[Objective] : To systematically evaluate the overall efficacy of external application of traditional Chinese medicine (EA-TCM) in combination with oral three-step analgesic ladder therapy for patients suffering from cancer-induced bone pain (CIBP). [Methods] : We conducted a literature search of randomized controlled trials on the combination of EA-TCM and three-step analgesic ladder therapy for CIBP across ten databases and two registration systems. It included four Chinese databases [Chinese Biomedical Literature Database (SinoMed), China National Knowledge Infrastructure (CNKI), Wanfang Database, and China Science and Technology Journal Database (VIP) ], six English databases (Scopus, Embase, Web of Science, PubMed, Cochrane Library, and OpenGrey), and two registration systems (Chinese Clinical Trial Registry and ClinicalTrials.gov). The timeframe for the literature search extended from the inception of each database to December 31, 2023. Meta-analysis was performed using RevMan (v5.4.1), and the outcome indicators (pain relief rate, analgesic duration, quality of life, pain intensity, breakthrough pain frequency, and adverse reactions) were graded using GRADE profiler (v3.6). [Results] : According to the established inclusion and exclusion criteria, a total of 43 studies was deemed eligible, involving 3 142 participants with CIBP. The results of meta-analysis showed that compared with oral three-step analgesic ladder therapy alone, the combined therapy of EA-TCM and three-step analgesic ladder has a significant improvement in pain relief rate [risk ratio (RR) = 1.32, 95% confidence interval (CI): 1.24 to 1.41, P < 0.000 01], analgesic duration [mean difference (MD) = 1.33, 95% CI: 0.97 to 1.69, P < 0.000 01], and quality of life (MD = 5.66, 95% CI: 4.88 to 6.44, P < 0.000 01). Furthermore, the combined therapy significantly reduced pain intensity (MD = – 1.00, 95% CI: – 1.19 to – 0.80, P < 0.000 01), breakthrough pain frequency (MD = – 0.43, 95% CI: – 0.51 to – 0.36, P < 0.000 01), and adverse reactions (RR = 0.60, 95% CI: 0.53 to 0.68, P < 0.000 01) in CIBP patients. Based on the GRADE assessment, the level of evidence varied from low to moderate. [Conclusion] EA-TCM combined with the three-step analgesic ladder therapy can effectively alleviate pain symptoms in patients with CIBP and improve their quality of life. Additionally, the EA-TCM can effectively reduce the incidence of adverse reactions associated with three-step analgesic therapy.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objectives: Hypoparathyroidism (HP) is a rare endocrine disorder caused by parathyroid hormone (PTH) defi ciency. The PTH is a candidate gene for familial isolated hypoparathyroidism (FIH). This study aimed to investigate the pathogenicity of two novel rare variants (RVs) ofPTH through in vitro functional study. Methods: Targeted next-generation sequencing was used to identify candidate gene mutations. Clinical data were retrospectively collected. Wild-type (WT) PTH was used as a template for site-directed mutagenesis to create mutant eukaryotic expression plasmids, which were transfected into cells. Treated with or without 4-phenylbu tyric acid (4-PBA), the levels of intact PTH (iPTH) and PTH (1-84) were measured by chemiluminescence, and protein expression was assessed using Western blotting. Results: Two patients carrying PTH mutations (c.154G > A: p.Val52Ile, c.270G > T: p.Leu90Phe) were identified.Patient 1, a 45-year-old male, presented with carpal and pedal numbness, muscle cramps, and low serum calcium (1.29 mmol/L). Patient 2, a 12-year-old female, had muscle twitches, convulsions, low calcium (1.50 mmol/L), and iPTH of 4 pg/mL. The iPTH or PTH (1-84) levels in the medium transfected with mutant Val52Ile and Leu90Phe PTH decreased by 31%–38%, and 51%–96% compared to WT (allP < 0.05), which were not rescued by 4-PBA. No significant changes in intracellular PTH expression were observed. Conclusions In this study, two novel RVs of PTH(Val52Ile and Leu90Phe) were identified that may impair hormone synthesis and secretion. Our study has broadened the mutation spectrum of the PTH and shed light on potential mechanisms underlying FIH.

Objective:To conduct a comprehensive review on the current research status of postpartum follow-up for patients with hypertensive disorders of pregnancy (HDP), and provide a basis and guidance for the management of postpartum follow-up for HDP patients.Methods:Guided by the methodological framework of the scoping review, the literatures on postpartum follow-up of HDP patients in Cochrane Library, PubMed, Web of Science, Embase, China Biomedical Literature Database, China National Knowledge Infrastructure, VIP and Wanfang databases were retrieved, and search for relevant literature by the snowballing method. The search time range is from the establishment of the database to February 1, 2025. The included literature was analyzed and summarized.Results:A total of 32 literatures were included, including 31 in English and 1 in Chinese. The participation rate of postpartum follow-up for HDP patients is generally low, and the disease has a significant impact on long-term health. In addition, there is considerable variation in the content, format and time of follow-up. The follow-up content includes the patient's physical health status, long-term health risks and the availability of medical resources, etc.Conclusions:There are still deficiencies in the current implementation of postpartum follow-up for HDP patients. Existing follow-up studies lack high-quality randomized controlled trials as evidence support, and the influencing factors are complex and diverse. In the future, it is necessary to strengthen cooperation among multiple disciplines, closely integrate clinical guidelines with practical needs, and systematically evaluate the effectiveness of follow-up in clinical practice to enhance the scientific and effectiveness of follow-up and provide better health management support for HDP patients.

Objective To analyze the relationship between serum angiopoietin-like protein 8(ANGPTL8)and semaphorin 3A(Sema 3A)levels and postoperative cerebral vasospasm(CVS)in patients with intracranial aneurysm(IA)rupture.Methods A total of 188 patients with IA rupture receiving surgical treatment in our hospital were prospectively selected during October 2021 and October 2023,and according to whether CVS occurred after surgery,they were classified into a spasm group(75 cases)and a non-spasm group(113 cases).Serum ANGPTL8 and Sema 3A levels were measured after admission.Spearman correlation analysis was performed to assess the correlation of the levels with CVS occurrence.Binary logistic regression analysis was applied to construct a prediction model with serum ANGPTL8 and Sema 3A as variables.ROC curve was plotted to evaluate the predictive value of the levels for postoperative CVS.Results The serum ANGPTL8 level was significantly higher while that of Sema 3A was obviously lower in the spasm group then the non-spasm group(P＜0.01).Binary logistic regression analysis showed that the levels of serum ANGPTL8 and Sema 3A were independent predictors of postoperative CVS in patients with ruptured IA(OR=1.021,95％CI:1.013-1.029,P=0.000;OR=0.980,95％CI:0.967-0.993,P=0.003).ROC curve analysis indicated that the AUC value,sensitivity and speci-ficity of the two indicators combined together in predicting postoperative CVS was 0.939(95％CI:0.894-0.969),89.33％and 89.38％,respectively,with better predictive efficiency than each indicator alone(P＜0.01).Conclusion Serum ANGPTL8 and Sema 3A levels are closely associat-ed with postoperative CVS in patients with IA rupture,and they can be used as effective indicators for early prediction of postoperative CVS.

Background:To compare the efficacy and safety of monthly administrations of gonadotropin releasing hormone (GnRH) agonists LY01005 and Zoladex ? in Chinese patients with premenopausal breast cancer. Methods:From October 2020 to November 2021, 188 premenopausal breast cancer patients were enrolled in 34 hospitals and randomized 1:1 to receive either LY01005 or Zoladex ? every 28 days for a total of three injections. All patients concomitantly received oral tamoxifen (TAM). The primary efficacy endpoint was cumulative probability of maintaining menopausal level [oestradiol (E2) ≤30 pg/ml] from day 29 to day 85. The second efficacy endpoint included changes in E2, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) compared with the baseline. Pharmacokinetics (PK), pharmacodynamics (PD), and safety were analyzed. The study also evaluated the pharmacokinetic and pharmacodynamic characteristics of LY01005. Results:A total of 188 patients were randomised and 187 patients received either LY01005 or Zoladex ?. Cumulative probabilities of maintaining menopausal level (E2≤30 pg/ml) from day 29 to day 85 were 93.1% for LY01005 and 86.3% for Zoladex ?. The between-group difference was 6.8% (95% CI: -2.3%, 15.9%) and primary efficacy in the LY01005 group was not inferior to that in the Zoladex ? group. Changes in E2, LH, and FSH levels compared with the baseline were equivalent between the two groups (E2: 89.34% to 90.23% vs. 82.11% to 85.02%; LH: 88.89% to 95.52% vs. 89.70% to 97.02%; FSH: 75.36% to 80.85% vs.73.07% to 80.24%, respectively). After three consecutive doses of LY01005, the LH and FSH levels of the subjects showed a transient increase after the first dose, reached a peak on the second day and then started to decrease. The LH and FSH reached a lower level and remained at or below that level until the 85th day. Both treatments were well-tolerated. Conclusion:LY01005 is as effective as Zoladex ? in suppressing E2 to menopausal levels in Chinese patients with premenopausal breast cancer, with a similar safety profile.

Objective:To evaluate the efficacy and safety of therapeutic temperature control in patients with severe traumatic brain injury (sTBI).Methods:The full-text databases of Chinese Medical Journal, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP Database, China Biomedical Database, PubMed, Embase, and Cochrane Library were searched for randomized controlled trials (RCTs) of hypothermia treatment and conventional treatment in patients with sTBI. The search period was from January 2016 to June 2025. Meta-analysis was performed using RevMan 5.3 software. The evaluation indicators included intracranial pressure before treatment, at 3 and 5 days after treatment, favorable prognosis rate and mortality rate within 6 months after treatment, and incidence of pulmonary infection, intracranial infection, epilepsy, acute gastrointestinal dysfunction, deep vein thrombosis, abnormal coagulation function, and arrhythmia during treatment; publication bias.Results:A total of 33 studies involving 3 322 patients were included, with 1 696 patients in the temperature treatment group and 1 626 in the conventional treatment group. There was no statistically significant difference in intracranial pressure between the two groups before treatment ( SMD=0, 95% CI -0.13, 0.14, P>0.05). However, at 3 and 5 days after treatment, the intracranial pressure was lower in the temperature treatment group than that in the conventional treatment group ( SMD=-2.29, 95% CI -2.76, -1.82, P<0.01; SMD=-2.66, 95% CI -3.43, -1.89, P<0.01). Within 6 months after treatment, the favorable prognosis rate was higher in the temperature treatment group than that in the conventional treatment group ( RR=1.41, 95% CI 1.32, 1.50, P<0.01), and mortality rate was lower than that in the conventional treatment group ( RR=0.64, 95% CI 0.55, 0.75, P<0.01). Compared with the conventional treatment group, the incidences of epilepsy and acute gastrointestinal dysfunction in the temperature treatment group were statistically reduced ( RR=0.33, 95% CI 0.13, 0.83, P<0.05; RR=0.43, 95% CI 0.25, 0.74, P<0.05). There were no statistically significant differences in the incidence of pulmonary infection ( RR=0.96, 95% CI 0.85, 1.08, P>0.05), intracranial infection ( RR=0.56, 95% CI 0.20, 1.56, P>0.05), deep vein thrombosis ( RR=0.93, 95% CI 0.69, 1.25, P>0.05), abnormal coagulation function ( RR=1.19, 95% CI 0.43, 3.31, P>0.05) or arrhythmia ( RR=0.51, 95% CI 0.23, 1.12, P>0.05) between the two groups. Egger′s test indicated the presence of publication bias and the results remained robust after trim and fill analysis. Conclusions:For patients with sTBI, temperature control therapy shows lowered intracranial pressure and mortality rate as well as improved favorable prognosis rate at 6 months posttreatment, and decreased incidence of epilepsy and acute gastrointestinal dysfunction during treatment, while reveals similar incidence of pulmonary infection, intracranial infection, deep vein thrombosis, abnormal coagulation function, and arrhythmia when compared with conventional treatment.

Objective To perform a regression analysis on the predictive value of serum micro-RNAs(miR)for early neurological deterioration(END)in patients with branch atheromatous dis-ease(BAD).Methods A total of 134 BAD patients admitted in our department from February 2020 to February 2023 were enrolled,and according to the END status,they were divided into de-terioration group(28 cases)and non-deterioration group(106 cases).Serum levels of miR-130a,miR-210,miR-141-3p and miR-29a-3p were measured at admission.NIHSS score was used to eval-uate the END status at admission and at 7 d after admission.Binary logistic regression analysis was adopted to construct a model of above four miRs in predicting END in BAD patients.ROC curve was plotted to assess the predictive value of the four miRs alone or combined together for END.Results The serum levels of miR-130a and miR-210 were significantly higher,while those of miR-141-3p and miR-29a-3p were obviously lower in the deterioration group than the non-deterioration group(P＜0.01).Logistic regression analysis indicated that serum miR-130a,miR-210,miR-141-3p and miR-29a-3p were independent predictors of END in BAD patients(P＜0.05,P＜0.01).ROC curve analysis showed that the AUC value of the four miRs combined together in predicting END in BAD patients was 0.977(95％CI:0.936-0.995),with a sensitivity of 96.43％and a specificity of 90.57％,and the combined detection exhibited better predictive effi-ciency than each indicator alone(P＜0.01).Conclusion Serum miR-130a,miR-210,miR-141-3p and miR-29a-3p have certain value in predicting END in BAD patients,and their combined detec-tion can enhance its predictive efficiency.