Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

OBJECTIVE: To evaluate the clinical efficacy and safety of Yangxue Qingnao Pills (YXQNP) combined with amlodipine in treating patients with grade 1 hypertension. METHODS: This is a multicenter, randomized, double-blind, and placebo-controlled study. Adult patients with grade 1 hypertension of blood deficiency and Gan (Liver)-yang hyperactivity syndrome were randomly divided into the treatment or the control groups at a 1:1 ratio. The treatment group received YXQNP and amlodipine besylate, while the control group received YXQNP's placebo and amlodipine besylate. The treatment duration lasted for 180 days. Outcomes assessed included changes in blood pressure, Chinese medicine (CM) syndrome scores, symptoms and target organ functions before and after treatment in both groups. Additionally, adverse events, such as nausea, vomiting, rash, itching, and diarrhea, were recorded in both groups. RESULTS: A total of 662 subjects were enrolled, of whom 608 (91.8%) completed the trial (306 in the treatment and 302 in the control groups). After 180 days of treatment, the standard deviations and coefficients of variation of systolic and diastolic blood pressure levels were lower in the treatment group compared with the control group. The improvement rates of dizziness, headache, insomnia, and waist soreness were significantly higher in the treatment group compared with the control group (P<0.05). After 30 days of treatment, the overall therapeutic effects on CM clinical syndromes were significantly increased in the treatment group as compared with the control group (P<0.05). After 180 days of treatment, brachial-ankle pulse wave velocity, ankle brachial index and albumin-to-creatinine ratio were improved in both groups, with no statistically significant differences (P>0.05). No serious treatment-related adverse events occurred during the study period. CONCLUSIONS Combination therapy of YXQNP with amlodipine significantly improved symptoms such as dizziness and headache, reduced blood pressure variability, and showed a trend toward lowering urinary microalbumin in hypertensive patients. These findings suggest that this regimen has good clinical efficacy and safety. (Registration No. ChiCTR1900022470).
Humans ; Amlodipine/adverse effects* ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Hypertension/complications* ; Middle Aged ; Treatment Outcome ; Drug Therapy, Combination ; Adult ; Blood Pressure/drug effects* ; Double-Blind Method ; Aged ; Antihypertensive Agents/adverse effects*

The development of anticancer drugs to treat triple-negative breast cancer (TNBC) is an ongoing challenge. Immunogenic cell death (ICD) has garnered considerable interest worldwide as a promising synergistic modality for cancer chemoimmunotherapy. However, only few drugs or treatment modalities can trigger an ICD response and none of them exert a considerable clinical effect against TNBC. Therefore, new agents with potentially effective chemoimmunotherapeutic response are required. In this study, five new cyclometalated Ir(III) complexes containing isoquinoline alkaloid CˆN ligands were designed and synthesized. Among them, Ir-1 exhibited the highest in vitro cytotoxicity. Mechanistically, Ir-1 could trigger autophagy-dependent ferroptosis and a subsequent ferroptosis-dependent ICD response as well as indoleamine 2,3-dioxygenase (IDO) inhibition via reactive oxygen species (ROS)-mediated endoplasmic reticulum (ER) stress in MDA-MB-231 cells. When immunocompetent BALB/c mice were vaccinated with Ir-1-treated dying TNBC cells, antitumor CD8⁺ T-cell response and Foxp3⁺ T-cell depletion were induced, resulting in long-lasting antitumor immunity in TNBC cells. Moreover, combination therapy with Ir-1 and anti-PD1 could substantially augment in vivo therapeutic effects. Based on these results, Ir-1 is a promising candidate for chemoimmunotherapy against TNBC and its effects are mediated synergistically via ICD induction and IDO blockage.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.

Objective:To investigate the correlations of urinary adverse reactions with dose to the bladder and urethra during external pelvic irradiation for locally advanced cervical cancer.Methods:This study retrospectively collected relevant dosimetric parameters and urinary symptoms, such as frequent, urgent, and painful urination, from locally advanced cervical cancer patients treated with external pelvic irradiation in the Department of Oncology, Affiliated Hospital of Guizhou Medical University. The dosimetric parameters examined in this study included the maximum, minimum, and mean doses to bladder and urethra (i.e., Dmax, Dmin and Dmean), mean doses received in an area of 0.1, 1, and 2 cm 3 around the planning target volume, D0.1 cm 3, D1 cm 3, D2 cm 3, and percentages of irradiated volumes in the whole organ volume under doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy, V5 Gy, V10 Gy, V15 Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy, V50 Gy. Then the correlations between urinary symptoms and these dosimetric parameters were analyzed using the independent-sample t-test and the Logistic regression model. Results:The median volumes of bladder and urethra were 294.8 and 4.71 cm 3, respectively. Patients were divided into two groups based on the median division. The univariate analysis showed that urethral Dmax, Dmin, Dmean, V5 Gy, V10 Gy, V15Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy and V50 Gy correlated with urinary complications ( t = 14.30, 21.65, 32.19, 33.36, 16.62, 17.91, 21.52, 20.11, 12.27, 37.25, 30.18, 36.24 and 21.98, P<0.05). The multivariate analysis further indicates that urethral D2 cm 3, V20 Gy, V40 Gy and Bladder V40 Gy, D1 cm 3, D2 cm 3 were independent predictors of grade 2 urinary adverse reactions ( P<0.05). Conclusions:This study reported the correlations of relevant dosimetric parameters of urethra with urinary toxicity during external pelvic irradiation. It holds that urethral D2 cm 3, V20 Gy and V40 Gy should be restricted to minimize the risks of grade 2 urinary complications.

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) vs. concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC) patients with large tumor masses. Methods: LACC patients with localized tumor diameter >4 cm, were randomly allocated in an unblinded 1:1 ratio to NACT+CCRT or CCRT groups. Patients in the NACT+CCRT group were given paclitaxel combined with cisplatin (TP) NACT every 3 weeks for 2 cycles, followed by CCRT, with the chemotherapy regimen the same as for NACT. CCRT group were given CCRT with the same as for NACT. Results: From March 1, 2019, to June 30, 2021, 146 patients were included in the final analysis. Sixty-eight (93.2%) patients in the NACT+CCRT group and 66 (90.4%) patients in the CCRT group completed the expected treatment course. The complete response (CR) rate in the NACT+CCRT group was significantly higher than in the CCRT group (87.7% vs.67.6%, χ2 =54.540, p=0.000). In the NACT+CCRT group, the 1- and 2-year overall survival (OS) rates were significantly higher than those in the CCRT group (96% vs. 89% and 89% vs. 79%, χ2 =5.737, p=0.017). Additionally, the rate of recurrences and distant metastases was significantly lower in the NACT+CCRT group than in the CCRT group (4.11% vs. 7.35%, χ2 =4.059, p=0.021). Most treatment-related adverse events in both groups were grade 3. Conclusion Compared to CCRT, NACT+CCRT might improve the treatment completion rate, increase CR rate and 1- and 2-year OS rates, and reduce distant metastases rate for LACC patients with large tumor masses.

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) vs. concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC) patients with large tumor masses. Methods: LACC patients with localized tumor diameter >4 cm, were randomly allocated in an unblinded 1:1 ratio to NACT+CCRT or CCRT groups. Patients in the NACT+CCRT group were given paclitaxel combined with cisplatin (TP) NACT every 3 weeks for 2 cycles, followed by CCRT, with the chemotherapy regimen the same as for NACT. CCRT group were given CCRT with the same as for NACT. Results: From March 1, 2019, to June 30, 2021, 146 patients were included in the final analysis. Sixty-eight (93.2%) patients in the NACT+CCRT group and 66 (90.4%) patients in the CCRT group completed the expected treatment course. The complete response (CR) rate in the NACT+CCRT group was significantly higher than in the CCRT group (87.7% vs.67.6%, χ2 =54.540, p=0.000). In the NACT+CCRT group, the 1- and 2-year overall survival (OS) rates were significantly higher than those in the CCRT group (96% vs. 89% and 89% vs. 79%, χ2 =5.737, p=0.017). Additionally, the rate of recurrences and distant metastases was significantly lower in the NACT+CCRT group than in the CCRT group (4.11% vs. 7.35%, χ2 =4.059, p=0.021). Most treatment-related adverse events in both groups were grade 3. Conclusion Compared to CCRT, NACT+CCRT might improve the treatment completion rate, increase CR rate and 1- and 2-year OS rates, and reduce distant metastases rate for LACC patients with large tumor masses.

Objective: To compare the efficacy and safety of neoadjuvant chemotherapy combined with concurrent chemoradiotherapy (NACT+CCRT) vs. concurrent chemoradiotherapy (CCRT) in locally advanced cervical cancer (LACC) patients with large tumor masses. Methods: LACC patients with localized tumor diameter >4 cm, were randomly allocated in an unblinded 1:1 ratio to NACT+CCRT or CCRT groups. Patients in the NACT+CCRT group were given paclitaxel combined with cisplatin (TP) NACT every 3 weeks for 2 cycles, followed by CCRT, with the chemotherapy regimen the same as for NACT. CCRT group were given CCRT with the same as for NACT. Results: From March 1, 2019, to June 30, 2021, 146 patients were included in the final analysis. Sixty-eight (93.2%) patients in the NACT+CCRT group and 66 (90.4%) patients in the CCRT group completed the expected treatment course. The complete response (CR) rate in the NACT+CCRT group was significantly higher than in the CCRT group (87.7% vs.67.6%, χ2 =54.540, p=0.000). In the NACT+CCRT group, the 1- and 2-year overall survival (OS) rates were significantly higher than those in the CCRT group (96% vs. 89% and 89% vs. 79%, χ2 =5.737, p=0.017). Additionally, the rate of recurrences and distant metastases was significantly lower in the NACT+CCRT group than in the CCRT group (4.11% vs. 7.35%, χ2 =4.059, p=0.021). Most treatment-related adverse events in both groups were grade 3. Conclusion Compared to CCRT, NACT+CCRT might improve the treatment completion rate, increase CR rate and 1- and 2-year OS rates, and reduce distant metastases rate for LACC patients with large tumor masses.