[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.

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 study the improvement effect and mechanism of Shengmai powder on heart failure （HF） mice with qi-yin deficiency. METHODS The mice were randomly divided into blank group （water）， model group （water）， Shengmai powder low-， medium-， and high-dose groups [2.61， 5.22 and 10.44 g/kg （based on crude drug dosage）] and positive control group （metoprolol， 30 mg/kg）， with 10 mice in each group. Except for the blank group， all other groups were subcutaneously injected with D-galactose， and a qi-yin deficiency HF mice model was established by continuous food restriction and weight-bearing swimming. At the same time of modeling， the corresponding medicine/water was gavaged once a day for five weeks. The general state of mice was recorded and the traditional Chinese medicine （TCM） syndrome score was evaluated. Behavioral experiments were conducted to investigate the total distance of open field action， the percentage of immobility time， and the swimming exhaustion time of mice. The contents of aspartate transaminase （AST）， creatine kinase （CK） and lactate dehydrogenase （LDH） in the serum of mice were detected； cardiac function indexes [heart rate， left ventricular ejection fraction （LVEF）， left ventricular end systolic diameter （LVESD）， left ventricular end diastolic diameter （LVEDD）， left ventricular mass index and whole heart mass index] were all detected； the histopathological morphology of mice myocardium was observed； the level of cardiomyocyte apoptosis in mice was detected； mRNA expression levels of B-cell lymphoma 2 （Bcl-2）， Bcl-2 associated X protein （Bax）， and Cleaved-caspase-3 in myocardial tissue of mice were detected； the phosphorylation levels of sarcoplasmic reticulum calcium regulatory related proteins [ryanodine receptor 2 （RyR2） and phospholamban （PLB）] in myocardial tissue of mice were detected. RESULTS Compared with the blank group， the body weight， total distance of open field action， swimming exhaustion time， LVEF， LVEDD， Bcl-2 mRNA expression level in myocardial tissue and PLB protein phosphorylation level in the model group were significantly reduced/shortened （P＜0.05）； TCM syndrome score， the percentage of immobility time， heart rate， LVESD， left ventricular mass index， whole heart mass index， cardiomyocyte apoptosis rate， the contents of CK， LDH and AST in serum， mRNA expression levels of Cleaved-caspase-3 and Bax and the phosphorylation level of RyR2 protein in myocardial tissue were significantly increased （P＜0.05）； there were inflammatory cell infiltration， disordered cell arrangement and obvious myocardial interstitial fibrosis in myocardial tissue. After the intervention of Shengmai powder， most of the above quantitative indexes in mice were significantly reversed （P＜0.05）， the inflammatory cell infiltration in myocardial tissue was reduced， and the degree of fibrosis was significantly reduced. CONCLUSIONS Shengmai powder can improve cardiac function， reduce the level of cardiomyocyte apoptosis and myocardial fibrosis in HF mice with qi-yin deficiency. Its mechanism may be related to the regulation of the expression of sarcoplasmic reticulum calcium regulation related proteins.

Objective:To explore brain network properties and their relationship with cognitive function in children with spastic cerebral palsy (SCP) using diffusion tensor imaging (DTI) based graph theory analysis.Methods:The study was a cross-sectional study. Clinical and imaging data of 21 children with SCP (SCP group) and 32 healthy children (control group) who underwent cranial MRI at the Affiliated Hospital of Zunyi Medical University from August 2020 to April 2022 were analyzed retrospectively. 3D-T 1WI, DTI and Wechsler Intelligence Scale were assessed for all subjects. The Wechsler Intelligence Scale included the verbal comprehension index (VCI), the processing speed index (PSI), the work memory index (WMI), and the perceptual reasoning index (PRI), etc., and ultimately the full scale intelligence quotient (FSIQ) scores were obtained based on the indices of each subscale. Independent samples t-test was used to analyze the differences in the small world attributes [small-world index (σ), normalized shortest path length (λ), normalized clustering coefficients (γ)], global attributes [global efficiency (Eglob), local efficiency (Eloc), characteristic path length (Lp), clustering efficiency (Cp)] and node attributes [degree centrality(DC), nodal efficiency (Ne), betweeness centrality (Bc), nodal shortest path length (NLp), nodal clustering efficiency, nodal local efficiency] between two groups of children′s brain networks. Brain network indicators with statistically significant differences between the 2 groups were correlated with Wechsler Intelligence Scale scores using Spearman. Results:The FSIQ scores on the Wechsler Intelligence Scale and the VCI, WMI, PSI, and PRI were lower in the SCP group than in the control group, and the differences were all statistically significant (all P<0.05). Both groups of children′s brain networks had small world properties. Compared with the control group, Eglob decreased, Lp and λ increased in the SCP group (all P<0.05). Compared with the control group, DC and Ne in multiple brain regions decreased, NLp increased in the SCP group (all P<0.05, FDR corrected). Correlation analysis showed that DC in the right parsopercularis was positively correlated with FSIQ, VCI, WMI and PRI( r=0.53, 0.47, 0.47, 0.60, P=0.019, 0.045, 0.044, 0.020, respectively); NLp in the right parsopercularis was negatively correlated with PRI( r=-0.56, P=0.030); Ne in left paracentral, the right parsopercularis, right precentral, right postcentra were positively correlated with PRI( r=0.62, 0.56, 0.53, 0.54, P=0.015, 0.031, 0.044, 0.039, respectively); Ne in the right precentral was positively correlated with WMI ( r=0.48, P=0.039) in the SCP group. Conclusions:There are changes in the topological attributes of global and multiple regional brain networks in SCP. The changes in the attributes of nodes in the right parsopercularis, right precentral, right postcentral, and left paracentral could reflect cognitive dysfunction in children with SCP.

ObjectiveTo explore the law of women reproductive aging based on theory of "seven-year period" in traditional Chinese medicine（TCM） through analyzing the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. MethodsThe data of female who visited Guangdong Provincial Hospital of Traditional Chinese Medicine from January 2018 to December 2022 and accepted basic hormone and anti-müllerian hormone determination were collected retrospectively. According to the age of subjects， they were divided into the "1-2 seven" group （under 21 years old）， "3 seven" group （21-27 years old）， "4 seven" group （28-34 years old）， "5 seven" group （35-41 years old）， "6 seven" group （42-48 years old） and "7 seven" and older group （49 years old and above）. The age， average menstrual cycle in the past 3 months， basic hormone levels including follicle stimulating hormone （FSH）， luteinizing hormone （LH）， estradiol （E₂）， testosterone （T） and FSH/LH value， and anti-müllerian hormone （AMH） levels were collected and compared. ResultsA total of 1221 cases were included. The differences in FSH， LH， FSH/LH values， E₂， T， AMH levels and average menstrual cycle among the groups were statistically significant （P＜0.05 or P＜0.01）. AMH peaked in the "3 seven" group. Compared to those in the "3 seven" group， the FSH/LH value in the "4 seven" group increased， while the LH， AMH and T levels decreased， and the menstrual cycle was shortened （P＜0.01）. The FSH/LH， LH， AMH， T and menstrual cycle in the "5 seven" group were consistent with the changing trend of those in the "4 seven" group， while the FSH and E₂ levels in the "5 seven" group were significantly higher （P＜0.05 or P＜0.01）. Compared to those in the "5 seven" group， the FSH， LH and E₂ levels of the "6 seven" group increased， and the AMH and T levels continued to decrease （P＜0.05 or P＜0.01）. Compared to those in the "6 seven" group， the FSH and LH levels of the "7 seven" and older group continued to increase， and the AMH and E₂ levels decreased （P＜0.01）. ConclusionThe law of women reproductive aging in the "seven-year period" theory is basically consistent with the characteristics of basic sex hormone levels and anti-müllerian hormone levels in women of different ages. The reproductive capacity reaches its peak in the "three-seven-year period" and gradually moves towards reproductive aging in the "four-seven-year period".

Objective To explore the targets and pathways of Cynanchum wilfordii for treatment of ulcerative colitis(UC).Methods UPLC-QE-MS was used to identify the components of Cynanchum wilfordii ethanol extract,and their targets were screened using public databases for construction of the core protein-protein interaction(PPI)network and GO and KEGG enrichment analyses.Forty male C57 mice were randomized into normal control group,model group,mesalazine group and Cynanchum wilfordii group(n=10),and in the latter 3 groups,mouse UC models were established by treatment with 2.5%DSS and the latter 2 groups drug interventions by gavage.The therapeutic effect was evaluated by recording body weight changes and DAI score.Pathological changes of the colon tissue were observed with HE and AB-PAS staining,and JAK2 and STAT3 protein expressions were detected with Western blotting.The metabolites and metabolic pathways were identified by metabonomics analysis.Results We identified 240 chemical components in Cynanchum wilfordii alcoholic extracts,including 19 steroids.A total of 177 Cynanchum wilfordii targets,5406 UC genes,and 117 intersection genes were obtained.JAK2 and STAT3 were the core targets and significantly enriched in lipid and atherosclerosis pathways.Cynanchum wilfordii treatment significantly increased the body weight and decreased DAI score of UC mice(P<0.05),alleviated intestinal pathologies,and decreased JAK2 and STAT3 protein expressions in the colon tissues.Most of the 83 intersecting differential metabolites between the control,model and Cynanchum wilfordii groups were identified as glycerophospholipids,arachidonic acid,and amino acids involving glycerophospholipid metabolism and other pathways.Correlation analysis suggested that the core targets of Cynanchum wilfordii for UC participated in regulation of the metabolites.Conclusion Cynanchum wilfordii alleviates lipid and amino acid metabolism disorders to lessen UC in mice by regulating the core targets including JAK2 and STAT3 and the levels of endogenous metabolites.