Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.

ObjectiveTo explore the medical experience of caregivers of adolescent depression. MethodsIn-depth interviews were conducted with 35 caregivers of hospitalized adolescents with depression undergoing treatment， to explore their experiences and feelings during their children’s medical treatment. The Colaizzi phenomenological seven-step analysis method was employed to summarize and extract themes. ResultsA total of five themes were extracted， including the transformation of attitude towards the disease from denial to acceptance； the treatment process failing to meet expectations； complex emotional experiences featuring the coexistence of hope and disappointment； negative feedback regarding communication with medical staff； difficulties in accessing medical services， and the expectation for more assistance. ConclusionCaregivers lack sufficient knowledge about the disease during their children’s medical-seeking process， the disease treatment process fails to meet expectations， and there is negative feedback regarding communication with medical staff. Overall， medical experience is complex， and current medical services still have deficiencies. It is urgent to pay attention to the medical experiences of caregivers， enhance their disease cognition， standardize the diagnosis and treatment process， improve the effect of doctor-patient communication， expand multi-channel medical-seeking methods， and further meet the needs of patients and caregivers.

Peritoneal metastasis is a common form of distant metastasis in patients with colorectal cancer, and it is typically associated with a poor prognosis. The development of peritoneal metastasis involves complex molecular mechanisms and multifactorial regulation of the tumor microenvironment. Due to the presence of the blood-peritoneal barrier, only a small amount of systemic medication reaches the peritoneal cavity, resulting in limited efficacy against peritoneal metastasis. Intraperitoneal administration shows significant therapeutic advantages as it can directly target the tumor microenvironment, maintain high local drug concentrations, and reduce systemic toxicity. Intraperitoneal chemotherapy, especially hyperthermic intraperitoneal chemotherapy, has become a cornerstone therapeutic strategy in the clinical treatment of peritoneal metastasis. When selecting chemotherapy drugs and drug combinations, pharmacokinetic properties, efficacy, and safety must be comprehensively considered to optimize the treatment outcomes. In addition, the unique microenvironment of the peritoneal cavity provides new treatment approaches for biological treatment strategies, including antitoxins, vaccines, immune checkpoint inhibitors, etc. Techniques such as pressurized intraperitoneal aerosol chemotherapy and novel drug delivery systems demonstrate potential for enhanced efficacy, offering promising alternatives to improve patient outcomes. This article will review peritoneal barrier characteristics, intraperitoneal drug transport, intraperitoneal chemotherapy, and intraperitoneal biological therapies, thereby establishing a theoretical framework for precision therapy in colorectal cancer peritoneal metastasis.

Objective:To observe the effects of Zhulian stimulant type Ⅰ acupuncture on the expression of brain-derived neurotrophic factor (BDNF) and its receptor TrkB and tissue homogenate cyclic adenosine phosphate (cAMP) in rats with diabetic bladder (DCP); To explore the mechanism of Zhulian stimulant type Ⅰacupuncture on DCP.Methods:Totally 50 SD rats were divided into control group, model group, Western medicine group, ordinary acupuncture group, Zhulian stimulant type Ⅰ acupuncture treatment group (acupuncture treatment group) according to random number table method, with 10 rats in each group. DCP rat model was prepared by intraperitoneal injection of streptozotocin (STZ), except for the control group. The Western medicine group was given mecobalamine for gavage; acupoints of "Zhongji", "Sanyinjiao", "Liechou" and "Taichong" were selected. The ordinary acupuncture group was treated with ordinary acupuncture technique, and the acupuncture treatment group was treated with Zhulian stimulant type Ⅰ acupuncture, 1 time/d, 30 minutes/time. Samples were taken after 4 weeks of treatment. The maximum bladder volume, residual urine volume and wet weight of the bladder were detected. The morphology of rat bladder was observed by HE staining. The expression level of BDNF was detected by immunohistochemistry. The expression of cAMP was detected by Western blot. The level of TrkB was determined by ELISA. Real-time fluorescence quantitative PCR (RT-PCR) was used to detect the mRNA expressions of BDNF and cAMP.Results:Compared with model group, maximum bladder volume, residual urine volume and wet weight of bladder in Western medicine group, ordinary acupuncture group and acupuncture treatment group decreased ( P<0.01), and those in Western medicine group and acupuncture treatment group were lower than those in ordinary acupuncture group ( P<0.01). The expressions of BDNF mRNA and protein, cAMP mRNA and protein in Western medicine group, ordinary acupuncture group and acupuncture treatment group increased ( P<0.05), and the level of TrkB increased, and the Western medicine group and acupuncture treatment group were higher than that in ordinary acupuncture group ( P<0.05). Conclusions:Zhuliping stimulant type Ⅰ acupuncture has a protective effect on the bladder function of diabetic rats. The mechanism may be related to the up-regulation of BDNF and mRNA, TrkB, cAMP and mRNA expressions.

Objective:To investigate the clinical effect of endoscopic injection of norepinephrine on cerebral infarction complicated by stress-induced gastrointestinal bleeding.Methods:A total of 150 patients with cerebral infarction complicated by stress-induced gastrointestinal bleeding who were admitted to the Intensive Care Unit of Lishui City People's Hospital from October 2020 to October 2021 were included in this study. These patients were randomly divided into a control group and an observation group using the random number table method, with 75 patients in each group. Patients in the control group received routine clinical treatment, while those in the observation group received endoscopic injection of norepinephrine in addition to routine clinical treatment. The hemostatic time, blood transfusion volume, and length of hospital stay were compared between the two groups. The stress index and inflammatory index were compared between the two groups before and after treatment. The hemostatic effect and adverse reactions were evaluated in each group.Results:The hemostatic time, blood transfusion volume, and length of hospital stay in the observation group were (16.16 ± 4.36) hours, (385.35 ± 41.28) mL, and (5.35 ± 1.28) days, respectively, which were significantly shorter or less than (27.27 ± 6.34) hours, (447.07 ± 32.07) mL, and (7.07 ± 2.07) days in the control group ( t = 12.50, 10.22, 6.12, all P < 0.001). After treatment, the levels of cortisol, norepinephrine, antidiuretic hormone, high-sensitivity C-reactive protein, interleukin-6, and tumor necrosis factor-α in the observation group were (288.33 ± 19.53) mmol/L, (29.17 ± 4.26) μg/L, (4.08 ± 1.08) mU/L, (38.27 ± 8.72) ng/L, (6.69 ± 1.35) μg/L, and (6.37 ± 1.51) mg/L, respectively, which were significantly lower than (327.22 ± 22.01) mmol/L, (39.32 ± 5.54) μg/L, (5.36 ± 1.22) mU/L, (51.24 ± 13.23) ng/L, (8.67 ± 2.29) μg/L, and (11.44 ± 3.13) mg/L in the control group ( t = 11.44, 12.57, 6.80, 7.08, 6.45, 12.63, all P < 0.001). The overall response rate of hemostasis in the observation group was 94.67% (71/75), which was significantly higher than 82.67% (62/75) in the control group ( χ2 = 5.37, P < 0.05). The incidence of adverse reactions in the observation group was 8.00% (6/75), which was slightly, but not significantly, lower than 14.67% (11/75) in the control group ( χ2 = 1.66, P > 0.05). Conclusion:Endoscopic injection of norepinephrine for the treatment of cerebral infarction complicated by stress-induced gastrointestinal bleeding can rapidly stop bleeding, effectively reduce inflammation,improve stress index, and be highly safe.

Chimeric antigen receptor T-cell (CAR-T) therapy has been widely used in patients with hematologic malignancies. However, there are still problems like high relapse rate and limited persistence. Challenges remain in enhancing the efficacy of CAR-T therapy while minimizing the adverse reactions. In recent years, small-molecule compounds, such as Bruton tyrosine kinase inhibitors, tyrosine kinase inhibitors and demethylating drugs, have been shown to have potential synergistic interactions when combined with CAR-T therapy. This review summarizes the latest progress of small-molecular compounds combined with CAR-T therapy in treatment of B lymphocyte malignancies.

OBJECTIVE To evaluate the mechanisms underlying the antidepressant effect of ZBH2012001,a novel serotonin and norepinephrine reuptake inhibitor(SNRI),in general and its ability to enhance monoaminergic transmission and suppress neuroinflammation in particular.METHODS① Male ICR mice were divided into vehicle(distilled water),duloxetine(DLX,10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following ig administration,the antidepressant effect of ZBH2012001 was evaluated using the tail suspension test(TST)and forced swimming test(FST).② Radioligand binding assay was conducted to evaluate the affinity of ZBH2012001 for human serotonin transporters(hSERTs)and human norepinephrine transporters(hNETs).③ Mice were divided into vehicle(distilled water),DLX(10 or 20 mg·kg-1)and ZBH2012001(5,10 and 20 mg·kg-1)groups.One hour following drug administration,the 5-hydroxytryptophan(5-HTP)-induced head-twitch test or yohimbine-induced lethality test were performed to evaluate the effect of ZBH2012001 on the function of the 5-hydroxytryptamine(5-HT)and norepinephrine(NE)systems.④ Mice were divided into vehicle(distilled water+0.1%acetic acid),reserpine model(distilled water+reserpine 5 mg·kg-1),DLX(DLX 20 mg·kg-1+reserpine 5 mg·kg-1)and ZBH2012001(ZBH2012001 5,10 and 20 mg·kg-1+reserpine 5 mg·kg-1)groups.One hour following drug administration,reserpine was injected intraperitoneally to establish a monoamine-depletion model.The ptosis,akinesia,and hypothermia assays were performed to evaluate the effect of ZBH2012001 on the down-regulation of the reserpine-induced monoamine system.The TST in mice was used to evaluate the effect of ZBH2012001 on reserpine-induced depressive-like behavior while high-performance liquid chromatography with electrochemical detection(HPLC-ECD)was used to measure the levels of monoamines and their metabolites in the hippocampal tissue of reserpine-induced monoamine-depletion mice.ELISA was employed to detect the contents of tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.Western blotting was used to assess the expressions of ionized calcium-binding adapter molecule-1(Iba-1)and nuclear factor-kappa B(NF-κB)in the hippocampal tissue of reserpine-induced monoamine-depletion mice.RESULTS ① Compared with the vehicle group,ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the immobility time both in the TST in mice(P<0.01,respectively),and ZBH2012001(20 mg·kg-1)and in the FST in mice(P<0.05).② ZBH2012001 competitively inhibited the binding of[3H]-imipramine to hSERTs and[3H]-nisoxetine to hNETs,with the half maximal inhibitory concentration(IC50)values of 84.95 and 712.90 nmol·L-1,respectively.③Com-pared with the vehicle group,ZBH2012001(10 and 20 mg·kg-1)significantly increased the head twitches induced by 5-HTP in mice(P<0.01,respectively)and increased the mortality rate in mice induced by yohimbine(P<0.05,P<0.01).④ In the reserpine-induced monoamine-depletion model in mice,compared with the vehicle group,mice in the reserpine model group exhibited ptosis,akinesia and hypothermia feature(P<0.01,respectively),significantly prolonged immobility time in the TST(P<0.01),significantly decreased the levels of NE,5-HT and dopamine(DA)(P<0.05,P<0.01),significantly increased the metabolic conversion rate of 5-HT and DA(P<0.01,respectively),significantly elevated levels of TNF-α and IL-6(P<0.05,respectively),and significantly increased expressions of Iba-1 and NF-κB(P<0.05,respectively)in the hippocampus.Compared with the model group,ZBH2012001(5,10 and 20 mg·kg-1)significantly antagonized ptosis and hypothermia behaviors induced by reserpine(P<0.01,respectively),ZBH2012001(10 and 20 mg·kg-1)significantly shortened the immobility time in reserpine-treated mice(P<0.05,P<0.01),ZBH2012001(20 mg·kg-1)significantly increased the levels of NE and 5-HT in the hippocampus of reserpine-treated mice(P<0.05,respectively),decreased the metabolic conversion rate of 5-HT(P<0.05),significantly reduced the contents of TNF-α and IL-6 in the hippocampus of reserpine-treated mice(P<0.05,respectively),ZBH2012001(5,10 and 20 mg·kg-1)significantly reduced the expression of Iba-1 protein in the hippocampus of reserpine-treated mice(P<0.01,respec-tively),and ZBH2012001(20 mg·kg-1)significantly reduced the expression of NF-κB protein in the hippocampus of reserpine-treated mice(P<0.05).CONCLUSION ZBH2012001 exerts its antidepres-sant effect through a dual mechanism involving monoamine enhancement and inflammation suppres-sion.

Objective:To observe the inhibiting effects of manual acupuncture(MA)on bladder cell apoptosis in rats with diabetic neurogenic bladder(DNB)based on the protein and mRNA expression of B-cell lymphoma-leukemia(Bcl)-2,Bcl-2-associated X(Bax)protein,caspase-3,and the protein expression of α-smooth muscle actin(α-SMA),transforming growth factor(TGF)-β in the bladder tissue. Methods:A DNB rat model was established via intraperitoneal injection of streptozotocin(STZ).The rats were randomly divided into a control group,a model group,and an MA group,with 10 rats in each group.For the MA group,MA was applied after modeling.The body mass,fasting blood glucose(FBG),bladder wet weight,and bladder histomorphology were observed.Protein and mRNA expression levels of Bcl-2,Bax,and caspase-3 and the protein expression of α-SMA and TGF-β in the bladder tissue were determined.The apoptotic index of bladder cells was also evaluated. Results:After STZ injection,compared with the control group,the model group and the MA group both showed higher FBG from week 3 and lower body mass from week 9(P<0.05),and had a larger bladder wet weight(P<0.05).Compared with the model group,the MA group showed a smaller bladder wet weight(P<0.05).The histopathological evaluation indicated that MA improved muscle fiber alignment and detrusor cell compensatory hypertrophy in the bladder tissue.In addition,compared with the control group,the apoptotic index increased significantly in the model group and the MA group(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue in the model group and the MA group increased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue decreased significantly(P<0.05).Compared with the model group,the apoptotic index of the MA group decreased significantly(P<0.05);the protein and mRNA expression levels of Bax and caspase-3 and the protein expression level of TGF-β in the bladder tissue decreased significantly(P<0.05),while the protein and mRNA expression levels of Bcl-2 and the protein expression level of α-SMA in the bladder tissue increased significantly(P<0.05). Conclusion:MA can protect the bladder by inhibiting the excessive apoptosis of bladder cells,which may be related to the down-regulation of Bax and caspase-3 proteins and mRNAs and TGF-β protein expression,and the up-regulation of Bcl-2 protein and mRNA and α-SMA protein expression.

Objective:To evaluate the long-term efficacy of endoscopic transluminal drainage(ETD) for acute pancreatitis complicated with walled-off necrosis (WON) or pancreatic pseudocyst (PPC).Methods:A total of 79 patients who were diagnosed as having WON or PPC by abdominal CT or ultrasound and treated with ETD in Nanjing Drum Tower Hospital were enrolled. Past medical records and follow-up by phone call after discharge were analyzed for long-term outcomes including endocrine and exocrine functions and long-term quality of life.Results:A total of 50 patients were enrolled, including 31 patients with infected WON/PPC and 19 patients with uninfected WON/PPC. Seventeen patients (54.84%) in the infected WON/PPC group and 11 patients (57.89%) in the uninfected WON/PPC group lost 5% or more of their weight. There were no significant differences in the proportion of cases of weight loss of 5% or more ( P=0.833), or the weight loss between the two groups (12.59±8.89 kg VS 10.91±2.47 kg, P=0.522). Only one patient in the infected WON/PPC group had chronic abdominal pain. There was no significant difference in the Izbicki score between the two groups (23.79±6.74 VS 22.03±3.21, P=0.295). None of the patients developed steatorrhea after discharge. Five patients (16.67%, 5/30) in the infected WON/PPC group and 6 patients (40.00%, 6/15) in the uninfected WON/PPC group developed endocrine insufficiency with no significant difference ( P=0.140). Greater risk of secondary diabetes resulted from higher low-density lipoprotein cholesterol ( HR=1.9, 95% CI: 1.0-3.4, P=0.044)and triglycerides ( HR=1.2, 95% CI: 1.0-1.3, P =0.029). Conclusion:ETD is safe and effective for WON and PPC. But there is possibility that patients develop secondary diabetes. Additionally, greater risk of secondary diabetes results from higher low-density lipoprotein cholesterol and triglycerides.

Objective:To investigate the correlation between different clinical features and live birth in patients with severe late-onset ovarian hyperstimulation syndrome (OHSS) after in vitro fertilization-embryo transfer (IVF-ET).Methods:The clinical information of 330 patients who were pregnant after IVF-ET and referred to medical treatments diagnosed as late-onset severe OHSS in Peking University Third Hospital from January 2016 to December 2020 was retrospectively analyzed. The patients were divided into live birth achieved group ( n=287) and non-live birth achieved group ( n=43) according to pregnancy outcomes, and live birth achieved group was further divided into two subgroups, full-term birth group ( n=222) and early-term birth group ( n=65) according to gestational week at delivery for better analysis. Single factor and multi-factor analysis were utilized to clarify the influencing factors of both live birth and early-term birth. Results:Among all the patients who received IVF-ET, the incidence of severe OHSS was 0.67% (673/100 758). Among 330 severe late-onset OHSS patients, 42.4% (140/330) had pleural effusion, the incidence of abnormal liver function was 69.4% (229/330), and the live birth rate was 87.0% (287/330). Among the 287 patients who achieved live birth, 55.4% (159/287) had no pleural effusion, 18.5% (53/287) had a small amount of pleural effusion, and 26.1% (75/287) had medium or massive pleural effusion; in the non-live birth achieved group, there were more patients without pleural effusion and less patients with a small amount of pleural effusion; the difference was statistically significant ( χ2=6.213, P=0.045). The rate of selective fetal reduction in live birth achieved group was 16.0% (46/287), which was significantly higher than that in the non-live birth achieved group, which was 2.3% (1/43; χ2=5.749, P=0.017). Multivariate logistic regression analysis revealed that moderately abnormal liver function was an independent risk factor for live birth ( OR=3.15, 95% CI: 1.60-6.19), while selective fetal reduction was an independent protective factor for live birth ( OR=0.13, 95% CI: 0.02-0.96). Additionally, subgroup analysis suggested that twin birth was an independent risk factor for preterm birth ( OR=8.54, 95% CI: 4.31-16.91). Conclusions:Moderate hepatic dysfunction may be associated with adverse pregnancy outcomes in patients with severe late-onset OHSS. Selective fetal reduction and singleton pregnancy are recommended to ameliorate live birth rate, full-term delivery rate, also the maternal and neonatal prognosis for patients with multiple pregnancies.