ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

OBJECTIVE: To observe the effect of heat-sensitive moxibustion combined with medication on orthostatic hypotension (OH) of yang -qi deficiency in the elderly. METHODS: Sixty elderly patients with OH of yang -qi deficiency were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases). The patients in the control group were treated with oral midodrine hydrochloride tablets, 2.5 mg each time and twice daily, while the patients in the observation group were treated with heat-sensitive moxibustion in addition to the treatment in the control group. Acupoints selected included Dazhui (GV 14), Fengfu (GV 16), and Baihui (GV 20), with each session lasting 30-40 min, once daily. Both groups were treated for 4 weeks. Blood pressure in the supine and standing positions, as well as the decrease of blood pressure when the position changing from supine to standing, were measured before treatment and after 2 and 4 weeks of treatment. Clinical efficacy was also evaluated. RESULTS: After 4 weeks of treatment, both groups showed an increase in systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both the supine and standing positions (P<0.05), and the decrease in SBP and DBP when the position changing from supine to standing was reduced (P<0.05). Compared with the control group, the observation group had higher SBP and DBP in both positions and a smaller decrease in SBP and DBP when the position changing from supine to standing (P<0.05). The total effective rate was 96.6% (28/29) in the observation group, which was higher than 70.0% (21/30) in the control group (P<0.05). CONCLUSION Heat-sensitive moxibustion combined with medication could increase the blood pressure in both supine and standing position, and decrease the reducing of blood pressure when the position changing from supine to standing in elderly patients with OH of yang-qi deficiency.
Humans ; Moxibustion ; Hypotension, Orthostatic/etiology* ; Male ; Aged ; Female ; Combined Modality Therapy ; Acupuncture Points ; Yang Deficiency/therapy* ; Blood Pressure/drug effects* ; Aged, 80 and over ; Middle Aged ; Midodrine

【Objective】 To investigate the risk factors and predictive effectiveness of prostate imaging reporting and data system (PI-RADS) score for patients with clinically significant prostate cancer (CsPCa) whose PI-RADS score was 3, so as to provide evidence for the diagnosis and treatment. 【Methods】 The clinical and multi-parameter magnetic resonance imaging (mpMRI) data of 153 CsPCa patients treated during Jan.2017 and Dec.2021 whose PI-RADS score was 3 were retrospectively analyzed. With PI-RADS score of 3 as the independent risk factor for CsPCa, the other relevant independent risk factors in predicting CsPCa were evaluated. 【Results】 Univariate and multivariate analyses showed that prostate-specific antigen (PSA) density and apparent dispersion coefficient (ADC) were independent risk factors for the diagnosis of CsPCa (P<0.05). Analysis of receiver operating characteristic (ROC) curve showed that combined PSA density and ADC were more effective than PSA density and ADC alone (P<0.05). 【Conclusion】 The combination of PSA density and ADC can guide clinicians to identify high-risk CsPCa patients from patients with PI-RADS score of 3 points.

Objective : To investigate the effects of Lin28 overexpression on the proliferation and osteogenic differentiation of human dental pulp stem cells (hDPSCs) through mTOR signaling pathway. Methods : After transfecting lentiviral vectors of Lin28 gene in hDPSCs , the relative expression of Lin28 was detected by Real⁃time PCR. CCK⁃8 assay was applied to detect the effect on cell proliferation. qRT⁃PCR was used to research the expression levels of alkaline phosphatase (ALP) , osteopontin (OPN) and osteocalcin (OCN) . Western blot assay was processed to investigate the effects on the relative expression levels of ALP and OPN proteins. Alizarin red staining was utilized to detect the mineralized nodules. Results : Compared with the control group , the cell proliferation of transfection group was promoted (P < 0. 05) ; The mRNA and protein expression levels of ALP , OPN and OCN in transfection group were significantly lower than those in control group (P < 0. 05) , the expression level of ALP apparently decreased after the addition of mTOR inhibitor rapamycin (P < 0. 05) ; Alizarin red staining showed that the size and number of mineralized nodules formed in transfection group were markedly declined compared with empty carrier group (P < 0. 05) . Conclusion Overexpression of Lin28 can inhibit the osteogenic differentiation of hDP⁃ SCs through suppress mTOR signaling pathway.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.

Objective:To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease.Methods:In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected.Results:A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and M ( Q1, Q3) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and M ( Q1, Q3) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and M ( Q1, Q3) was 5.72 (2, 7) days.The dose was 40-500 ml, and the M ( Q1, Q3) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Conclusion:Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

Objective:To summarize the clinical characteristics and treatment effect of patients with acute oral 84 disinfectant poisoning, so as to improve the understanding, diagnosis and treatment of the disease.Methods:In January 2022, 25 hospitalized patients with acute oral 84 disinfectant poisoning admitted to our department from March 2016 to August 2021 were selected as the research objects, and their general conditions, poisoning reasons, poisoning time, dose of poisoning, clinical manifestations, blood routine and biochemical indicators, diagnosis, treatment and prognosis were selected.Results:A retrospective analysis was performed. Among the 25 patients, there were 4 males and 21 females, aged from 20 to 91 years, and M ( Q1, Q3) was 38.7 (27, 46) years; The poisoning time (from exposure to poison to treatment) was 1~72 h, and M ( Q1, Q3) was 10.5 (3, 11.5) h. The length of stay was 1~20 days, and M ( Q1, Q3) was 5.72 (2, 7) days.The dose was 40-500 ml, and the M ( Q1, Q3) was 219.6 (100, 330) ml. Chest CT showed exudative changes in both lungs in 4 patients, excessive decreased permeability in 1 case and pleural effusion in 1 case. Gastroscope showed 2 cases of erosive inflammation of gastric body and antrum, 1 case of esophageal ulcer and cardiac ulcer, 1 case of corrosive gastritis, gastric fundus ulcer and esophageal stenosis. Abdominal X-ray showed 1 case of abdominal intestinal dilatation and pneumatosis with multiple gas-liquid planes.There were 1 case of type I respiratory failure, 6 cases of gastrointestinal bleeding and 1 case of incomplete intestinal obstruction. There were 19 cases of nausea and vomiting, 9 cases of abdominal pain, 6 cases of pharyngeal pain and 6 cases of retrosternal burning pain, 1 case of cough and 2 cases of fatigue. Conclusion:Acute oral 84 disinfectant will cause varying degrees of damage to the human digestive tract and lungs. In severe cases, gastrointestinal bleeding, intestinal obstruction, hypoxemia, etc, and even life-threatening, should be paid attention to clinically. The treatment is mainly symptomatic support treatment, such as protecting gastrointestinal mucosa, controlling acute inflammatory reaction, protecting the functions of liver and kidney and other important organs.

[摘 要] 目的：探讨长基因间非编码RNA 00519（long intergene non-coding RNA 00519，LINC00519）调控miR-876-3p/高迁移率家族蛋白A1（high mobility group protein A1，HMGA1）轴在胃癌HGC-27细胞的增殖、凋亡、迁移和侵袭中的作用。方法：采用qPCR检测胃癌细胞HGC-27和胃黏膜上皮细胞GES-1中LINC00519的表达水平。将HGC-27细胞按转染处理分为si-NC、si-LINC00519、si-LINC00519+anti-miR-NC和si-LINC00519+anti-miR-876-3p组，采用集落形成实验检测细胞克隆形成能力，流式细胞术检测细胞凋亡和周期分布，Transwell实验检测细胞迁移和侵袭。双荧光素酶报告实验和qPCR验证LINC00519与miR-876-3p、miR-876-3p与HMGA1之间的相互作用。结果：HGC-27细胞中LINC00519表达较GES-1细胞显著升高（P<0.05），转染siRNA后si-LINC00519组HGC-27细胞中LINC00519的表达水平较si-NC组显著降低（t=47.294，P<0.01）。与si-NC组比较，si-LINC00519组HGC-27细胞克隆数、迁移侵袭数、S期细胞比例均显著降低（均P<0.01），凋亡率、G0/G1期细胞比例均显著升高（均P<0.01）。与si-LINC00519+anti-miR-NC组比较，si-LINC00519+anti-miR-876-3p组HGC-27细胞克隆数、迁移侵袭数、S期细胞比例升高（均P<0.01），凋亡率、G0/G1期细胞比例显著降低（均P<0.01）。LINC00519能够靶向负调控miR-876-3p的表达，miR-876-3p靶向负调控HMGA1的表达。结论：敲降LINC00519能够通过调控miR-876-3p/HMGA1轴抑制胃癌HGC-27细胞的增殖、迁移和侵袭，诱导细胞凋亡。

Objective:To summarize and analyze the clinical data of Chinese patients with colony-stimulating factor 1 receptor (CSF1R)-related leukoencephalopathy, and clarify the phenotypic and genetic characteristics of Chinese patients.Methods:Medical history of patients with CSF1R-related leukoencephalopathy diagnosed from April 1, 2018 to January 31, 2021 in the department of neurology of 22 hospitals in China was collected, and scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment Scale (MoCA), magnetic resonance severity scale were evaluated. Group comparison was performed between male and female patients.Results:A total of 62 patients were included, and the male-female ratio was 1∶1.95. The age of onset was (40.35±8.42) years. Cognitive impairment (82.3%, 51/62) and motor symptoms (77.4%,48/62) were the most common symptoms. The MMSE and MoCA scores were 18.79±7.16 and 13.96±7.23, respectively, and the scores of two scales in male patients (22.06±5.31 and 18.08±5.60) were significantly higher than those in females (15.53±7.41 , t=2.954, P=0.006; 10.15±6.26, t=3.328 , P=0.003). The most common radiographic feature was bilateral asymmetric white matter changes (100.0%), and the magnetic resonance imaging severity scale score was 27.42±11.40, while the white matter lesion score of females (22.94±8.39) was significantly higher than that of males (17.62±8.74 , t=-2.221, P<0.05). A total of 36 CSF1R gene mutations were found in this study, among which c.2381T>C/p.I794T was the hotspot mutation that carried by 17.9% (10/56) of the probands. Conclusions:The core phenotypic characteristics of CSF1R-related leukoencephalopathy in China are progressive motor and cognitive impairment, with bilateral asymmetrical white matter changes. In addition, there exist gender differences clinically, with severer cognitive impairment and imaging changes in female patients. Thirty-six CSF1R gene mutations were found in this study, and c.2381T>C/p. I794T was the hotspot mutation.