for the elderly at home, which is in line with China's national conditions. Methods? Guided by Zuluaga-Raysmith model theory, a health care needs assessment tool for the elderly was developed through literature review, theoretical analysis, expert review, expert consultation and pre-survey. Results? An item pool of 10 first-level items and 72 second-level items, which were suitable for home-based elderly health care needs assessment tools was initially formed. Through three rounds of national expert consultation and pre-survey, an elderly health care needs assessment tool consisting of 7 first-level items, 10 second-level items and 61 third-level items was formed. The expert authority coefficient was 0.791, the expert positive coefficient was 100%, and the expert coordination coefficient was 0.935 (P＜ 0.05). Conclusions The pool of items for the assessment tool is reasonably formed, the results of Delphi expert consultation are reliable. The scale can be widely used after adjustment. It can help medical staff quickly and comprehensively understand the current situation of health care needs of the elderly, provide support for the accurate construction of long-term care service system for the elderly, and support the development of community/home care for the elderly.