BackgroundSevere mental disorders represent a major public health concern due to the high disability rates and substantial disease burden， which has garnered significant national attention and prompted their inclusion in public health project management systems. However， credible evidence regarding the current status of disease management and factors influencing disease stabilization among patients with severe mental disorders in Luzhou City， Sichuan Province， remains limited. ObjectiveTo investigate the current management status of patients with severe mental disorders in Luzhou City， Sichuan Province， and to analyze influencing factors of disease stabilization among patients under standardized care， so as to provide evidence-based insights for developing targeted management strategies to optimize clinical interventions for this patient population. MethodsIn March 2023， data were extracted from the Sichuan Mental Health Service Comprehensive Management Platform for patients with severe mental disorders in Luzhou City who received management between December 2017 and December 2022. Information on mental health service utilization and clinical status changes was collected. Trend analysis was conducted to evaluate temporal changes in key management indicators for severe mental disorders in Luzhou City. Logistic regression analysis was employed to identify factors influencing the disease stabilization or fluctuation of these patients. ResultsThis study enrolled a total of 20 232 patients. In Luzhou City， the stabilization rate and standardized management rate of severe mental disorders were 94.89% and 79.36% in 2017， respectively， which increased to 95.33% and 96.92% by 2022. The regular medication adherence rate rose from 34.42% in 2018 to 86.81% in 2022. In 2022， the regular medication adherence rate was 71.80% for schizophrenia， 55.26% for paranoid psychosis， and 51.43% for schizoaffective disorder. Multivariate analysis identified the following protective factors for disease stabilization： age of 18~39 years （OR=0.613， 95% CI： 0.409~0.918）， age of 40~65 years （OR=0.615， 95% CI： 0.407~0.931）， urban residence （OR=0.587， 95% CI： 0.478~0.720）， and regular medication adherence （OR=0.826， 95% CI： 0.702~0.973）. Risk factors for disease fluctuation included poor （OR=1.712， 95% CI： 1.436~2.040）， non-inclusion in care-support programs （OR=1.928， 95% CI： 1.694~2.193）， non-participation in community rehabilitation （OR=2.255， 95% CI： 1.930~2.634）， and intermittent medication adherence （OR=3.893， 95% CI： 2.548~5.946）. ConclusionThe stability rate， standardized management rate， and regular medication adherence rate of patients with severe mental disorders in Luzhou City have shown a year-by-year increase. Age， household registration status， economic condition， medication compliance， and community-based rehabilitation were identified as influencing factors for disease fluctuation in these patients. ［Funded by Luzhou Science and Technology Plan Project （number， 2022-ZRK-186）］

Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

This paper reports a case of neonatal lupus syndrome manifested by metabolic disease. A male neonate was admitted to the Children's Hospital of Soochow University due to poor response and vomiting for 1 day. Based on the clinical symptoms, including the patterned skin and a full anterior fontanelle, and a result of leukocytosis, neonatal sepsis was considered. Lysinuric protein intolerance was not excluded from the genetic metabolic disorders screening. The patient was positive for lupus-related autoantibodies and antinuclear antibodies, which were also found in his mother and elder sister. He had no functional variant of the SCL7A7 gene, a gene related to lysinuric protein intolerance, thereby the diagnosis of neonatal lupus syndrome manifested by metabolic disorders was confirmed. After treatment with methylprednisolone, the patient recovered well with no specific change in blood genetic metabolism at re-examination. Monthly follow-up after discharge found decreased antibody titers.

Objective: Cisplatin resistance is a huge problem encountered in ovarian cancer treatment. Our study probed the roles and the underlying mechanisms of lncRNA MCF2L-AS1 in ovarian cancer cisplatin-resistance. Methods: SKOV3 and IGROV-1 cells were subjected to gradually increasing concentrations of cisplatin to construct ovarian cancer cisplatin-resistance cells. Cell proliferation was evaluated by cell counting kit-8 and colony formation assays. Cell apoptosis was assessed using Annexin V and PI staining. The relationships between SP1, MCF2L-AS1 and insulin-like growth factor-2 mRNA binding protein 1 (IGF2BP1) were verified by RNA pull-down, RIP, ChIP and dual-luciferase reporter gene assay, respectively. Tumor xenograft experiment was employed to evaluate the effects of MCF2L-AS1 silencing on ovarian cancer cisplatin-resistance in vivo. TUNEL staining and immunohistochemistry were performed in tumor tissue. Results: MCF2L-AS1 and IGF2BP1 were upregulated in cisplatin-resistant cells. MCF2L-AS1 silencing suppressed cell proliferation of cisplatin-resistant cells, while promoted the apoptosis, suggesting that MCF2L-AS1 knockdown suppressed ovarian cancer cells cisplatin-resistance. Meanwhile, MCF2L-AS1 silencing enhanced cisplatin sensitivity in ovarian cancer parental cells and IGF2BP1 overexpression impaired cisplatin sensitivity of parental cells. MCF2L-AS1 activated IGF2/MEK/ERK pathway through interacting with IGF2BP1. Transcription factor SP1 activated MCF2L-AS1 expression. MCF2L-AS1 knockdown inhibited ovarian cancer cisplatin-resistance in vivo. Conclusion SP1-induced MCF2L-AS1 promoted ovarian cancer cisplatin-resistance through activation of IGF2/MEK/ERK pathway via interacting with IGF2BP1.

Objective This study was conducted to evaluate treatment-related toxicities,the patterns of failure,overall survival(OS)and progression-free survival(PFS)by comparing IFI with ENI in combination with chemotherapy. Methods Eligible patients were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. The primary end points wereacute treatment-related toxicities. The secondary end points were patterns of failure,OS and PFS. Kaplan?Meier survival rate of the method for calculating the Logrank test difference method. Results Between April 2012 and October 2016,a total of 228 patients were enrolled from nine centers in china. Grade≥3,Grade≥2 radiation esophagitis and pneumonitis in the IFI arm were significantly lower than that of the ENI arm(P=0.018,0.027).No significant differences were observed in overall failure rates,loco-regional failure,distant failure rates,in-field and out-field lymph node failure between the two arms(P=0.401,0.561,0.510,0.561,0.681).The 1-,2-, 3-,4-yearand median OS in the ENI arm and IFI arm were 84.1%,57.3%,39.4%,31.6%,28 months and 83.6%,62.1%,44.5%,31.5%,32 months(P=0.654),respectively. The 1-,2-,3-yearand median PFS in the ENI arm and IFI arm were 71.9%,42.3%,32.7%,20 months and 70.1%,45.0%,35.9%,22 months (P=0.885),respectively. Conclusions Compared to ENI,IFI resulted in decreased radiation pneumonitis and esophagitis without sacrificing loco-regional lymph nodal control,PFS and OS in thoracic ESCC. Clinical Trial Registry Chinese Clinical trail registry,registration number:NCT01551589.

Objective To explore the anti‐cancer effects of physiological deep‐sea water(PDSW) combined with hyperther‐mia for hepatocellular carcinoma in vitro .Methods Deep‐sea water (DSW) from the south Chinese sea was processed ,and made in‐to PDSW ,detection of some elements .In vitro ,the cultured normal liver cells and human hepatoma QGY‐7703 cells were randomly divided into PDSW group and normal saline(NS) group ,the NS group received saline ,the PDSW group received different concentra‐tions of PDSW .Two groups were heated respectively to 6 h of 40 ℃ or 1 h of 43 ℃ ,24 ,48 ,72 h after the administration of PDSW or saline ,the normal liver cells and QGY‐7703 cells proliferation capacity and toxicity were investigated by MTT assay .At the same time testing PDSW and NS in 40 ℃ 6 h for 10 d state of human liver QGY‐7703 cell clone formation rate .Results The results of MTT assay showed that tumor inhibitory rate were time and concentration dependent in tow groups .Tumor inhibitory rate of PD‐SW group in different time was significantly higher than NS group (P<0 .05) .On the other hand ,the inhibitory of hepatocyte for PDSW group in different time were significantly lower than NS group .In addition ,the clone formation rate of PDSW group was lower than those of NS group(P<0 .05) .Conclusion PDSW can improve the heat tolerance of normal liver cells .When combine with heat ,it can obviously inhibit the growth of human liver cancer QGY‐7703 cells .

Objective To explore the effects of physiological deep-sea water(PDSW) on hyperthermal tolerance of Kunming (KM ) mice in the 45 .0 ℃ environment .Methods Deep-sea water from the south Chinese sea was processed ,and the metallic ele-ments dissolved in the DSW were analysed .The mice were randomly divided into 2 groups :the control group received tap water ;the experimental group treated with PDSW for 15 d .And then the mice were fed in the 45 .0 ℃ conditions .The survival time and histo-morphometric analyses of the brain ,lung ,heart ,liver and kidney were investigated .Results The survival time in PDSW-fed group was significantly longer than that of the control group (P< 0 .05) .Moreover ,histomorphometric analyses showed that PDSW could protect the brain ,lung ,heart ,liver and kidney of KM mice from the 45 .0 ℃ conditions .The results of western blot revealed that ex-pression of HSP72 of liver tissues for PDSW-fed group substantially increased ,when compared with the control mice(P< 0 .05) . Conclusion PDSW could improve hyperthermal tolerance of KM mice ,which maybe in the relation with expression of HSP72 pro-moted by PDSW .

Objective To investigate the effect and mechanism of tetrahydrobiopterin ( BH4) on the angiogenesis in hepatocellular carcinoma ( HCC) .Methods BALBc/-nu mice were subcutaneously injected with HepG-2 cells and randomly divided into control and BH 4 groups.The BH4 group and control group received 20 mg/kg BH4 or saline by intraperitoneal injection daily for two weeks , respectively .The level of BH4was measured by high performance liquid chromatography (HPLC), the level of nitric oxide (NO) was measured by Griess test array , the transcriptional level of K-ras was measured by quantitative RT-PCR, and the protein expressions of guanosine triphosphate cyclohydrolase Ⅰ( GTPCH ) , endothelial nitric oxide synthase ( eNOS) , phospho-Akt and Akt were determined by Western blot .Results BH4 level in the tumor tissues of BH4 group was (0.24±0.02) μg/ml, significantly higher than the (0.17±0.01) μg/ml in the control group (P<0.01).The level of NO in the tumor tissues of BH4group was (51.44±2.90) mmol/L, significantly higher than the (24.77±0.54) mmol/L in the control group( P<00.1 ).The tumor volume of BH4 group was (191.05±8.70) mm3, significantly higher than the (103.10±5.03) mm3 in the control group (P<0.01).The expressions of CD34 , K-ras, phospho-eNOS, phospho-Akt and GTPCH were significantly up-regulated in the tumor tissues of BH4 group when compared with those of the control group (P<0.01). Conclusions BH4 recognized as an essential cofactor of eNOS can increase tumor-produced NO by activating the wild-type Ras-PI3K/Akt pathway, thus induces angiogenesis .This might provide a novel and promising way to control the progression of hepatocellular carcinoma through targeting BH 4 synthesis pathway and inhibiting angiogenesis .

Objective To investigate the effect and mechanism of tetrahydrobiopterin ( BH4) on the angiogenesis in hepatocellular carcinoma ( HCC) .Methods BALBc/-nu mice were subcutaneously injected with HepG-2 cells and randomly divided into control and BH 4 groups.The BH4 group and control group received 20 mg/kg BH4 or saline by intraperitoneal injection daily for two weeks , respectively .The level of BH4was measured by high performance liquid chromatography (HPLC), the level of nitric oxide (NO) was measured by Griess test array , the transcriptional level of K-ras was measured by quantitative RT-PCR, and the protein expressions of guanosine triphosphate cyclohydrolase Ⅰ( GTPCH ) , endothelial nitric oxide synthase ( eNOS) , phospho-Akt and Akt were determined by Western blot .Results BH4 level in the tumor tissues of BH4 group was (0.24±0.02) μg/ml, significantly higher than the (0.17±0.01) μg/ml in the control group (P<0.01).The level of NO in the tumor tissues of BH4group was (51.44±2.90) mmol/L, significantly higher than the (24.77±0.54) mmol/L in the control group( P<00.1 ).The tumor volume of BH4 group was (191.05±8.70) mm3, significantly higher than the (103.10±5.03) mm3 in the control group (P<0.01).The expressions of CD34 , K-ras, phospho-eNOS, phospho-Akt and GTPCH were significantly up-regulated in the tumor tissues of BH4 group when compared with those of the control group (P<0.01). Conclusions BH4 recognized as an essential cofactor of eNOS can increase tumor-produced NO by activating the wild-type Ras-PI3K/Akt pathway, thus induces angiogenesis .This might provide a novel and promising way to control the progression of hepatocellular carcinoma through targeting BH 4 synthesis pathway and inhibiting angiogenesis .

Objective This experiment aimed to study the influence of deep sea water (DSW) on wound healing of mice .Methods 24 Mice were randomly divided into two groups :group DSW(n=12) and group sterilize tap water(STW)(n=12) ,freely feeding for 14 days respectively ,and calculated the amount of food and water .On the 15th day ,1 cm × 1 cm size of wound was established on the back area of mice ,and continued to feed with DSW and STW respectively .Tracking the wound healing rate .Specimen was taken in the edge of wound tissue on postoperative 3 ,5 ,7 days ,then observed histopathological changes .Results Compared group DSW with group STW ,there was no significant difference in the total amount of food and water .5 days after the formation of wounds ,the wound healing rate of group DSW was significantly higher than group STW .Histological observation :compared with group STW ,vascular endothelial cells and new capillaries of the group DSW was increased ,and group DSW had less inflammatory cell and more fibroblast cells proliferation .Conclusion deep sea water can promote wound healing .