Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Objective:To explore the effectiveness, safety, and cost among urinary follicle-stimulating hormone (u-FSH), recombinant FSH (r-FSH)α, and r-FSHβ in the early follicular phase prolonged protocol for patients under 35 years old with normal ovarian function.Methods:It was a retrospective cohort study. Patients under 35 years old with normal ovarian function who underwent early follicular phase prolonged protocol for ovulation stimulation and using in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization in Reproductive Health Hospital of the Third Affiliated Hospital of Zhengzhou University from January 2018 to December 2023 were recruited, including the fresh and frozen-thawed embryo transfer (FET) cycles. Patients were divided into u-FSH group, r-FSHα group, and r-FSHβ group. A total of 1 048 ovarian stimulation cycles were included, with 150 cycles, 490 cycles and 408 cycles in the three groups respectively. A total of 710 FET cycles with fresh cycle cancellation were included, with 95 cycles, 320 cycles and 295 cycles in the three groups respectively. The baseline data, pregnancy outcomes, safety, and cost were compared among the three groups. The main observation indicators were cumulative pregnancy rate and cumulative live birth rate (CLBR). A binary logistic regression model was used to control confounding factors, and to analyze the relationship between three ovulation inducing medicine and CLBR. Results:The difference in the number of oocytes retrieved among the u-FSH group, r-FSHα group, and r-FSHβ group was statistically significant [13.0 (10.0, 16.0), 14.0 (11.0, 18.0), 15.0 (11.0, 19.0), respectively, P=0.012], and the difference in the number of 2PN embryos was statistically significant [9.0 (6.0, 12.0), 10.0 (7.0, 13.0), 10.0 (7.0, 13.0), respectively, P=0.046]. There were no statistically significant differences in the number of available embryos, available embryo rate, the number of high-quality embryos, high-quality embryo rate, available blastocyst formation rate, fresh cycle clinical pregnancy rate, live birth rate in fresh cycle, cumulative pregnancy rate of frozen embryos with fresh cycle cancellation, CLBR of frozen embryos with fresh cycle cancellation, cumulative clinical pregnancy rate, CLBR, moderate to severe ovarian hyperstimulation syndrome incidence, ectopic pregnancy rate, multiple pregnancy rate and neonatal malformation rate among the three groups (all P>0.05). In terms of economy, the u-FSH group had the lowest total gonadotropin cost for each patient, while the r-FSHα group had the highest. The differences among the three groups were statistically significant [u-FSH group 4 429.08 (3 198.78, 5 044.23) yuan, r-FSHα group 6 023.72 (5 433.75, 7 529.65) yuan, r-FSHβ group 5 480.00 (4 550.90, 6 437.86) yuan, P<0.001]. Binary logistic regression analysis was conducted, using u-FSH as a control. The CLBR of the r-FSHα group and r-FSHβ group showed no statistically significant difference compared with the u-FSH group (a OR=0.95, 95% CI: 0.57-1.58, P=0.838; a OR=0.89, 95% CI: 0.54-1.48, P=0.654). Conclusion:For patients under 35 years old with normal ovarian function undergoing long protocol ovarian stimulation, the effectiveness and safety of the three ovarian-stimulating medicine are similar, but u-FSH has economic advantages.

Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid decline in renal function. Renal ischemia-reperfusion injury (RIRI) is one of the main causes of AKI with the underlying mechanism incompletely clarified. The liver X receptors (LXRs), including LXRα and LXRβ, are members of the nuclear receptor superfamily. It has been shown that LXRs play an important role in regulating glucose and lipid metabolism, cholesterol efflux, and inflammation. The purpose of this study was to explore the role and mechanism of LXRs in RIRI. We determined the effects of LXR activation on renal function and histological changes in a mouse RIRI model and a cellular model of hypoxia/reoxygenation (H/R). In vivo results showed that LXRs agonist GW3965 significantly inhibited the increase of serum creatinine and urea nitrogen levels induced by RIRI. Both HE and PAS staining of kidney tissues revealed that GW3965 alleviated the morphological damages caused by RIRI. Immunohistochemical staining showed that GW3965 mitigated 4-HNE and GRP78 levels induced by RIRI. Furthermore, TUNEL assay indicated that GW3965 reduced RIRI-induced renal cell apoptosis. Quantitative real-time PCR (qPCR) analysis revealed that GW3965 attenuated RIRI-induced IL-6 and IL-1β mRNA expression. Compared with wild-type group, LXRα gene deficiency had little effect on RIRI-associated renal functional decline and morphological damages. Additionally, in vitro study demonstrated that GW3965 alleviated H/R-induced decrease of HK-2 human renal proximal tubule cell viability and restored the activity of superoxide dismutase (SOD) after H/R. Western blot results showed that GW3965 mitigated the increase of 4-HNE and GRP78 protein expression levels after H/R; However, knockdown of LXRβ using the small interfering RNA (siRNA) technique reduced cell viability compared to GW3965-treated group. Taken together, the LXRs agonist GW3965 significantly alleviates RIRI in mice possibly by reducing apoptosis, oxidative stress, endoplasmic reticulum stress and inflammation. These results also preliminarily confirm that the renal protective effects of LXRs agonists are dependent on LXRβ.
Animals ; Liver X Receptors/genetics* ; Reperfusion Injury/prevention & control* ; Mice ; Benzoates/pharmacology* ; Benzylamines/pharmacology* ; Male ; Endoplasmic Reticulum Chaperone BiP ; Mice, Inbred C57BL ; Apoptosis ; Acute Kidney Injury/prevention & control* ; Kidney/pathology* ; Humans

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Pancreatic cancer is a highly malignant tumor with a poor prognosis. It is very hard to treat pancreatic cancers for their high heterogeneity, complex tumor microenvironment, and drug resistance. Currently, gemcitabine plus nab-paclitaxel, capecitabine and FOLFIRINOX are standard chemotherapy for resectable or advanced metastatic pancreatic cancer. Considering the limited efficacy and toxic side effects of chemotherapy, targeted and immune drugs have gradually attracted attention and made some progress. In this article, we systematically reviewed the chemotherapeutic drugs, targets and related targeted drugs, and immunotherapy drugs for pancreatic cancer.

Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.

Objective: To explore the clinical characteristics of various types of infected pancreatic necrosis(IPN) and the prognosis of different treatment methods in the imaging classification of IPN proposed. Methods: The clinical data of 126 patients with IPN admitted to the Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University from December 2018 to December 2021 were analyzed retrospectively. There were 70 males(55.6%) and 56 females(44.4%), with age(M(IQR)) of 44(17)years (range: 12 to 87 years). There were 67 cases(53.2%) of severe acute pancreatitis and 59 cases (46.8%) of moderately severe acute pancreatitis. All cases were based on the diagnostic criteria of IPN. All cases were divided into Type Ⅰ(central IPN)(n=21), Type Ⅱ(peripheral IPN)(n=23), Type Ⅲ(mixed IPN)(n=74) and Type Ⅳ(isolated IPN)(n=8) according to the different sites of infection and necrosis on CT.According to different treatment strategies,they were divided into Step-up group(n=109) and Step-jump group(n=17). The clinical indicators and prognosis of each group were observed and analyzed by ANOVA,t-test,χ² test or Fisher exact test,respectively. Results: There was no significant difference in mortality, complication rate and complication grade in each type of IPN(all P>0.05). Compared with other types of patients, the length of stay (69(40)days vs. 19(19)days) and hospitalization expenses(323 000(419 000)yuan vs. 60 000(78 000)yuan) were significantly increased in Type Ⅳ IPN(Z=-4.041, -3.972; both P<0.01). The incidence of postoperative residual infection of Type Ⅳ IPN was significantly higher than that of other types (χ²=16.350,P<0.01). There was no significant difference in the mortality of patients with different types of IPN between different treatment groups. The length of stay and hospitalization expenses of patients in the Step-up group were significantly less than those in the Step-jump group(19(20)days vs. 33(35)days, Z=-2.052, P=0.040;59 000(80 000)yuan vs. 122 000(109 000)yuan,Z=-2.317,P=0.020). Among the patients in Type Ⅳ IPN, the hospitalization expenses of Step-up group was significantly higher than that of Step-jump group(330 000(578 000)yuan vs. 141 000 yuan,Z=-2.000,P=0.046). The incidence of postoperative residual infection of Step-up group(17.4%(19/109)) was significantly lower than that of Step-jump group(10/17)(χ²=11.980, P=0.001). Conclusions: Type Ⅳ IPN is more serious than the other three types. It causes longer length of stay and more hospitalization expenses. The step-up approach is safe and effective in the treatment of IPN. However, for infected lesions which are deep in place,difficult to reach by conventional drainage methods, or mainly exhibit "dry necrosis", choosing the step-jump approach is a more positive choice.
Male ; Female ; Humans ; Retrospective Studies ; Pancreatitis, Acute Necrotizing/complications* ; Acute Disease ; Intraabdominal Infections/complications* ; Necrosis/complications* ; Treatment Outcome

OBJECTIVE: To explore the effect of Shenmai Injection (SMI) on the long-term prognosis of patients with chronic heart failure (CHF). METHODS: The Hospital Information System was used to extract data of CHF patients, and the retrospective cohort study was conducted for analysis. In non-exposed group, standardized Western medicine treatment and Chinese patent medicine or decoction were applied without combination of SMI while in the exposed group, SMI were applied for more than 7 days. Evaluation indicators are followed with New York Heart Association functional classification (NYHA classification), left ventricular ejection fraction (LVEF), N-terminal brain natriuretic peptide precursor (NT-ProBNP), cardiogenic death and heart failure (HF) readmission. Statistical analysis includes Kaplan-Meier analysis and Cox regression which are used to explore the relationship between SMI and outcome events. RESULTS: A total of 1,211 eligible CHF patients were involved and finally 1,047 patients were followed up successfully. After treatment, the cases of NYHA classification decline in the exposed and non-exposed groups accounted for 64.30% and 43.45%, respectively; the improvement values of LVEF were 8.89% and 7.91%, respectively; the improvement values of NT-ProBNP were 909 pg/mL and 735 pg/mL, respectively. After exposure on SMI, the rates of cardiogenic death and HF readmission reduced from 15.43% to 10.18% and 38.93% to 32.37%. According to Kaplan-Meier analysis, the log-rank P value of SMI and cardiogenic death was 0.014, while the counterpart of SMI and HF readmission was 0.025. Cox regression analysis indicated that for cardiogenic death, age, cardiomyopathy, diabetes, and NYHA classification were risk factors while β-blockers, aldosterone receptor antagonists, Chinese patent medicine/decoction and SMI were protective factors. Likewise, for HF readmission, age, cardiomyopathy, and NYHA classification were risk factors while SMI was a protective factor. CONCLUSION Combination with SMI on the standardized Western medicine treatment can effectively reduce cardiogenic mortality and readmission rate in CHF patients, and thereby improve the long-term prognosis.
Biomarkers ; Drug Combinations ; Drugs, Chinese Herbal ; Follow-Up Studies ; Heart Failure/drug therapy* ; Humans ; Natriuretic Peptide, Brain ; Peptide Fragments ; Prognosis ; Retrospective Studies ; Stroke Volume ; Ventricular Function, Left

Antibodies, Monoclonal, Humanized/adverse effects* ; Humans ; Immune Checkpoint Inhibitors/adverse effects* ; Myocarditis/drug therapy*

OBJECTIVE To prepare curcumin /berberine co -loaded self -microemulsion drug delivery system （CUR/BER- SMEDDS）and evaluate its physicochemical properties and in vitro anti-tumor effects . METHODS Using CUR and BER as model drug，based on the screening of the type of oil phase ，emulsifier，co emulsifier and their mass ratio ，the formulation of CUR/BER - SMEDDS were optimized by central composite design -response surface methodology ，taking particle size and drug loading as evaluation parameters ，with the mass percentage of oil phase and the mass ratio of emulsifier to co emulsifier as factors ，and verification test was conducted . CUR/BER-SMEDDS prepared by optimized formulation were evaluated in terms of physicochemical properties，in vitro dissolution and in vitro anti-tumor effects . RESULTS The optimized formulation of CUR/BER -SMEDDS included that the oil phase was medium chain triglyceride （30.97%），the emulsifier was polyoxyl 40 hydrogenated castor oil （46.77%），the co emulsifier was polyethylene glycol 400（22.26%），and the mass ratio of emulsifier to co emulsifier was 2.10∶1. The validation experiments showed that mean particle size of CUR/BER -SMEDDS was（58.90±5.41）nm，the average drug loading was（94.94±3.87）mg/g，and the relative deviations from the predicted values were －2.90% and －0.14%，respectively. The CUR/ BER-SMEDDS prepared by optimal formulation was light yellow ，clear and transparent liquid after emulsified with water ，and its particles were spherical . The results of dissolution test in vitro showed that after SMEDDS was made ，the cumulative dissolution of CUR in artificial intestinal fluid and artificial gastric fluid and that of BER in artificial intestinal fluid were significantly higher than those of its raw material . Results of in vitro anti-tumor experiment showed that IC 50 values of CUR/BER -SMEDDS for PC -3 cells and DU -145 cells were （17.38±2.84）and（20.89±1.26）μmol/L，which were all lower than those of CUR and EBR significantly （P＜0.05）.CONCLUSIONS The optimized prepar ation process of CUR/BER -SMEDDS is stable and feasible . The drug release of CUR/BER-SMEDDS is more complete than that of single drug，and has stronger anti -prostate cancer effect in vitro .