OBJECTIVES: To explore the active components that mediate the therapeutic effect of Centella asiatica on psoriasis and their therapeutic mechanisms. METHODS: TCMSP, TCMIP, PharmMapper, Swiss Target Prediction, GeneCards, OMIM and TTD databases were searched for the compounds in Centella asiatica and their targets and the disease targets of psoriasis. A drug-active component-target network and the protein-protein interaction network were constructed, and DAVID database was used for pathway enrichment analysis. In a RAW264.7 macrophage model of LPS-induced inflammation, the anti-inflammatory effect of 7.5, 15, 30, and 60 μmol/L quercetin, asiaticoside, and asiatic acid, which were identified as the main active components in Centella asiatica, were tested by measuring cellular production of NO, TNF‑α and IL-6 using Griess method and ELISA and by detecting mRNA expressions of IL-23, IL-17A, TNF-α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727) with RT-qPCR and Western blotting. RESULTS: A total of 139 targets of Centella asiatica and 4604 targets of psoriasis were obtained, and among them CASP3, EGFR, PTGS2, and ESR1 were identified as the core targets. KEGG analysis suggested that quercetin, asiaticoside, and asiatic acid in Centella asiatica were involved in cancer and IL-17 and MAPK signaling pathways. In the RAW264.7 macrophage model of inflammation, treatment with quercetin significantly reduced cellular production of NO, TNF‑α and IL-6, and lowered mRNA expressions of IL-23, IL-17A, TNF‑α and IL-6 and protein expressions of p-STAT3 (Tyr705) and p-STAT3 (Ser727). CONCLUSIONS Quercetin, asiaticoside and asiatic acid are the main active components in Centella asiatica to mediate the therapeutic effect against psoriasis, and quercetin in particular is capable of suppressing cellular production of NO, TNF‑α and IL-6 and regulating the IL-23/IL-17A inflammatory axis by mediating STAT3 phosphorylation to inhibit inflammatory response.
Quercetin/pharmacology* ; Psoriasis/metabolism* ; STAT3 Transcription Factor/metabolism* ; Mice ; Animals ; Centella/chemistry* ; Triterpenes/pharmacology* ; Phosphorylation ; Interleukin-17/metabolism* ; Interleukin-23/metabolism* ; RAW 264.7 Cells ; Pentacyclic Triterpenes/pharmacology* ; Macrophages/drug effects* ; Signal Transduction ; Plant Extracts

Pheochromocytomas and paragangliomas are rare but therapeutically challenging neuroendocrine tumors in urology. Surgical treatment has been recognized as a definitive treatment. However, traditional surgical methods present certain risks and limitations. The Da Vinci robotic surgery offers a new approach for treating these tumors. This review elucidates the technical features, clinical applications, and treatment outcomes of Da Vinci robotic surgery and the progress in the treatment of pheochromocytomas and paragangliomas. In addition, this review discusses the prospects of combining Da Vinci robotic surgery with other emerging technologies, emphasizing the further research to validate its long-term efficacy and safety.

Pheochromocytomas and paragangliomas are rare but therapeutically challenging neuroendocrine tumors in urology. Surgical treatment has been recognized as a definitive treatment. However, traditional surgical methods present certain risks and limitations. The Da Vinci robotic surgery offers a new approach for treating these tumors. This review elucidates the technical features, clinical applications, and treatment outcomes of Da Vinci robotic surgery and the progress in the treatment of pheochromocytomas and paragangliomas. In addition, this review discusses the prospects of combining Da Vinci robotic surgery with other emerging technologies, emphasizing the further research to validate its long-term efficacy and safety.

Objective:To explore the clinical data of patients with metastatic pheochromocytoma/paraganglioma (PPGL).Methods:The clinical data of 57 patients with metastatic pheochromocytoma/paraganglioma diagnosed and treated at Peking Union Medical College Hospital from January 2016 to June 2022 were reviewed, including 28 cases of pheochromocytoma(PCC) and 29 cases of paraganglioma(PGL). The clinical manifestations, biochemical indexes, tumour characteristics, and metastatic characteristics of the 57 patients were analysed.Results:There were 34 males and 23 females. The median age at the time of initial diagnosis was 34 (20, 54) years, 17 (29.3%) presented with concurrent metastases, and 40 (70.7%) with heterochronous metastases. The median time to presentation of metastases was 2.2 (0, 5.0) years (range 0-22 years). Adrenergic symptoms were present in 45 cases (78.6%) at the time of initial diagnosis, and the median size of the primary tumour was 6.7 (5.0, 9.0) cm. Excessive catecholamine secretion was present in 48 cases (81.4%). The most common locations of metastasis were lymph nodes (71.9%, 41/57), bone (47.3%, 27/57), lung (38.6%, 20/57), and liver (35.1%, 20/57). Metastatic PGL had more multifocal metastases than PCC [10 (34.5%) vs. 2 (7.1%), P=0.011)], was more frequently associated with SDHB mutations [13 (42.9%) vs. 3 (10.7%), P=0.008], and was more likely to have concurrent metastases [12 (41.3%) vs. 5 (17.9%), P=0.005]. Metastatic PCC primary tumours were larger compared to PGL [median length 8.9 (4.0, 17.0) cm vs. 6.1 (1.0, 15.8) cm, P=0.020]. Conclusions:Patients with PGL present with metastases over an extremely wide time span, and patients diagnosed with PPGL should be followed throughout their lives. PGL is more prone to multifocal metastases and simultaneous metastases than PCC, and PGL is more highly correlated with the SDHB mutation.

Objective:To investigate the effects of self-made Gujin Xiaoji Mixture combined with warming needle therapy on the clinical efficacy and immune function of patients with advanced non-small cell lung cancer (NSCLC) with qi and yin deficiency syndrome.Methods:This experiment was a randomized controlled trial study. 180 patients with advanced NSCLC qi and yin deficiency syndrome in the oncology centre of Qingdao Hospital of Traditional Chinese Medicine were selected as the observation subjects from March 2021 to August 2022, and were divided into 2 groups using the random number table method, with 90 cases in each group. The control group received conventional chemotherapy combined with Sintilimab injection, 21 days as a cycle, with a total of 4 cycles of treatment; and the observation group received Gujin Xiaoji Mixture combined with warming needle therapy based on the control group, 7 days as one course of treatment, with a total of 12 courses. Both groups were followed up for 12 months. The TCM syndrome scores were performed before and after treatment. The functional assessment of cancer therapy-lung (FACT-L) was used to evaluate the quality of life of patients; flow cytometry was used to detect the levels of CD3 +, CD4 +, CD8 + and NK cell, and the CD4 +/CD8 + ratio was calculated; adverse drug reactions and progression free survival of patients during treatment were observed and recorded, the efficacy of TCM syndrome and objective efficacy of solid tumors were evaluated. Results:After treatment, the observation group's post-treatment TCM syndrome score (5.67±1.99 vs. 7.12±2.31, t=-4.53) was lower than that of the control group ( P<0.001); mobility (23.03±2.80 vs. 20.69±2.46, t=5.96), daily living (23.06±2.56 vs. 20.71± 2.33, t=6.42), emotional status (18.44±2.32 vs. 16.12±2.71, t=6.18), and other factors (33.14±4.11 vs. 27.39±4.64, t=8.81) and total score (97.68±7.23 vs. 84.91±7.49, t=11.64) were higher than those in the control group ( P<0.01). In the observation group, after treatment, the levels of CD3 + [(65.14±6.06)% vs. (59.84±5.74)%, t=6.02], CD4 + [(40.09±4.09)% vs. (35.69±3.86)%, t=7.43], NK cell [(29.11±4.81)% vs. (22.38±4.51)%, t=9.68] and CD4 +/CD8 + [(1.52±0.27) vs. (1.14±0.12), t=12.63] were higher than those in the control group ( P<0.01), and CD8 + [(26.82±3.79)% vs. (31.76±4.65)%, t=-7.81] level was lower than that of the control group ( P<0.01). After treatment, the objective remission rate in the observation group was 7.8% (7/90), and the disease control rate was 87.8% (79/90), while the objective remission rate after treatment in the control group was 5.5% (5/90), and the disease control rate was 82.2% (74/90), and there were no statistical significance in the comparison of objective remission rate and disease control rate of the 2 groups ( χ2=0.09, 0.70, P=0.765, 0.407). The total effective rate after treatment was 62.2% (56/90) in the observation group and 34.4% (31/90) in the control group, and the difference between the 2 groups was statistically significant ( Z=-3.89, P<0.001). WBC [(4.27±1.12)×10 9/L vs. (3.84±1.11)×10 9/L, t=2.58] and haemoglobin [(119.93±17.25)g/L vs. (109.76±15.61)g/L, t=4.15] levels of the observation group were higher than those in the control group after treatment ( P<0.01). During follow-up, the median progression-free survival was 6.2 months in the observation group and 5.5 months in the control group patients, and the difference between the 2 groups was not statistically different ( t=0.11, P>0.05). Conclusion:The combination of Gujin Xiaoji Mixture with warming needle therapy can effectively improve the clinical symptoms of patients with advanced NSCLC with deficiency of qi and yin syndrome, improve the immunity and clinical efficacy of patients, alleviate the adverse effects of drugs, and prolong the progression-free survival period.

Objective To explore the effect of improved total cavity endoscopy on lung function,postoperative feeding and complications in patients with chronic lung disease of esophageal cancer.Methods 120 esophageal cancer patients with chronic lung disease admitted to our hospital from September 2022 to June 2023 were randomly divided into two groups.The observation group consisted of 60 patients who underwent improved total cavity endoscopy assisted esophageal cancer resection,while the control group consisted of 60 patients who underwent traditional open surgery.The perioperative related indexes,lung function indexes[forced expiratory volume in the first second(FEV1),forced vital capacity(FVC),maximum ventilation volume(MVV)],inflammatory level[interleukin-6(IL-6),interleukin-8(IL-8),tumor necrosis factor(TNF-α)]were compared between the two groups.Results The blood loss,operation time,number of lymph node dissection and drainage time in the observation group were(329.51±78.84)ml,(175.47±10.41)min,(29.67±17.86)pieces per case and(3.14±0.98)d respectively.In the control group,the intraoperative blood loss,operation time,number of lymph node dissection and drainage time were(372.31±99.23)ml,(148.54±10.68)min,(28.36±18.15)pieces and(6.37±1.23)d,respectively,there was statistical significance between the two groups(P＜0.05).The FEV,,FVC and MVV of the observation group were(1.88±0.53)L,(2.33±0.46)L and(32.59±11.84)L,respectively.Two weeks after operation,the control group was(1.37±0.31)L,(1.75±0.38)L and(23.68±9.41)L respectively,there was statistical significance between the two groups(P＜0.05).The inflammatory factors IL-6,IL-8 and TNF-α in the observation group were(2.17±1.62)ng/ml,(2.09±1.52)ng/ml and(1.32±0.57)ng/ml,respectively.The control group were(3.06±1.52)ng/ml,(2.75±1.29)ng/ml and(1.73±0.75)ng/ml respectively,there was statistical significance between the two groups(P＜0.05).The incidence of postoperative complications in the observation group and the control group were 6.67％and 20.00％respectively,and patients in the observation group ate earlier than those in the control group(P＜0.05).Conclusion Compared with the traditional open surgery,the improved total laparoscopic surgery has the advantages of less trauma,simpler operation,less damage to lung function,significantly lower incidence of postoperative complications,and shorter postoperative eating time.

Objective:To explore the value of nuclear proliferation index (MIB-1) in the diagnosis and prognosis of adrenal cortical carcinoma (ACC).Methods:A retrospective analysis was conducted on the clinical data of ACC patients and patients with benign adrenal lesions admitted to Beijing Union Medical College Hospital from June 2018 to August 2022. There were 59 cases in the ACC group, 25 males and 34 females, with a male to female ratio of 1∶1.4. Age (46.1 ± 2.1) years old, including 4 cases under 20 years old, 7 cases between 21-30 years old, 11 cases between 31-40 years old, 14 cases between 41-50 years old, 13 cases between 51-60 years old, 8 cases between 61-70 years old, and 2 cases over 70 years old. Body mass index (24.3 ± 2.4) kg/m 2. Systolic blood pressure (149.3 ± 5.2) mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure (93.4±1.7) mmHg. There were 51 cases of typical Cushing's syndrome, 52 cases of hypertension, 44 cases of elevated blood sugar, 16 cases of hypokalemia, and 16 cases of menstrual abnormalities and acne caused by androgen secretion. Laboratory examination: Blood glucose (7.2 ± 0.3) mmol/L, glycated hemoglobin (8.6 ± 1.4)%, total cholesterol (5.7 ± 0.3) mmol/L, and triglycerides (2.0 ± 0.3) mmol/L. 24-hour urine free cortisol (234.4 ± 39.0)μg/24 h, with 46 cases showing an increase, and at 8am, corticotropin releasing hormone (9.5 ± 4.1) pg/ml, with 48 cases showing a decrease. Blood free cortisol (401.2 ± 17.1)μg/dl, with 42 cases of rhythm disappearance. 17 cases showed elevated aldosterone levels. Dehydroepiandrosterone sulfate (713 ± 159)μg/dl, of which 16 cases increased. Neuroenolase (21.2 ± 5.3) ng/ml, of which 27 cases were elevated. Insulin like growth factor-1 was (272.0 ± 42.1) ng/ml, with 26 cases showing an increase. 46 routine high-dose and low-dose dexamethasone inhibition tests were not suppressed. 39 cases of tumors were functional. 59 cases underwent preoperative abdominal and pelvic contrast-enhanced CT, MRI, and B-ultrasound examination, and 21 cases underwent PET/CT examination. The tumors were located in 32 cases on the left, 26 cases on the right, and 1 case on both sides. The maximum diameter of the tumor was (9.6 ± 1.7) cm, with 43 cases ≤10 cm and 16 cases >10 cm. There were 5 cases with lymph node metastasis, 16 cases with distant metastasis, and 11 cases with local invasion. There were 4 cases of tumor ENSAT clinical staging stage Ⅰ(T 1N 0M 0 stage), 27 cases of stage Ⅱ(T 2N 0M 0 stage), 23 cases of stage Ⅲ(T 1-2N 1M 0 stage, T 3N 0M 0 stage), and 5 cases of stage Ⅳ(T 1-4N 0-1M 1 stage, T 3N 1M 0 stage, T 4N 0-1M 0 stage). Six cases were accompanied by tumor thrombi in the central adrenal vein, renal vein, and inferior vena cava. There were 53 cases of benign adrenal tumors, including 26 males and 27 females. Age (44.3±3.2) years old, typical manifestations of Cushing's syndrome in 28 cases, 24-hour urine free cortisol (176.4±41.2) μg/24 h. 27 cases showed disappearance of free cortisol rhythm. Dehydroepiandrosterone sulfate is normal. 23 routine high-dose and low-dose dexamethasone inhibition tests were not inhibited. The maximum diameter of the tumor is (4.2 ± 2.3) cm. T 1N 0M 0 stage patients undergo robotic or laparoscopic radical adrenalectomy, with the resection range including the surrounding lymphoid tissue of the tumor; Patients with stage ≥T 2 underwent open radical adrenalectomy and lymph node dissection. Six cases underwent radical adrenalectomy combined with nephrectomy due to tumor invasion of the kidneys with unclear boundaries. 11 cases of local implant metastasis underwent stereotactic radiotherapy. Nine patients with liver metastasis underwent Interventional Embolization treatment. Three cases with isolated lung metastases underwent surgical resection. Four cases of multiple lung metastases were treated with radiotherapy combined with mitotane. According to the postoperative pathological examination results, record the pathological Weiss score and MIB-1. Analyze the correlation between MIB-1 and clinical pathological indicators and prognosis of patients. Results:There were 59 cases in the ACC group, 35 cases of R0 resection, 19 cases of R1 resection and 5 cases of R2 resection.The postoperative pathological examination showed an average weight of approximately (371±52)g, with 42 cases having a tumor mass ≤ 300 g and 17 cases having a tumor mass>300 g. The positive rate of MIB-1 in the control group was 1% to 5%, while the positive rate of MIB-1 in the ACC group was greater than 5%, the difference between the two groups was statistically significant ( P<0.01). 53 patients diagnosed with capsule invasion, capsule rupture, intravascular tumor thrombus, and MIB-1>10% through postoperative pathological examination were treated with tumor bed radiotherapy and mitotan medication, followed by second-line combination immunotherapy and EDP chemotherapy. The 5-year survival rates of ACC patients with different tumor stages were 65% in stage Ⅰ, 58% in stage Ⅱ, 38% in stage Ⅲ, and less than 5% in stage Ⅳ. The total survival time of the two subgroups with low and high staging was 3.6 years and 1.1 years respectively ( P=0.003), while the disease-free survival time of the two groups was 25 months and 11 months, respectively ( P=0.011). R0 resection has a better prognosis than R1 and R2 resection, and its five-year survival rate is higher ( P=0.03). The 5-year survival rates of R0, R1, and R2 groups were 61%, 31%, and 17%, respectively( P=0.030).Survival analysis showed that adrenal cortical cancer patients with MIB-1 greater than 10% had a worse prognosis, with 5-year OS of 17% and 32% for both groups, respectively ( P=0.021). The Weiss score of the ACC group was (7±2). There were 21 cases in the Weiss score 3-5 group and 38 cases in the 6-9 group, the 5-year survival rates of the two groups were 62% and 19%, respectively ( P=0.017). Conclusions:MIB-1 can serve as an auxiliary diagnostic and prognostic indicator, and high expression of MIB-1 can contribute to the early diagnosis and determination of treatment strategies for ACC.

OBJECTIVES: To investigate the clinical efficacy and safety of salbutamol in the treatment of children with later-onset spinal muscular atrophy (SMA). METHODS: This study is a prospective single-arm phase Ⅲ clinical study. Pediatric patients with SMA type Ⅱ and Ⅲ who visited Department of Neurology, Children's Hospital, Zhejiang University School of Medicine from December 2020 to June 2022 were enrolled. All patients were evaluated with motor function scales, pulmonary function test and drug safety before study. Patients were treated with salbutamol tablets orally, with an initial dose of 1 mg (tid). If tolerable, the dose was increased to 1.5 mg (tid) in the second week, then increased to 2 mg (tid) from the third week and maintained for 6 months. Patients were followed up at 1, 3 and 6 months of treatment. RESULTS: Twenty-six patients were enrolled, including 10 boys and 16 girls. There were 16 cases of SMA type Ⅱ and 10 cases of type Ⅲ with age at treatment initiation of 5.67 (3.13, 7.02) years and disease duration of 2.54 (1.31, 4.71) years. The Hammersmith Functional Motor Scale-Expanded (HFMSE) scores were increased from 14.0 (6.5, 43.0) before treatment to 26.0 (15.0, 46.5) after treatment (Z=－4.144, P<0.01) in 25 cases. The Revised Upper Limb Module Scale scores were increased from 33.0 (25.5, 36.0) before treatment to 35.0 (31.0, 36.5) after treatment (Z=－2.214, P<0.05) in 9 cases. In 7 ambulant children with SMA type Ⅲ, the six minutes walking distance was increased by 30 (15, 52) m after a 6-month treatment (Z=－2.366, P<0.05). Compared with the baseline pulmonary functions the patients showed a significant increase in forced vital capacity (FVC), forced expiratory volume in one second (FEV₁), and peak expiratory flow (PEF) in 15 cases after treatment (all P<0.05). According to patients and caregivers subjective reporting, there were various degrees of improvement in coughing, sputum production ability and exercise endurance. No serious adverse events were observed during the study. CONCLUSIONS Short-term oral administration of salbutamol may improve motor and pulmonary functions in later-onset SMA children with good safety.
Male ; Female ; Humans ; Child ; Albuterol/therapeutic use* ; Prospective Studies ; Muscular Atrophy, Spinal/drug therapy* ; Spinal Muscular Atrophies of Childhood/drug therapy* ; Treatment Outcome

Objective:To evaluate the effect of dexmedetomidine (Dex) on the proliferation, migration and invasion ability of renal carcinoma cells and the relationship with ferroptosis.Methods:Experiment Ⅰ GRC-1 cells at the logarithmic growth phase were selected and divided into 5 groups ( n=6 each) using a random number table method: control group (group C) and different concentrations of dexmedetomidine groups(D1, D2, D3, and D4 groups). Group C was routinely incubated for 24 h. D1, D2, D3, and D4 groups were incubated with dexmedetomidine at 0.1, 1.0, 10.0 and 100.0 μmol/L respectively, for 24 h. The cell proliferation ability was assessed by CCK-8 assay.The cell migration and invasion ability was was evaluated by Transwell chamber assay. Experiment Ⅱ GRC-1 cells at the logarithmic growth phasewere selected and divided into 3 groups ( n=6 each) using a random number table method: control group (group C), dexmedetomidine group (group D), and dexmedetomidine+ Ferrostatin-1 group (group D+ F). Group C was routinely cultured for 24 h. Dexmedetomidine 10 μmol/L was added and cells were incubated for 24 h in group D. Dexmedetomidine 10 μmol/L was added, Ferrostatin-1 1 μmol/L was simultaneously added, and then cells were incubated for 24 h in group D+ F. The proliferation ability of the cells was tested by CCK-8 assay, and the migration and invasion ability of the cells was detected by Transwell assay. The contents of glutathione (GSH), malondialdehyde (MDA) and Fe 2+ were measured by the colorimetric method. The expression of glutathione peroxidase 4(GPX4) and ATF4-induced solute carrier family 7a member 11 (SLC7A11) was detected by Western blot. Results:Experiment I Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased in D3 and D4 groups ( P<0.05), and no significant change was found in aforementioned indexes in D1 and D2 groups ( P>0.05). Experiment Ⅱ Compared with group C, the cell proliferation and the number of migrating and invading cells were significantly decreased, the content of Fe 2+ was increased, the content of GSH was decreased, the expression of GPX4 and SLC7A11 was down-regulated ( P<0.05), and no significant change was found in MDA content in group D( P>0.05). Compared with group D, the cell proliferation and the number of migrating and invading cells were significantly increased, the content of Fe 2+ was decreased, the content of GSH was increased, the expression of GPX4 and SLC7A11 was up-regulated ( P<0.05), and no significant change was found in the MDA content in group D+ F( P>0.05). Conclusions:Dexmedetomidine can inhibit the proliferation, migration and invision ability of renal carcinoma cells, and the mechanism is related to promotion of ferroptosis.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease that affects multiple systems and organs throughout the body. Thrombotic microangiopathy (TMA) is a rare clinical syndrome that can lead to multiple organ dysfunction and even threaten life. Clinically, SLE patients with TMA are relatively rare, especially in children, but the mortality of SLE patients with TMA is significantly increased. The article reports 2 cases of successful remission of SLE complicated with TMA after treatment with eculizumab, and discusses the diagnosis, clinical manifestations and treatment of SLE complicated with TMA in children, so as to provide clinical basis for the diagnosis and treatment of SLE complicated with TMA in children.