OBJECTIVE To investigate the mechanism of pachymic acid on renal injury in pregnancy induced hypertension （PIH） rats by regulating the silent information regulator transcript 1/peroxisome proliferator-activated receptor γ coactivator-1α （Sirt1/PGC-1α） pathway. METHODS Pregnant SD rats were prepared by co-caging and PIH model was induced using N-nitro-L- arginine methyl ester （L-NAME） method. PIH rats were randomly divided into model group， L-pachymic acid （low-dose pachymic acid， 10 mg/kg） group， H-pachymic acid （high-dose pachymic acid， 20 mg/kg） group， and H-pachymic acid+EX527 （20 mg/kg pachymic acid+10 mg/kg EX527） group， with 6 rats in each group. Another 6 normal pregnant rats were selected as blank group. Each group was given relevant medicine or solvent intragastrically or intraperitoneally daily， once a day， for 28 consecutive days. After the last administration， 24 h urinary protein and tail artery systolic blood pressure （SBP） were measured in pregnant rats from each group， along with the levels of serum creatinine （Scr）， blood urea nitrogen （BUN），uric acid （UA）， and cystatin C （Cys-C）. The contents of superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， and 8-hydroxy-2′-deoxyguanosine （8-OHdG） in renal tissue， as well as the mRNA and protein expression levels of Sirt1 and PGC-1α， were also determined. Meanwhile， renal histopathological changes in rats from each group were evaluated using hematoxylin-eosin （HE） staining and periodic acid-Schiff （PAS） staining. RESULTS Compared with model group， L-pachymic acid group and H-pachymic acid group exhibited significant decreases in 24 h urine protein quantification， tail artery SBP， Scr， BUN， UA， Cys-C levels， glomerulosclerosis index score of renal tissue， renal tubular injury score， the percentage of PAS positive area， MDA and 8-OHdG （P＜0.05）. Conversely， the contents of SOD and GSH-Px， along with the mRNA and protein expression levels of Sirt1 and PGC-1α， were significantly increased （P＜0.05）. Moreover， these improvements were more pronounced in H-pachymic acid group （P＜0.05）. Compared with H-pachymic acid group， the aforementioned indicators in pregnant rats from the H-pachymic acid+EX527 group showed significant reversal （P＜0.05）. CONCLUSIONS Pachymic acid significantly ameliorates renal injury induced by PIH in rats， potentially through activation of the Sirt1/PGC-1α pathway.

ObjectiveTo investigate the influencing factors and independent risk factors for lower extremity deep vein thrombosis （DVT） in patients with acute necrotizing pancreatitis （ANP）， to analyze the effectiveness of three commonly used risk assessment models for thrombosis （Caprini score， Padua score， and Wells score）， and to provide a reference for clinical identification of high-risk individuals and optimization of prevention and treatment strategies. MethodsA retrospective analysis was performed for the clinical data of 320 patients with ANP who were admitted to Luzhou People’s Hospital and The Affiliated Hospital of Southwest Medical University from April 2013 to April 2024， and according to the presence or absence of DVT during hospitalization， the patients were divided into thrombosis group with 25 patients and control group with 295 patients. After propensity score matching， the two groups were compared in terms of past history and various examination results during hospitalization. The risk factors for lower extremity DVT in ANP patients during hospitalization were analyzed through univariate and multivariate Logistic regression， and a DVT risk prediction model was established based on independent influencing factors. The receiver operating characteristic （ROC） curve was used to assess the performance of models， and the DeLong test was used for comparison of the area under the ROC curve （AUC）， sensitivity， and specificity. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups； the chi-square test was used for comparison of categorical data between groups. ResultsAfter matching， the patients were divided into thrombosis group with 24 patients and control group with 112 patients. The clinical characteristics analysis showed that compared with the control group， the thrombosis group had significantly higher degree of pancreatic necrosis， D-dimer level， Bedside Index for Severity in Acute Pancreatitis （BISAP） score， and proportion of patients undergoing dialysis （all P<0.05）. The multivariable Logistic regression analysis showed that BISAP score， degree of pancreatic necrosis， and D-dimer level were independent risk factors for lower extremity DVT in ANP patients during hospitalization （all P<0.05）. The BISAP-Caprini score model had an AUC of 0.832 （95% confidence interval： 0.722 — 0.942， P<0.001） in predicting the risk of lower extremity DVT， with a Youden index of 1.661， an optimal cut-off value of 0.26， a sensitivity of 75.0%， and a specificity of 91.1%. ConclusionD-dimer， BISAP score， and the degree of pancreatic necrosis are independent risk factors for lower extremity DVT in patients with ANP during hospitalization， and the BISAP-Caprini score model can effectively predict the risk of DVT in ANP patients.

Ferroptosis is a key driver of the onset and progression of chronic obstructive pulmonary disease （COPD）. By exploring the role of ferroptosis in COPD from the perspective of "qi deficiency with retention and stagnation"， it is considered that mitochondrial dysfunction and imbalanced antioxidant defenses are the microscopic manifestations of "qi deficiency"， whereas iron accumulation and lipid peroxide deposition constitute the pathological basis of "retention and stagnation". In traditional Chinese medicine （TCM）， the treatment principle is tonifying deficiency and benefiting qi， scattering retention and unblocking stagnation. Its mechanism involves improving the antioxidant system and mitochondrial function to enhance cellular resistance to ferroptosis， as well as relieving pulmonary iron overload， excessive lipid peroxidation， and inflammatory factor release to reduce the accumulation of pathological products， thereby exerting therapeutic effects on COPD.

China has entered the ranks of “moderately aging” countries. The aging of the population is accompanied by the phenomenon of a low birth rate， with insufficient newborns and an increasing proportion of the elderly population， resulting in aging issues persisting. Conversely， the low birth rate has further exacerbated the degree of aging， promoting China’s fertility policy to focus on constructing an effective fertility support policy system to comprehensively enhance the fertility willingness of the reproductive-age groups. At the current stage， China’s fertility support policy system seeks to reduce the costs of childbearing， alleviate family child-rearing burdens， ease work-family conflicts， and meet childcare needs for reproductive-age individuals， infants， and caregivers through providing economic， time， and service support. However， numerous issues persist throughout the process from design to application and implementation， such as policy fragmentation， unclear responsibilities， and mismatched supply and demand. The current policy objectives tend to emphasize population regulation， lacking systematic support for the entire lifecycle of families. Furthermore， China’s fertility support policies have partially drawn on international experience and undergone localized adjustments， receiving varying degrees of feedback. This validates that research should focus on the heterogeneous effects of fertility support policies on the fertility willingness of different reproductive-age groups and identify their specific fertility needs. This approach would facilitate more precise policy implementation and more effectively construct the entire lifecycle fertility support policy system， thereby achieving high-quality development of the population.

Objective: To assess the impact of long-term antiretroviral therapy (ART) on human immunodeficiency virus (HIV) blood screening outcomes in post-exposure prophylaxis (PEP) failure cases through a longitudinal analysis of blood screening results over a 7-year period in a patient with HIV PEP failure. Methods: This study conducted 13 follow-up assessments for a high-risk individual who initiated ART shortly after exposure. The effectiveness of various blood screening methods, including immunological assays and nucleic acid testing (NAT), was analyzed. Blood samples were also tested with HIV RNA quantification testing, Western blot (WB) confirmation testing, chemiluminescence immunoassay (CLIA), and HIV rapid tests utilizing gold and selenium labels. A comprehensive analysis was performed to evaluate the changes in diagnostic capabilities of different testing methods for HIV biomarkers over an extended period following PEP failure. Results: The patient had two high-risk exposures: one day before ART initiation (BA1) and seven days preceding treatment (BA7). On the first day after the ART treatment (AA1), the HIV RNA concentration (viral load) was 9.07×10 copies/mL; by day five (AA5), the viral load decreased to 1.04×10 copies/mL. At day eleven (AA11), NAT and ELISA tests were both positive, with the WB result remaining indeterminate (gp160+). At day 48 (AA48), the S/CO value of the fourth generation ELISA reagent was 1.07, while results from a 6-sample pool and quantitative NAT were negative. However, a single sample NAT returned a positive result and WB tests indicated positivity for p17, p24, and gp160. At AA74, the quantitative NAT rebounded to 2.83×10 copies/mL, with positive NAT results for single and 6-sample pool NAT tests. The S/CO values of the imported and domestic ELISA reagents were 3.39 and 23.44, respectively. At AA201, 6-sample pool and quantitative NAT were negative again, while single sample NAT remained positive. From AA319 to AA2221, all NAT results have remained consistently below the minimum detection limit. At AA2221, S/CO values of the imported and domestic ELISA reagents were 3.47 and 23.44, respectively. Conclusion: The findings indicate that patients experiencing PEP failure after high-risk HIV exposure are at a higher risk of being missed by mixed-sample NAT pools and individual serological tests. Nonetheless, anti-HIV antibody levels are sustained at elevated values for an extended duration, underscoring antibody testing as an effective measure for blood screening.

Objective: To compare quality control (relative purity and specific activity) and process control [plasminogen (Pg) antigen recovery and potency recovery] indexes of samples before and after adding the Q chromatography step to the full chromatography process of human Pg, thereby determining whether the addition of this step could improve Pg recovery by affinity chromatography. Methods: A Q chromatography step was added before the Pg affinity chromatography in the original Pg chromatography process. The loading solution, flow through solution and eluate of Q chromatography and Pg affinity chromatography were collected. The potency of coagulation factor Ⅱ (FⅡ), Ⅶ (FⅦ), Ⅷ (FⅧ), Ⅸ (FⅨ), and Ⅹ(FⅩ) were detected by the coagulation method, the total protein content was detected by the BCA method, and the Pg potency was detected by the chromogenic substrate method. The content of specific plasma proteins was detected by immunoturbidimetry, the potency recovery of coagulation factors was calculated, and the flow direction of coagulation factors was analyzed. The recovery of different plasma protein antigens were calculated, and the distribution of impurity proteins was analyzed. The relative purity and specific activity of Pg, antigen content, and potency recovery in the target fractions were calculated and compared with the original process indicators, so as to determine the effect of adding Q chromatography on the original process. Furthermore, the reproducibility after process modification was assessed. Results: 100% of FⅡ, FⅩ, and FⅨ, 87.81% of FⅧ, and 40.44% of FⅦ in filtered plasma were removed by Q chromatography. The residual FⅦ (53.26%) and FⅧ (13.30%) in Q flow-through fraction were completely removed by Pg affinity chromatography. In both the original process (without Q-chromatography) and the modified process (with Q-chromatography), non-target plasma proteins mainly existed in the flow-through fraction of Pg affinity chromatography. The antigen recovery of IgM, ceruloplasmin (CER), and fibronectin (FNC) in Q-chromatography flow-through fraction were reduced. In contrast, antigen recovery of other plasma proteins [IgG, IgA, Pg, albumin (AlB), alpha-1-antitrypsin (AAT), and fibrinogen (Fg)] were all >90%, which were consistent with the protein composition and proportion in the original affinity chromatography loading solution. Compared with the recovery rate of Pg antigen in the original process (74.4%), the total recovery of Pg antigen in the modified process was significantly increased (89.97%). Compared with the recovery of IgG (97.48%) and Fg (95.32%) in the Pg affinity flows-through fraction of the original process, the modified process resulted in a slight reduction in the recovery of IgG (94.60%), while the recovery of Fg was not affected (95.05%). The potency recovery rate, specific activity, and relative purity of Pg after Q chromatography were 99.3%, 0.016 U/mg, and 0.15%. These values were the same as those of Pg affinity chromatography loading solution by the original process, indicating that introduction of Q chromatography did not affect subsequent Pg affinity chromatography. Compared with the recovery of Pg antigen in three batches of the original process (66.49±1.02)%, the recovery of Pg antigen in the affinity chromatography eluent of the modified process [five batches; (77.43±4.43)%] was significantly improved. Furthermore, the potency recovery was (86.80±4.28)%, the relative purity was (81.99±1.25)%, the specific activity was (8.679±1.073)U/mg, and the process was reproducible. Conclusion: The addition of Q chromatography could improve the recovery of Pg affinity chromatography in the full chromatography process.

Objective To evaluate the efficacy and safety of botulinum toxin A (BTX-A) injection into the external urethral sphincter in combination with sacral neuromodulation (SNM) for the treatment of idiopathic non-obstructive urinary retention (INOUR). Methods A total of 57 INOUR patients treated in our hospital during May 2022 and May 2024 were enrolled. Patients were divided into the BTX (n=30) and combined groups (n=27) according to whether they chose SNM after BTX-A injection. The baseline, postoperative 1-month and 6-month consecutive 3-day voiding diaries, quality of life score (QoL), and post-void residual (PVR), preoperative and postoperative 1-month urodynamic results, and postoperative complications were recorded and compared between the two groups. Results One month after surgery, the average number of voiding frequency per day and PVR were lower in both groups than those before surgery (P<0.05), while the average daily urine volume and maximum flow rate (MFR) were higher (P<0.05). There was no statistically significant difference between the maximum detrusor pressure during micturition in both groups before and after surgery (P>0.05). One month after surgery, the average number of voiding frequency per day, average daily urine volume, PVR, QoL, MFR, bladder compliance (BC), and maximum cystometric capacity (MCC) were better in the combined group than in the BTX group (P<0.05), and the efficiency was higher in the combined group (88.9% vs.63.3%, P<0.05). Six months after surgery, the efficacy of the BTX group returned to the baseline level with no statistically significant difference, whereas the efficacy of the combined group was stable (not different from the postoperative 1-month indicators, but better than the baseline level). During the follow-up, there was no difference in the incidence of complications between the BTX group and combined group [43.3% (13/30) vs. 48.1% (13/27), P>0.05]. Conclusion BTX-A injection into the external urethral sphincter combined with SNM improves the short-term outcomes of INOUR patients and maintains the efficacy 6 months postoperatively, which is a safe and reliable treatment option.

The unique characteristics of the deep space environment, microgravity, cosmic radiation, and extreme temperature fluctuations, are emerging as major driving forces for pharmaceutical innovation. These factors provide new avenues for optimizing drug formulations, improving crystal structure quality, and accelerating the discovery of therapeutic targets. Advances in deep space research not only help overcome critical bottlenecks in terrestrial drug development but also promote progress in structure-based drug design and deepen understanding of cellular stress-response mechanisms. Current progress in space-based pharmaceutical research primarily includes the study of disease mechanisms under microgravity, protein crystallization in microgravity, and drug development utilizing deep space radiation and resources. However, the operational complexity, high costs, and limited data reproducibility of space experiments remain key challenges hindering widespread application. Looking ahead, with the integration of automation, artificial intelligence analysis, and on-orbit manufacturing, deep space drug development is expected to achieve greater scalability and precision, opening a new frontier in biopharmaceutical science.
Drug Design ; Drug Development/methods* ; Humans ; Weightlessness ; Space Flight ; Artificial Intelligence ; Extraterrestrial Environment

OBJECTIVES: Stress urinary incontinence (SUI) is a common condition among women that severely impairs quality of life. Pelvic floor proprioceptive training (PFPT) has attracted increasing attention for its potential to enhance pelvic floor muscle function and alleviate SUI symptoms. This study aims to observe and compare the clinical efficacy of PFPT combined with electroacupuncture, electrical stimulation, and biofeedback therapy versus conventional therapy consisting of electroacupuncture, electrical stimulation, and biofeedback alone in women with SUI, and to explore the role of PFPT in improving symptom and functional outcomes. METHODS: In this randomized controlled trial, 72 women with mild to moderate SUI were recruited from the Department of Rehabilitation Medicine at Third Xiangya Hospital, Central South University, between December 2021 and October 2023. Participants were randomly assigned to an experimental group (n=36) or a control group (n=36). Both groups received health education. The control group underwent electroacupuncture combined with electrical stimulation and biofeedback therapy, while the experimental group additionally received PFPT 3 times per week for 4 weeks. The primary outcome was assessed using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Secondary outcomes included pelvic floor muscle strength, bladder neck mobility, and balance ability. The ICIQ-SF was reassessed at 1, 3, 6, and 12 months post-treatment. RESULTS: Both groups showed statistically significant improvements in all parameters after treatment (all P<0.05). However, there were no statistically significant differences between groups in most measures (all P>0.05). The experimental group demonstrated longer single-leg stance duration with eyes closed than the control group (left leg: P=0.026; right leg: P=0.006), with a significant increase from baseline (P<0.001). At 6 months post-treatment, the cure rate in the experimental group was significantly higher than that in the control group (P=0.037). CONCLUSIONS Conventional therapy effectively improves SUI symptoms, but adding PFPT provides notable additional benefits, including enhanced balance ability and sustained mid-term cure rates. These findings suggest that PFPT is a valuable adjunct to standard SUI management strategies.
Humans ; Female ; Urinary Incontinence, Stress/physiopathology* ; Pelvic Floor/physiopathology* ; Middle Aged ; Biofeedback, Psychology ; Adult ; Exercise Therapy/methods* ; Proprioception ; Electroacupuncture/methods* ; Quality of Life ; Electric Stimulation Therapy/methods* ; Treatment Outcome ; Combined Modality Therapy