ObjectiveTo verify the association between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis by constructing an in vitro co-culture system of testis. MethodsTesticular tissue blocks from 20-25-day-old male rats were placed in an in vitro culture system， and the culture medium was replaced every 2 to 3 days. PCR was used to verify the expression of marker genes of various spermatogenic cells. RNA interference technology was employed to verify the correlation between the Ddit3-Trib3-Akt signaling pathway and rat spermatogenesis. ResultsThe co-culture system could be continuously cultured for more than 2.5 months in vitro. RT-PCR showed that specific marker genes of spermatogonia， spermatocyte and spermoblast were expressed. The RNA and protein expression of Trib3 and Akt changed after the knocking down of Ddit3 and Trib3， respectively. It demonstrated the existence of Ddit3-Trib3-Akt signaling pathway in rat spermatogenesis. ConclusionThe culture time of more than 2.5 months indicates that the culture system can temporarily maintain the proliferation and differentiation of stem cells， and simultaneously maintain and stabilize spermatogenesis in a simple system. The successful validation of the Ddit3-Trib3-Akt signaling pathway also confirms that this culture system can be used to study possible molecular mechanisms of spermatogenesis in vitro.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cancer remains a leading cause of global mortality, necessitating the development of advanced therapeutic strategies with enhanced efficacy and reduced systemic toxicity. Among promising bioactive agents, lactoferrin (LF)—a multifunctional iron-binding glycoprotein abundantly found in mammalian milk and exocrine secretions—has garnered significant interest for its potent and multifaceted anti-cancer properties. This review provides a comprehensive analysis of the current understanding of LF’s role in oncology, encompassing its structural biology, diverse mechanisms of action, and groundbreaking advancements in its application through nano-engineering. LF exerts anti-tumor effects through multiple pathways, including extracellular action, intracellular action, and immune regulation. It demonstrates a remarkable affinity for cancer cell membranes, binding to overexpressed anionic components such as glycosaminoglycans and sialic acids, as well as to specific receptors including the low-density lipoprotein receptor-related protein-1 (LRP-1). This selective binding facilitates targeted uptake. Upon internalization, LF orchestrates a direct assault by inducing cell-cycle arrest in phases such as G0/G1 or S phase through the modulation of key regulators including cyclins, CDKs, and p53. Furthermore, it promotes programmed cell death via apoptotic pathways, involving caspase activation and downregulation of anti-apoptotic proteins such as survivin. A more recently elucidated mechanism is the induction of ferroptosis, an iron-dependent form of cell death characterized by overwhelming lipid peroxidation. Beyond direct cytotoxicity, LF acts as a potent immunomodulator. It enhances natural killer (NK) cell activity, modulates T-lymphocyte populations, and crucially reprograms tumor-associated macrophages (TAMs) from a pro-tumor M2 state to an anti-tumor M1 state, thereby reversing the immunosuppressive tumor microenvironment (TME). The translation of LF’s potential has been significantly accelerated by nanotechnology. The inherent biocompatibility and natural tumor-targeting capabilities of LF make it an ideal platform for sophisticated drug-delivery systems. This review details various fabrication strategies for LF-based nanoparticles (NPs), including self-assembly, sol-in-oil emulsion, and electrostatic nanocomplexes, among others. Research demonstrates that nano-formulations not only protect LF from degradation but also enhance its bioactivity and anti-cancer potency. More importantly, LF NPs serve as versatile carriers for a wide array of therapeutic agents, including conventional chemotherapeutics, natural compounds, and imaging agents. These engineered systems enable synergistic therapy and facilitate site-specific delivery. Notably, the ability of LF to bind to receptors on the blood-brain barrier (BBB) has been leveraged to develop nano-systems for glioblastoma treatment. Other innovative designs utilize LF to modulate the TME—for instance, by alleviating tumor hypoxia to sensitize cells to radiotherapy and chemotherapy. Despite compelling pre-clinical evidence, the clinical translation of LF and its nano-formulations remains nascent. While early-phase trials have established a favorable safety profile for recombinant human LF, larger Phase III studies have yielded mixed results, underscoring the complexity of its action in humans. Key challenges include enhancing drug targeting, optimizing loading efficiency, ensuring batch-to-batch reproducibility, and achieving deep tumor penetration. Future research must focus on the rational design of next-generation LF-NPs. This entails developing standardized manufacturing protocols, engineering “smart” stimuli-responsive systems for targeted drug release in the TME, and constructing multi-targeting platforms. A concerted interdisciplinary effort is paramount to bridge the gap between bench and bedside. In conclusion, LF, particularly in its nano-engineered forms, represents a highly promising and versatile agent in the oncological arsenal, holding immense potential for precise and effective cancer therapy.

Cowden syndrome is a rare autosomal dominant disorder caused by a variant of the PTEN gene,with clinical manifestations mainly of fetal overgrowth and organ tumors.The pregnant woman in this case was 32 years old with gravida 1 and para 0.Prenatal ultrasound in Obstetrics and Gynecology Hospital,Fudan University demonstrated fetal biological parameters abnormally increased(especially in biparietal diameter and circumference of the head)and hepatic tumor.Genetic testing suggested a PTEN gene variant[NM_000314.4:c.193T>G(p.Tyr65Asp)].After termination of pregnancy,autopsy pathology diagnosed fetal organs overgrowth and hepatic hemangioma.This article focuses on the prenatal ultrasound phenotype and genetic features of Cowden syndrome to increase clinicians'awareness of this rare disease.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

Objective To investigate the impacts of epidural anesthesia with ropivacaine combined with dezocine on lower limb motor nerve block and maternal and infant outcomes in primipara undergoing painless delivery.Methods A total of 159 primiparas who delivered in Nanjing Jiangbei Hospital were selected as the research objects,and divided into the blank group(53 cases),the ropivacaine group(53 cases)and the combined group(53 cases)by the random number table method.Parturients in the blank group were given natural delivery mode,parturients in the ropivacaine group were given ropivacaine epidural anesthesia,and parturients in the combined group were given dezocine anesthesia on the basis of ropivacaine.Analgesic effect at different time points,time of the first,second and third stage of labor,pressing times of analgesic pump,lower limbs motor nerve block,maternal and infant outcomes,and adverse reactions of parturients were compared among the three groups.Results At 10 minutes after analgesia,60 minutes after analgesia,when the cervix was fully dilated and when the fetus was delivered,the VAS scores of the parturients in the ropivacaine group and the combined group were lower than those in the blank group(P<0.05),and the VAS scores of the parturients in the combined group were significantly lower than those in the ropivacaine group(P<0.05).There was no significant difference in the time of the first,second or third stage of labor of parturients among the three groups(P>0.05);The pressing times of analgesic pump of parturients in the combined group was significantly less than that in the ropivacaine group(P<0.05).There was no statistically significant difference in terms of low limb motor nerve block after painless labor of parturients among the three groups(P>0.05).There were no statistically significant differences in the perineal incision rate or the Apgar scores of newborns at 1 minute and 5 minutes after birth among the three groups(P>0.05).The usage rate of forceps and the rate of conversion to cesarean section in the combined group were significantly lower than those in the ropivacaine group and the blank group(P<0.05).There was no statistically significant difference in the incidence of total adverse reactions among the blank group,the ropivacaine group and the combined group(P>0.05).Conclusion The combination of ropivacaine and dezocine for epidural anesthesia has a better analgesic effect on primiparas with painless delivery,has a smaller impact on lower limb motor nerve block in parturients,and can achieve better maternal and infant outcomes.

Objective:To investigate the effects of Jianpi Rougan Xifeng Decoction on the behaviors and the Ca 2+ -CaM-CaMK Ⅱ signaling pathway in the striatum of rats with tic disorder models. Methods:Seventy-two SPF-grade SD male rats were randomly divided into blank group, model group, tiapride group (15.93 mg/kg, intragastric administration), low-dose (4.32 g/kg, intragastric administration), medium-dose (8.64 g/kg, intragastric administration) and high-dose (17.28 g/kg, intragastric administration) Jianpi Rougan Xifeng Decoction groups, with 12 rats in each group. Rats in the blank group and model group were gavaged with 0.5 mg/kg of distilled water while rats in other 4 groups were gavaged with corresponding drugs, all rats were gavaged once a day for 28 days.The evaluations of motor behavior and stereotyped behavior were conducted using the Kadasah scoring method and the Diamond scoring method. Calcium content in the striatum was detected using a calcium assay kit. Immunohistochemical analysis was employed to detect the expression of dopamine transporter (DAT) and inositol 1, 4, 5-triphosphate (IP3) in the striatum of rats. Western blot was used to assess the expression of calmodulin (CaM) and calcium/calmodulin-dependent protein kinase Ⅱ (CaMK Ⅱ) in the striatum. RT-PCR was utilized to detect the expression of CaM and CaMK Ⅱ mRNA in the striatum. All data were processed using SPSS 26.0 software, and comparisons among multiple groups were performed using one-way ANOVA and Kruskal-Wallis test.Results:(1) After four weeks of pharmacological intervention, statistically significant differences were observed in the locomotor activity scores and stereotyped scores among the six groups of rats ( H=41.20, 44.24, both P<0.01). Specifically, the locomotor activity scores(3.00(3.00, 3.25), 1.00(0.75, 1.25), 1.00(0.75, 2.00), 1.00(0, 1.00)) and stereotyped scores(3.00(3.00, 4.00), 1.00(0.75, 2.00), 2.00(0.75, 2.00), 1.00(0, 1.25)) in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups were significantly lower than those in the model group (all P<0.01). (2) Results from the calcium assay kit revealed statistically significant differences in striatal calcium content among the six groups of rats ( F=146.67, P<0.01). The calcium content in the tiapride group and the medium- and high-dose Jianpi Rougan Xifeng Decoction groups was significantly lower than that in the model group (all P<0.01). Additionally, the calcium content in the medium-dose ((0.40±0.02)mmol/g) and high-dose ((0.30±0.03)mmol/g) Jianpi Rougan Xifeng Decoction groups was lower than that in the low-dose group ((0.48±0.02)mmol/g) (both P<0.01). (3) Immunohistochemical results showed that there were statistically significant differences in the mean optical density values of DAT and IP3 in the striatum among the six groups of rats ( F=25.57, 154.98, both P<0.01). The IP3 mean optical density in the tiapride group and the Jianpi Rougan Xifeng Decoction groups with medium and high doses exhibited lower values compared to the model group (all P<0.05), whereas the DAT mean optical density displayed higher values in these groups compared to the model group (all P<0.05). The low-dose Jianpi Rougan Xifeng Decoction group also exhibited a lower optical density value of IP3 compared to the model group( P<0.05). The optical density values of IP3 (2.68±0.21, 2.40±0.22) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than that in the low-dose group (4.27±0.23) (both P<0.01). (4) Western blot results indicated that there were statistically significant differences in the protein expression levels of CaM and CaMK Ⅱ in the striatum among the six groups of rats ( F=233.03, 118.60, both P<0.01). The protein expression levels of CaM and CaMK Ⅱ in the tiapride group and the low-dose, medium-dose, and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the model group (all P<0.01). The protein expression levels of CaM (1.02±0.06, 0.84±0.02) and CaMK Ⅱ (0.48±0.03, 0.40±0.02) in the medium-dose and high-dose Jianpi Rougan Xifeng Decoction groups were lower than those in the low-dose group (1.21±0.03, 0.57±0.02)) (all P<0.05). Additionally, the protein expression level of CaM in the high-dose Jianpi Rougan Xifeng Decoction group was lower than that in the medium-dose group( P<0.05).(5) The RT-PCR results indicated significant variations in the mRNA expression levels of CaM and CaMK Ⅱ within the striatum across the six groups rats ( F=30.54, 20.78, both P<0.01). The mRNA expression levels of CaM and CaMK Ⅱ in the tiapride group and the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the model group (both P<0.05). The mRNA expression levels of CaMK Ⅱ (1.38±0.17) in the high-dose Jianpi Rougan Xifeng Decoction group were lower than those in the low-dose group (1.99±0.27) ( P<0.01). Conclusion:Jianpi Rougan Xifeng Decoction can improve locomotor activity and stereotyped behavior in rats with tic disorder model. The mechanism may be through inhibiting the Ca 2+ -CaM-CaMK Ⅱ signaling pathway and regulating the expression of DAT and IP3, thereby modulating the release and recovery of dopamine and reducing the occurrence of tic symptoms.

Cowden syndrome is a rare autosomal dominant disorder caused by a variant of the PTEN gene,with clinical manifestations mainly of fetal overgrowth and organ tumors.The pregnant woman in this case was 32 years old with gravida 1 and para 0.Prenatal ultrasound in Obstetrics and Gynecology Hospital,Fudan University demonstrated fetal biological parameters abnormally increased(especially in biparietal diameter and circumference of the head)and hepatic tumor.Genetic testing suggested a PTEN gene variant[NM_000314.4:c.193T>G(p.Tyr65Asp)].After termination of pregnancy,autopsy pathology diagnosed fetal organs overgrowth and hepatic hemangioma.This article focuses on the prenatal ultrasound phenotype and genetic features of Cowden syndrome to increase clinicians'awareness of this rare disease.

Objective:To observe the efficacy and safety of polatuzumab vedotin(pola)combined with chemotherapy in the treatment of relapsed and refractory diffuse large B-cell lymphoma(R/R DLBCL).Methods:A total of 23 patients with R/R DLBCL treated at the First Affiliated Hospital of Zhejiang University and its Liangzhu Branch from April 2023 to March 2024 were retrospectively collected.All patients were treated with pola combined with chemotherapy regimens such as BR,R-GDP,R-CHOP,or other regimens.Results:All 23 patients were evaluable for efficacy,with 10 achieving complete response(CR),7 partial response(PR),3 stable disease(SD),and 3 progressive disease(PD).The most common adverse events included myelosuppression,fever,and pulmonary infection.No severe adverse events resulted in drug withdrawal.Conclusion:Pola combined with chemotherapy demonstrates promising efficacy and a favorable safety profile in the treatment of R/R DLBCL.

The feasibility for the development of road-rail medical vehicles was discussed.The gap between China's ground medical evacuation system and medical evacuation requirements was analyzed,and the limitations of the existing mobile medical units in China were introduced.The key points for developing road-rail medical vehicles were discussed.The road-rail medical vehicle would be an ideal tool for casualty treatment and rapid evacuation at war time and peace time,which could be a future development direction of the road-rail vehicle and medical train.[Chinese Medical Equipment Journal,2025,46(10):84-90]