Objective Objective To analyze the potential spatial factors affecting the genetic differentiation of Oncomelania hupensis robertsoni in Yunnan Province. Methods A total of 13 administrative villages were selected from schistosomiasis-endemic areas of Yunnan Province as O. hupensis snail sampling sites. At least 200 snails were collected in each site, and the spatial variable data of each site were recorded, including longitude, latitude and altitude. Thirty active and Schistosoma japonicum uninfected O. hupensis snails were selected from each sampling site by means of the crawling method and the cercarial shedding method. Genomic DNA was extracted from O. hupensis snails. Following PCR amplification, purification of PCR amplification products and sequencing, the gene sequences of O. hupensis snail samples were spliced and edited using the DNAstar software and the NCBI database to yield the complete mitochondrial sequences of O. hupensis snails at each sampling site, and the mitochondrial genetic distance matrix of O. hupensis robertsoni was calculated at each sampling site. The geographical coordinates of each sampling site were marked using the software ArcGIS 10.2, and the straight-line geographical distance between each sampling site was calculated. The altitude difference, longitude difference and latitude difference between each sampling site were calculated using the Excel software, and the correlation between the mitochondrial genetic distance matrix of O. hupensis robertsoni and each spatial variable matrix was examined by using the Mantel test at 13 sampling sites in Yunnan Province. Results Among the 13 O. hupensis snail sampling sites in Yunnan Province, the largest mitochondrial genetic distance of O. hupensis robertsoni snail populations was seen between Anding Village, Nanjian Yi Autonomous County and Caizhuang Village, Midu County (26.244 2), and the largest geographical distance was seen between Dongyuan Village, Gucheng District and Cangling Village, Chuxiong County (272.64 km). The highest altitude difference was seen between Anding Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1 086.10 m), and the largest longitude difference was found between Qiandian Village, Eryuan County and Cangling Village, Chuxiong County (1.86°), while the largest latitude difference was measured between Leqiu Village, Nanjian Yi Autonomous County and Dongyuan Village, Gucheng District (1.81°). In addition, the mitochondrial genetic distance of O. hupensis robertsoni snail populations was positively correlated with altitude at 13 snail sampling sites in Yunnan Province (r = 0.542 8, P < 0.001), and showed no significant correlations with geographical distance (r = 0.093 4, P > 0.05), longitude (r = −0.199 5, P > 0.05) or latitude (r = 0.205 7, P > 0.05). Conclusion Altitude may be a potential spatial factor affecting the genetic differentiation of O. hupensis robertsoni in Yunnan Province.

Background In 2021, chronic obstructive pulmonary disease (COPD) emerged as the forth leading cause of death in the world. However, the impact of air pollutants on COPD is still inconsistent across current studies. Objective To analyze the relationship between ambient sulfur dioxide (SO₂) exposure and hospital admissions for COPD in Lanzhou, and to examine the modified effects of SO₂ across different genders, age groups, and seasons. Methods A total of 20718 hospital admission records for COPD were collected from Lanzhou between 2016 and 2020, alongside synchronized data on SO₂ concentration and meteorological variables. A generalized additive model integrated with a distributed lag nonlinear model was used to assess the relationship and the lag effects between SO₂ exposure and COPD admissions. Potential confounders, including meteorological factors, day-of-the-week effect, and holidays, were controlled for, with a maximum lag period set at 7 d. Two-pollutant models and sensitivity analyses were conducted to ensure robustness. Results are expressed as relative risks (RR) with 95% confidence intervals (95%CI). Results During the study period, the average daily number of COPD admissions was 11.34±7.03. The average mass concentration of SO₂ was (23.72±12.35) μg·m⁻³. SO₂ exposure was positively correlated with COPD admissions; specifically, each 10 μg·m⁻³ increase in SO₂ concentration was associated with an RR of 1.440 (95%CI: 1.317, 1.573). Stratified analyses found that at a cumulative lag of 7 d, the RRs were higher among females, individuals aged ≥65 years, and during the cold season. Conversely, no significant increase in COPD admission risk related to SO₂ was observed during the warm season. For every 10 μg·m⁻³ increase in SO₂ concentration, the RR was 1.483 (95%CI: 1.311, 1.678) for females, 1.441 (95%CI: 1.311, 1.583) for those aged > 65 years， and 1.595 (95%CI: 1.313, 1.937) during the cold season. Conclusion Short-term exposure to ambient SO₂ exposure in Lanzhou is associated with an increased risk of COPD admission. The association is more pronounced among females, the elderly (aged> 65 years) and during the cold season.

p21 (encoded by the CDKN1A gene) is a critical cell cycle regulatory protein endowed with versatile biological functions. In various sex hormone-related cancers, p21 exhibits a paradoxical dual role, capable of both inhibiting tumorigenesis and promoting cancer progression, exerting dual, often opposing, effects on cellular fate that are dictated by the specific context. The clinical targeting of p21 remains elusive, largely due to its functionally pleiotropic and context-dependent nature within intricate regulatory networks. During the initial, hormone-dependent phase of cancers like breast and prostate cancer, p21 expression and activity are largely governed by the transcriptional programs of estrogen or androgen receptor signaling. This hormonal regulation contributes to the control of tumor cell proliferation and underpins the initial efficacy of endocrine therapies. In contrast, as these diseases advance to late stages or evolve into non-hormone-dependent subtypes—exemplified by castration-resistant prostate cancer (CRPC) and specific forms of triple-negative breast cancer (TNBC)—these conventional hormonal control mechanisms often become dysfunctional or are entirely bypassed. This fundamental transition creates a critical therapeutic void, highlighting the urgent need to identify and exploit alternative molecular pathways to effectively target p21’s function. Promising strategies may include the precise modulation of its upstream transcriptional regulators, downstream effector proteins, or the intersecting parallel signaling networks that critically influence its activity. This review provides a systematic synthesis of the intricate and interconnected mechanisms that underpin the dual effects of p21 in sex hormone-related tumors. These mechanisms are categorized into three core, interrelated functional domains. (1) cell cycle regulation: p21 executes its canonical tumor-suppressive role by binding to and inhibiting cyclin-dependent kinases (CDKs) and by directly interacting with proliferating cell nuclear antigen (PCNA), thereby inducing cell cycle arrest, predominantly at the G1/S checkpoint; (2) apoptosis modulation: p21 exerts a highly context-dependent influence on programmed cell death, functioning either as a pro-apoptotic agent under severe genotoxic stress or as a pro-survival factor by inhibiting apoptosis through interactions with proteins like Bcl-2; (3) hormonal and signaling crosstalk: p21 is an integral node within broader cellular networks, engaging in direct physical interactions with hormone receptors(e.g., AR, ER) and participating in complex feedback loops with key oncogenic pathways, including PI3K/AKT, MAPK/ERK, and p53. Critically, the role of p21 is not static but highly dynamic. It can undergo a functional switch from tumor-suppressive to tumor-promoting in response to therapeutic pressures, metabolic alterations, or evolving tumor microenvironment cues. These adaptive shifts are frequently implicated in the development of therapy resistance and disease recurrence, particularly in advanced, hormone-resistant cancers. By synthesizing these insights, this review aims to establish a coherent theoretical framework to guide the future development of novel therapeutic strategies that target the p21 pathway. It underscores the necessity of moving beyond a simplistic, binary view of p21 and emphasizes the forthcoming challenges, such as the discovery of reliable biomarkers to predict its functional state and the rational design of context-specific pharmacological modulators to selectively harness its therapeutic potential.

To investigate the correlation between vitamin D nutritional status and insulin resistance in pubertal adolescents.

This study aimed to explore the effects and mechanisms of total extracts from Anthriscus sylvestris on pulmonary hypertension in rats. Sixty male SD rats were divided into normal(NC) group, model(M) group, positive drug sildenafil(Y) group, low-dose A. sylvestris(ES-L) group, medium-dose A. sylvestris(ES-M) group, and high-dose A. sylvestris(ES-H) group. On day 1, rats were intraperitoneally injected with monocrotaline(60 mg·kg~(-1)) to induce pulmonary hypertension, and the rat model was established on day 28. From days 15 to 28, intragastric administration of the respective treatments was performed. After modeling and treatment, small animal echocardiography was used to detect the right heart function of the rats. Arterial blood gas was measured using a blood gas analyzer. Hematoxylin and eosin(HE) staining and Masson staining were performed to observe cardiopulmonary pathological damage. Flow cytometry was used to detect apoptosis in the lung and myocardial tissues and reactive oxygen species(ROS) levels. Western blot was applied to detect the expression levels of transforming growth factor-β1(TGF-β1), phosphorylated mothers against decapentaplegic homolog 3(p-Smad3), Smad3, tissue plasminogen activator(t-PA), and plasminogen activator inhibitor-1(PAI-1) in lung tissue. A blood routine analyzer was used to measure inflammatory immune cell levels in the blood. Enzyme-linked immunosorbent assay(ELISA) was used to detect the expression levels of P-selectin and thromboxane A2(TXA2) in plasma. The results showed that, compared with the NC group, right heart hypertrophy index, right ventricular free wall thickness, right heart internal diameter, partial carbon dioxide pressure(PaCO_2), apoptosis in cardiopulmonary tissue, and ROS levels were significantly increased in the M group. In contrast, the ratio of pulmonary blood flow acceleration time(PAT)/ejection time(PET), right cardiac output, change rate of right ventricular systolic area, systolic displacement of the tricuspid ring, oxygen partial pressure(PaO_2), and blood oxygen saturation(SaO_2) were significantly decreased in the M group. After administration of the total extract of A. sylvestris, right heart function and blood gas levels were significantly improved, while apoptosis in cardiopulmonary tissue and ROS levels significantly decreased. Further testing revealed that the total extract of A. sylvestris significantly decreased the levels of interleukin-1β(IL-1β), interleukin-6(IL-6), and PAI-1 proteins in lung tissue, while increasing the expression of t-PA. Additionally, the extract reduced the levels of inflammatory cells such as leukocytes, lymphocytes, granulocytes, and monocytes in the blood, as well as the levels of P-selectin and TXA2 in plasma. Metabolomics results showed that the total extract of A. sylvestris significantly affected metabolic pathways, including arginine biosynthesis, tyrosine metabolism, and taurine and hypotaurine metabolism. In conclusion, the total extract of A. sylvestris may exert an anti-pulmonary hypertension effect by inhibiting the TGF-β1/Smad3 signaling pathway, thereby alleviating immune-inflammatory responses and thrombosis.
Animals ; Male ; Smad3 Protein/metabolism* ; Transforming Growth Factor beta1/metabolism* ; Rats, Sprague-Dawley ; Rats ; Signal Transduction/drug effects* ; Hypertension, Pulmonary/genetics* ; Thrombosis/immunology* ; Drugs, Chinese Herbal/administration & dosage* ; Humans ; Apoptosis/drug effects*

This study aims to investigate the molecular mechanism by which naringin alleviates cerebral ischemia/reperfusion(CI/R) injury through DRP1/LRRK2/MCU signaling axis. A total of 60 SD rats were randomly divided into the sham group, the model group, the sodium Danshensu group, and low-, medium-, and high-dose(50, 100, and 200 mg·kg~(-1)) naringin groups, with 10 rats in each group. Except for the sham group, a transient middle cerebral artery occlusion/reperfusion(tMCAO/R) model was established in SD rats using the suture method. Longa 5-point scale was used to assess neurological deficits. 2,3,5-Triphenyl tetrazolium chloride(TTC) staining was used to detect the volume percentage of cerebral infarction in rats. Hematoxylin-eosin(HE) staining and Nissl staining were employed to assess neuronal structural alterations and the number of Nissl bodies in cortex, respectively. Western blot was used to determine the protein expression levels of B-cell lymphoma-2 gene(Bcl-2), Bcl-2-associated X protein(Bax), cleaved cysteine-aspartate protease-3(cleaved caspase-3), mitochondrial calcium uniporter(MCU), microtubule-associated protein 1 light chain 3(LC3), and P62. Mitochondrial structure and autophagy in cortical neurons were observed by transmission electron microscopy. Immunofluorescence assay was used to quantify the fluorescence intensities of MCU and mitochondrial calcium ion, as well as the co-localization of dynamin-related protein 1(DRP1) with leucine-rich repeat kinase 2(LRRK2) and translocase of outer mitochondrial membrane 20(TOMM20) with LC3 in cortical mitochondria. The results showed that compared with the model group, naringin significantly decreased the volume percentage of cerebral infarction and neurological deficit score in tMCAO/R rats, alleviated the structural damage and Nissl body loss of cortical neurons in tMCAO/R rats, inhibited autophagosomes in cortical neurons, and increased the average diameter of cortical mitochondria. The Western blot results showed that compared to the sham group, the model group exhibited increased levels of cleaved caspase-3, Bax, MCU, and the LC3Ⅱ/LC3Ⅰ ratio in the cortex and reduced protein levels of Bcl-2 and P62. However, naringin down-regulated the protein expression of cleaved caspase-3, Bax, MCU and the ratio of LC3Ⅱ/LC3Ⅰ ratio and up-regulated the expression of Bcl-2 and P62 proteins in cortical area. In addition, immunofluorescence analysis showed that compared with the model group, naringin and positive drug treatments significantly decreased the fluorescence intensities of MCU and mitochondrial calcium ion. Meanwhile, the co-localization of DRP1 with LRRK2 and TOMM20 with LC3 in cortical mitochondria was also decreased significantly after the intervention. These findings suggest that naringin can alleviate cortical neuronal damage in tMCAO/R rats by inhibiting DRP1/LRRK2/MCU-mediated mitochondrial fragmentation and the resultant excessive mitophagy.
Animals ; Rats, Sprague-Dawley ; Reperfusion Injury/genetics* ; Flavanones/administration & dosage* ; Rats ; Dynamins/genetics* ; Male ; Brain Ischemia/genetics* ; Protein Serine-Threonine Kinases/genetics* ; Signal Transduction/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage*

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste

Fangcang shelter hospitals are modular, rapidly deployable facilities that play a vital role in pandemic response by providing centralized isolation and basic medical care for large patient populations. Artificial intelligence (AI) has the potential to transform Fangcang shelter hospitals into intelligent, responsive systems that are capable of significantly improving emergency preparedness, operational efficiency, and patient outcomes. Key application areas include site selection and design optimization, clinical decision support, AI-assisted clinical documentation and patient engagement, intelligent robotics, and operational management. However, realizing AI's full potential requires overcoming several challenges, including limited data accessibility, privacy and governance concerns, inadequate algorithmic adaptability in dynamic emergency settings, insufficient transparency and accountability in AI-driven decisions, fragmented system architectures due to proprietary formats, high costs disproportionate to the temporary nature of Fangcang shelter hospitals, and hardware reliability in austere environments. Addressing these challenges demands standardized data-sharing frameworks, development of explainable and robust AI algorithms, clear ethical and legal oversight, interoperable modular system designs, and active collaboration among multidisciplinary stakeholders.
Artificial Intelligence ; Humans ; Emergency Shelter ; China ; Hospitals ; COVID-19

OBJECTIVE: To evaluate the effectiveness of free medial femoral condyle (MFC) functional chimeric perforator flap (FCPF) transplantation in reconstructing joint function by repairing concomitant osteochondral defects and soft tissue defect in hand and foot joints. METHODS: A retrospective analysis was performed on 6 patients (5 males, 1 female; mean age of 33.4 years, range 21-56 years) with traumatic osteochondral joint defects and associated tendon, nerve, and soft tissue defects treated between January 2019 and November 2024. Defect locations included metacarpal heads (n=2), metacarpophalangeal joint (n=1), first metatarsal head (n=1), base of first proximal phalanx (n=1), and talar head (n=1), with soft tissue defects in all cases. Osteochondral defect sizes ranged from 1.5 cm×1.2 cm×0.7 cm to 4.0 cm×0.6 cm×0.6 cm, and skin defects ranged from 4 cm×3 cm to 13 cm×4 cm. The stage Ⅰ treatment included debridement, antibiotic-loaded bone cement filling of bone-cartilage defects, fracture internal fixation, and coverage with vacuum sealing drainage. Stage Ⅱ involved harvesting a free MFC- FCPF included an osteochondral flap (range of 1.5 cm×1.2 cm×0.7 cm to 4.0 cm×0.6 cm×0.6 cm), gracilis and/or semitendinosus tendon grafts (length of 4-13 cm), saphenous nerve graft (length of 3.5-4.0 cm), and a perforator skin flap (range of 6 cm×4 cm to 14 cm×6 cm), each with independent vascular supply. The flap was transplanted to reconstruct joint function. Donor sites were closed primarily or with skin grafting. Flap survival was monitored postoperatively. Radiographic assessment was used to evaluate bone/joint healing. At last follow-up, the joint function recovery was assessed. RESULTS: All 6 MFC-FCPF survived completely, with primary healing of wounds and donor sites. All patients were followed up 6-44 months (mean, 23.5 months). The flaps at metacarpophalangeal joint in 1 case and at ankle joint in 1 case were treated with degreasing repair because of their bulky appearance, while the other flaps had good appearance and texture. At 3 months after operation, the visual analogue scale (VAS) score for pain during joint movement of recipient site was 0-2, with an average of 0.7; at last follow-up, the VAS score of the donor site was 0-1, with an average of 0.3. According to the Paley fracture healing scoring system, the osteochondral healing of all the 6 patients was excellent. The range of motion of the metacarpophalangeal joint in 3 cases was 75%, 90%, and 100% of contralateral side respectively, the range of motion of the metatarsophalangeal joint in 2 cases was 65% and 95% of contralateral side respectively, and the range of motion of the ankle joint in 1 case was 90% of contralateral side. The hand function was evaluated as excellent in 2 cases and good in 1 case according to the upper limb function evaluation standard of the Chinese Medical Association Hand Surgery Society, and the foot function was evaluated as excellent in 2 cases and fair in 1 case according to the Maryland foot function score of 93, 91, and 69, respectively. The International Knee Documentation Committee (IKDC) score of 6 knees was 91-99, with an average of 95.2. CONCLUSION The free MFC-FCPF enables precise anatomical joint reconstruction with three-dimensional restoration of tendon, nerve, capsule, and soft tissue defects, effectively restoring joint function and improving quality of life.
Humans ; Male ; Adult ; Female ; Middle Aged ; Retrospective Studies ; Plastic Surgery Procedures/methods* ; Soft Tissue Injuries/surgery* ; Perforator Flap/blood supply* ; Femur/surgery* ; Young Adult ; Foot Joints/injuries* ; Treatment Outcome

OBJECTIVE: To explore the application effect of self-developed anatomical main nail insertion guide in proximal femoral nail antirotation (PFNA) internal fixation for the treatment of intertrochanteric fractures (IFF) in elderly patients. METHODS: A retrospective analysis was performed on 62 patients with AO31-A2 intertrochanteric fractures who underwent PFNA surgery and met the inclusion criteria from January 2022 to December 2024. They were divided into the conventional PFNA insertion group (conventional operation group) and the anatomical main nail insertion guide-assisted PFNA insertion group(guide group). The conventional operation group (PFNA) included 31 patients, 14 males and 17 females, the age ranged from 64 to 90 with an average of (75.2±11.6) years old;the guide group (PFNA) included 31 patients, 10 males and 21 females, the age ranged fron 67 to 97 with an average of (78.6±13.4) years old. The incision length of the main nail entry, the number of fluoroscopies from satisfactory reduction to before main nail insertion, operation time, intraoperative blood loss, 3-day postoperative VAS score, postoperative hip function Harris score, complications, etc. were observed and compared between the two groups. RESULTS: All patients were followed up for a period ranging from 4 to 12 months, with an average follow-up duration of (6.8±1.6) months. Compared with the guide group, the conventional operation group showed significant differences in the following parameters:the entrance length of the main screw was (6.74±3.77) cm vs. (5.13±1.31) cm, the number of fluoroscopies before the insertion of the main screw was (10.32±3.08) times vs. (7.71±2.41) times, the operation time was (150.45±53.47) minutes vs. (127.48±30.37) minutes, and the intraoperative blood loss was (196.77±121.06) ml vs. (140.97±86.00) ml, with P<0.05 indicating statistical significance.There was no statistically significant difference in 3-day postoperative VAS between the two groups (P>0.05). There was a statistically significant difference in the Harris scores between the conventional operation group and the guided operation group one month post-surgery (60.61±6.60) vs. (65.48±5.19) points (P<0.05). and there was no statistically significant difference in hip Harris scores between the two groups at 3 months after operation (P>0.05). During the 3-month follow-up after operation, neither group had incision infection, screw loosening, cutting, pressure sores, deep vein thrombosis, etc., and there was no statistically significant difference in the complication rate between the two groups. CONCLUSION It is quickly and accurately to implant PFNA assisted by the anatomical major nail implant guide in treatment of osteoporotic intertrochanteric fracture in the elderly.Compared with the traditional operation, it can shorten the operation time and reduce the surgical and X-ray trauma, and beneficial to the rapid rehabilitation of patients.
Humans ; Male ; Female ; Aged ; Hip Fractures/surgery* ; Bone Nails ; Retrospective Studies ; Aged, 80 and over ; Middle Aged ; Fracture Fixation, Intramedullary/instrumentation* ; Fracture Fixation, Internal/instrumentation*