Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q exactive focus mass spectrometry, network pharmacology, and molecular docking.

OBJECTIVE: To elucidate the chemical profile and the pharmacological mechanism by which Jinlingzi powder (, JLZP) treats bile reflux gastritis (BRG). METHODS: A BRG model was established in rats by oral administration of the model solution. JLZP was orally administered for 35 d. Residual gastric rate and tumor necrosis factor (TNF)-α, interleukin (IL)-6, and gastrin levels in the serum were measured, and stomach tissues were collected for histopathological analysis. We used ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry to identify the chemical ingredients in JLZP. Then, protein-protein interaction and herb-compound-target networks were constructed to screen potential bioactive compounds and targets. Kyoto Encyclopedia of Genes and Genomes pathway analysis was then performed to elucidate the pathway involved in the JLZP-mediated treatment of BRG. After constructing the core compound-target-pathway interaction network, molecular docking was performed to study the binding free energy of core bioactive compounds and two candidate targets [RAC-alpha serine/threonine-protein kinase (AKT1) and phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform (PIK3CA)]. RESULTS: JLZP extracts significantly promoted gastric emptying, regulating the release of cytokines (TNF-α and IL-6) and improving gastrin secretion and mucosal repair. Fifty-six compounds were tentatively characterized in JLZP. Moreover, the network pharmacology and molecular docking results showed that alkaloids and flavonoids might be the bioactive compounds in JLZP that treat BRG. JLZP might improve mucosal repair during BRG progression by modulating the phosphatidylinositol-4,5-bisphosphate 3-kinase-protein kinase B, hypoxia inducible factor-1, mitogen-activated protein kinase, forkhead box O, TNF, and IL-17 signaling pathways. CONCLUSIONS: We elucidated the chemical constituents and the pharmacological mechanism of JLZP in treating BRG and provided a basis for clinical application.

Bloodletting puncture in the treatment of acute ischemic stroke: protocol for a mixed-method study of a multi-center randomized controlled trial and focus group.

This study is to investigate the effectiveness and safety of bloodletting puncture (BP) for acute ischemic stroke (AIS) when used in combination with standard treatment, as well as the patients' feelings and attitudes toward the treatment. This is a mixed method research which includes a multi-center, superiority, randomized controlled clinical trial, and focus group interview. A total of 360 AIS participants will be enrolled. They will be randomized into one of the following two groups for 7 d: (a) BP with standard treatment group (n = 180); (b) standard treatment group (n = 180). The primary outcome will be National Institute of Health stroke scale (NIHSS) score at day 7 after treatment. Secondary outcomes will be changes of Glasgow Coma Scale score, NIHSS score, mRS and Traditional Chinese Medicine syndrome score from baseline to 7, 14, and 30 d after treatment, recurrence rate and all-cause mortality rate within 30 d, and the safety assessments. The focus group will be conducted with a purposive sample of 1-2 acupuncturists and 1-2 patients respectively at each center at 7 and 30 d after treatment. We designed a mixed method study to evaluate the effect of BP, an acupuncture therapy for patients with AIS. If the findings of this study confirm the effectiveness of BP to reduce the NIHSS score and other related outcomes and patients are willing to accept the therapy, we believe this study will help the implementation of this therapy in clinical practice, and provide new evidence for the treatment of AIS.

[The efficacy of radiotherapy based combined therapy for unresectable locally invasive bladder cancer and its associated factors analysis].

Objective: Retrospective analysis of the efficacy and influencing factors of bladder preservation integrated therapy for unresectable invasive bladder cancer confined to the pelvis was done, also including the bladder function preservation and adverse effects analysis. Methods: Sixty-nine patients with unresectable locally invasive bladder cancer who received radiotherapy-based combination therapy from March 1999 to December 2021 at our hospital were selected. Among them, 42 patients received concurrent chemoradiotherapy, 32 underwent neoadjuvant chemotherapyand 43 with transurethral resection of bladder tumors (TURBT) prior to radiotherapy. The late adverse effect of radiotherapy, preservation of bladder function, replase and metastasis and survival were followed-up. Cox proportional hazards models were applied for the multifactorial analysis. Results: The median age was 69 years. There were 63 cases (91.3%) of uroepithelial carcinoma, 64 of stage Ⅲ and 4 of stage Ⅳ. The median duration of follow-up was 76 months. There were 7 grade 2 late genito urinary toxicities, 2 grade 2 gastrointestinal toxicities, no grade 3 or higher adverse events occurred. All patients maintained normal bladder function, except for 8 cases who lost bladder function due to uncontrolled tumor in the bladder. Seventeen cases recurred locally. There were 11 cases in the concurrent chemoradiotherapy group with a local recurrence rate of 26.2% (11/42) and 6 cases in the non-concurrent chemoradiotherapy group with a local recurrence rate of 22.2% (6/27), and the difference in local recurrence rate between the two groups was not statistically significant (P=0.709). There were 23 cases of distant metastasis (including 2 cases of local recurrence with distant metastasis), including 10 cases in the concurrent chemoradiotherapy group with a distant metastasis rate of 23.8% (10/42) and 13 cases in the non-concurrent chemoradiotherapy group with a distant metastasis rate of 48.1% (13/27), and the distant metastasis rate in the non-concurrent chemoradiotherapy group was higher than that in the concurrent chemoradiotherapy group (P=0.036). The median 5-year overall survival (OS) time was 59 months and the OS rate was 47.8%. The 5-year progression-free survival (PFS) time was 20 months and the PFS rate was 34.4%. The 5-year OS rates of concurrent and non-concurrent chemoradiotherapy group were 62.9% and 27.6% (P<0.001), and 5-year PFS rates were 45.4% and 20.0%, respectively (P=0.022). The 5-year OS rates of with or without neoadjuvant chemotherapy were 78.4% and 30.1% (P=0.002), and the 5-year PFS rates were 49.1% and 25.1% (P=0.087), respectively. The 5-year OS rates with or without TURBT before radiotherapy were 45.5% and 51.9% (P=0.233) and the 5-year PFS rates were 30.8% and 39.9% (P=0.198), respectively. Multivariate Cox regression analysis results showed that the clinical stage (HR=0.422, 95% CI: 0.205-0.869) was independent prognostic factor for PFS of invasive bladder cancer. The multivariate analysis showed that clinical stages (HR=0.278, 95% CI: 0.114-0.678), concurrent chemoradiotherapy (HR=0.391, 95% CI: 0.165-0.930), neoadjuvant chemotherapy (HR=0.188, 95% CI: 0.058-0.611), and recurrences (HR=10.855, 95% CI: 3.655-32.638) were independent prognostic factors for OS of invasive bladder cancer. Conclusion: Unresectable localized invasive bladder cancer can achieve satisfactory long-term outcomes with bladder-preserving combination therapy based on radiotherapy, most patients can retain normal bladder function with acceptable late adverse effects and improved survival particularly evident in patients with early, concurrent chemoradiotherapy and neoadjuvant chemotherapy.

Consensus on diagnostic criteria for deficiency syndrome in hypertension: a modified Delphi study.

OBJECTIVE: To reach consensus on the diagnostic criteria for deficiency syndrome in hypertension (YDSH) patients by a modified Delphi method. METHODS: Our study was consistent with T/CACM 1032-2017. The methodology of RAND/UCLA appr-opriateness was used to develop consensus guidance statements. A nationwide panel of experienced clinical experts from 19 provinces was constructed. These experts were all prominent in Traditional Chinese Medicine (TCM) of cardiovascular diseases. This con-sensus process consisted of two rounds of ques-tionnaires and a final round of consultation to analyze the weight score of each item. Moreover, the data extraction process is carried out independently by third-party researchers (LIANG Junya, SUN Yang, and DU Xiaona). When there is disagreement in all three rounds, the expert panel group (odd number) are invited to vote, and the one with more votes wins. In the questionnaires, participants were asked to rate the appropriateness of each syndrome item using a nine-point Likert scale. The consensus was defined as a panel median rating 1-3 or 7-9 without disagreement. And then the diagnostic criteria of YDSH were formed according to the weight score in the final round. RESULTS: Twenty-eight experts (84.8%) participated in the first round, and thirty-one (93.9%) finished the second round. After two rounds, the consensus of YDSH was reached on 11 items (25.6%), including symptoms, signs, and pulse condition. Twenty-one experts (63.6%) com-pleted the final round in which they used a grading system for each item. Red tongue with scanty fur had the highest weighting (22.8%), followed by heat in the palms and soles (20.1%). CONCLUSIONS: The consensus-based diagnostic criteria for YDSH, formed by a modified Delphi method, can be widely incorporated in TCM. A further clinical study will be conducted to analyze the diagnosis value and cut-off score of our YDSH criteria.

Shugan Jieyu capsule improve sleep and emotional disorder in coronavirus disease 2019 convalescence patients: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the efficacy of the Shugan Jieyu capsule on improving sleep and emotional disorder during Coronavirus disease 2019 (COVID-19) convalescence. METHODS: We conducted a randomized, double-blind, placebo-controlled trial, and recruit 200 COVID-19 convalescence patients and then divide the subjects into two groups respectively: the experimental group ( 100) and the control group ( 100). Patients in the control group were given doses as a placebo, while those in the experimental group were given Shugan Jieyu capsule. The investigators mainly observed the differences between the two groups before and after treatment in terms of the rate of reduction and the rate of efficiency in Hamilton Depression Scale (HAMD-17) total scores from baseline, and recorded the scores of Hamilton Anxiety Scale (HAMA), Patient Health Questionnaire-15 (PHQ-15), Insomnia Severity Index (ISI) and Treatment Emergent Symptom Scale at 2 week, the 4 week and the 6 week respectively after treatment, and compared the differences between the groups. And the occurrence of adverse events was recorded. RESULTS: After 6-week treatment, there were statistically significant differences in the rate of reduction as well as efficiency in HAMD-17 scores, HAMA Total Scores, PHQ-15 Score, ISI Score from baseline in the experimental group and control group (< 0.05). There were 4 adverse events in the experimental group and 1 in the control group. CONCLUSION: Shugan Jieyu capsule could significantly improve sleep and emotional disorder in patients during COVID-19 convalescence.

[Analysis of clinical characteristics, treatment and survival of elderly patients with large diffuse B-cell lymphoma].

Objective: To analyze the clinical feature,treatment and survival outcome of elderly patients older than 80 years with large diffuse B-cell lymphoma. Methods: A total of 46 patients aged over 80 years with large diffuse B-cell lymphoma who were treated in Third Hospital of Peking University during the period from 2002 to 2018 were retrospectively analyzed, and the clinical features, laboratory data, survival and prognostic factors were included in Kaplan-Meier and prognostic analysis. Results: Patients older than 80 years old accounted for 15.7% (46/293) in all elderly patients, and the median age was 83 years old. There were 78.3% (36/46)patients who belonged to stage Ⅲ or Ⅳ, 63%(29/46) who had more than two extranodal organ involvement, and the higher proliferation index(Ki-67≥80%) was present in 53.7%(22/41) patients. Immunohistochemistry showed that 37% patients in 27 cases were double-expressed DLBCL. With a median follow-up of 25 months, the overall response rate (ORR) for the whole group was 63.0%, the complete response (CR) rate was 36.4%, the 2, 3-year progression-free survival (PFS) rate was 49.9% and 41.7%, the 2, 3-year overall survival (OS) rate was 54.6% and 43.6% respectively. The ORR for patients who received anthracycline-based therapies and non-anthracycline-based therapies were 81.8% and 55.0%, and the 3-year OS rate were 50.0% and 39.0%, respectively, but the difference was not statistically significant (P>0.05). 45.5% patients had hematologic toxicity of Grade Ⅲ or above, and 56.8% patients experienced infections during the treatment. Among the patients who died, the treatment-related mortality rate in group with high score of Charlson comorbidity index(CCI) was higher (43.8% vs 16.7%, P=0.03) . The National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) score, nodal involvement area ≥3, 6 cycles of chemotherapy, CCI score, initial treatment outcome and refractory-relapsed were predictive of overall survival. Multivariate analysis indicated the CCI score (HR=6.463, P=0.008) and initial treatment outcome (HR=0.086, P=0.001) were independent prognostic risk factors. Conclusions: The clinical and pathological features of patients older than 80 years were highly aggressive with poor chemotherapy tolerance and high adverse reaction rate. Anthracycline-based therapies may be less important in the treatment of DLBCL patients aged over 80 years. Patients with high CCI score have higher treatment-related mortality and CCI can help identify elderly patients who are suitable for larger chemotherapy dose.

Integrative Palliative Cancer Care in Hong Kong: An Overview and an Example from the East.

Cancer is the most common cause of mortality worldwide. Although recent advances of multiple modality cancer management have significantly improved the cure and control rates, a significant proportion of patients are still refractory to the standard and available treatments. Early initiation of palliative care can reduce cancer suffering, improve health-related quality of life and possibly prolong survival. It also allows patients and their caretakers to perceive the trajectory of their cancer, so that better and advanced care planning can be contemplated and implemented. The traditional beliefs and perceptions of cancer also differ significantly between the East and the West, which may also affect the preferential approach to palliative care. This review provides an overview of palliative care services in Hong Kong, as compared with other parts of the world. In addition, we shall also explore how cancer perceptions affect the decision-making on palliative care.

Growth of injected melanoma cells is suppressed by whole body exposure to specific spatial-temporal configurations of weak intensity magnetic fields.

PURPOSE: To measure the effect of exposure to a specific spatial-temporal, hysiologically-patterned electromagnetic field presented using different geometric configurations on the growth of experimental tumours in mice. METHODS: C57b male mice were inoculated subcutaneously with B16-BL6 melanoma cells in two blocks of experiments separated by six months (to control for the effects of geomagnetic field). The mice were exposed to the same time-varying electromagnetic field nightly for 3 h in one of six spatial configurations or two control conditions and tumour growth assessed. RESULTS: Mice exposed to the field that was rotated through the three spatial dimensions and through all three planes every 2 sec did not grow tumours after 38 days. However, the mice in the sham-field and reference controls showed massive tumours after 38 days. Tumour growth was also affected by the intensity of the field, with mice exposed to a weak intensity field (1-5 nT) forming smaller tumours than mice exposed to sham or stronger, high intensity (2-5 microT) fields. Immunochemistry of tumours from those mice exposed to the different intensity fields suggested that alterations in leukocyte infiltration or vascularisation could contribute to the differences in tumour growth. CONCLUSIONS: Exposure to specific spatial-temporal regulated electromagnetic field configurations had potent effects on the growth of experimental tumours in mice.

Consumption of medium- and long-chain triacylglycerols decreases body fat and blood triglyceride in Chinese hypertriglyceridemic subjects.

OBJECTIVES: To investigate the effects of medium- and long-chain triacylglycerol (MLCT) on blood triglyceride (TG) in Chinese hypertriglyceridemic subjects. METHODS: A double-blind controlled clinical trial was carried out, in which 112 subjects with hypertriglyceridemia were randomly divided into two dietary oil groups: (1) long-chain triacylglycerol (LCT) and (2) MLCT. All subjects were requested to ingest fixed energy and to continue their normal activity levels, and to consume LCT or MLCT oil at 25-30 g daily during the study period. Anthropometric measurements of body weight, body mass index (BMI), body fat, body fat percentage, waist and hip circumference (WC and HC), areas of subcutaneous and visceral fat by computed tomography scanning and blood biochemical markers were measured at the beginning and end of the study. RESULTS: There were 50 and 51 subjects left in LCT and MLCT groups, respectively. There were no significant differences in daily intake of energy, protein, fat and carbohydrate, as well as the daily physical activity between the two groups during the study. After 8 weeks, MLCT group showed a significant decrease in body weight, BMI, WC, HC, ratio of WC and HC, body fat, body fat percentage and subcutaneous fat when compared with the initial values. The decrease in body weight, BMI, WC, body fat and subcutaneous and visceral fat was significantly greater in MLCT group than that in the LCT group. Furthermore, the serum concentrations of TG in MLCT group were significantly lower than those in the LCT group. CONCLUSIONS: Consumption of MLCT may reduce body weight, body fat and blood TG in hypertriglyceridemic subjects under an appropriate dietary regime.

[Effects of glutamate and glutamine on learning and memory of rats].

The effects of glutamate (Glu) and glutamine (Gln) on learning and memory of rats and the mechanism involved were examined. Three groups of rats were fed with stock diet (control group), and the diets supplemented with 2% Glu (Glu group) or 2% Gln (Gln group) respectively. Compared with control group, the active avoidance response rats of Gln group in shuttle box test was significantly elevated while the time of passive avoidance response shortened. The contents of brain free amino acids, such as Gln, Glu, aspartic acid and arginine, activity of brain nitric oxide synthase (NOS), Bmax of N-methyl-D-aspartate(NMDA) receptors in hippocampus of Gln group were all increased significantly. Such changes were not observed in Glu group. The results suggested that Gln could improve the learning ability and memory of rats, which might be related to the change of amino acids composition of brain, the synthesis of messenger nitric oxide and the binding capacity of NMDA receptor in hippocampus.

[Chemical constituents of the roots of Bupleurum longicaule Wall. ex DC. var. franchetii de Boiss and B. chaishoui Shan et Sheh].

From the roots of Bupleurum longicaule var. franchetii, B. chaishoui and the official species B. chinense, ten saikosaponins have been isolated and identified as saikosaponin a, saikosaponin d, saikosaponin c, saikosaponin e, saikosaponin b2, 2"-O-acetylsaikosaponin a, 3"-O-acetylsaikosaponin a, 3"-O-acetylsaikosaponin d, 6"-O-acetylsaikosaponin a and 6"-O-acetylsaikosaponin d respectively. It has been shown that the chemical constituents of these three Bupleurum plants are very similar, therefore, the medicinal value of B. longicaule var. franchetii and B. chaishoui is further verified.

[Treatment of congestive heart failure complicating chronic Keshen disease with magnesium sulfate and captopril].

150 hospital patients of chronic Keshen disease with congestive heart failure were divided into two groups: the treatment group (TG) and control group (CG). Patients in TG (80 patients) were treated with magnesium sulfate and captopril, while those in CG (70 patients) with digoxin. The results showed a marked difference (P < 0.01) in the total effective ratio between TG (92.5 percent) and CG (65.7 percent). Both groups had an increase in cardiac output and cardiac index, but it was more apparent in TG. With sum vessel resistance (SVR), TG had a remarkable decrease (P < 0.01), patients in while those in CG did not (P > 0.05). The results also showed that the therapeutic effect in TG was satisfactory. The important function of magnesium, the basis of its treatment and the simultaneous administration of magnesium and captopril to reduce the cardiac preload and afterload and to improve the heart function were discussed.