Humans ; Aged ; Lung Diseases ; Pneumonia/drug therapy* ; Adrenal Cortex Hormones/therapeutic use* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Administration, Inhalation ; Community-Acquired Infections/drug therapy*

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Osteoporosis leads to an imbalance in bone remodelling, where bone resorption is greater than bone formation and osteoclast degradation increases, resulting in severe bone loss. Autophagy is a lysosomal degradation pathway that regulates the proliferation, differentiation, and apoptosis of various bone cells (including osteoblasts, osteoclasts, and osteoclasts), and is deeply involved in the bone remodelling process. In recent years, the role of autophagy in the progression of osteoporosis and related bone metabolic diseases has received more and more attention, and it has become a research hotspot in this field. Summarising the existing studies, it is found that senile osteoporosis is the result of a combination of factors. On the one hand, it is the imbalance of bone remodelling and the increase of bone resorption/bone formation ratio with ageing, which causes progressive bone loss. On the other hand, aging leads to a general decrease in the level of autophagy, a decrease in the activity of osteoblasts and osteoclasts, and an inhibition of osteogenic differentiation. The lack of oestrogen leads to the immune system being in a low activation state, and the antioxidant capacity is weakened and inflammatory response is increased, inducing autophagy-related proteins to participate in the transmission of inflammatory signals, excessive accumulation of reactive oxygen species (ROS) in the skeleton, and negatively regulating bone formation. In addition, with aging and the occurrence of related diseases, glucocorticoid treatments also mediate autophagy in bone tissue cells, contributing to the decline in bone strength. Exercise, as an effective means of combating osteoporosis, improves bone biomechanical properties and increases bone density. It has been found that exercise induces oxidative stress, energy imbalance, protein defolding and increased intracellular calcium ions in the organism, which in turn activates autophagy. In bone, exercise of different intensities activates messengers such as ROS, PI3K, and AMP. These messengers signal downstream cascades, which in turn induce autophagy to restore dynamic homeostasis in vivo. During exercise, increased production of AMP, PI3K, and ROS activate their downstream effectors, AMPK, Akt, and p38MAPK, respectively, and these molecules in turn lead to activation of the autophagy pathway. Activation of AMPK inhibits mTOR activity and phosphorylates ULK1 at different sites, inducing autophagy. AMPK and p38 up-regulate per-PGC-1α activity and activate transcription factors in the nucleus, resulting in increased autophagy and lysosomal genes. Together, they activate FoxOs, whose transcriptional activity controls cellular processes including autophagy and can act on autophagy key proteins, while FoxOs proteins are expressed in osteoblasts. Exercise also regulates the expression of mTORC1, FoxO1, and PGC-1 through the PI3K/Akt signalling pathway, which ultimately plays a role in the differentiation and proliferation of osteoblasts and regulates bone metabolism. In addition, BMPs signaling pathway and long chain non-coding RNAs also play a role in the proliferation and differentiation of osteoblasts and autophagy process under exercise stimulation. Therefore, exercise may become a new molecular regulatory mechanism to improve osteoporosis through the bone autophagy pathway, but the specific mechanism needs to be further investigated. How exercise affects bone autophagy and thus prevents and treats bone-related diseases will become a future research hotspot in the fields of biology, sports medicine and sports science, and it is believed that future studies will further reveal its mechanism and provide new theoretical basis and ideas.

Objective To observe the pharmacokinetic effect of amoxicillin and clavulanate potassium tablets on amoxicillin in Chinese healthy subjects under fasting and high fat and high calorie diet.Methods 71 healthy subjects were given a single dose of amoxicillin potassium clavulanate tablets(0.375 g)on fasting or high fat diet,and venous blood samples were collected at different time points.The concentrations of amoxicillin in human plasma were determined by HPLC-MS/MS method,and the pharmacokinetic parameters were calculated by non-atrioventricular model using PhoenixWinNonlin 8.0 software.Results The main pharmacokinetic parameters of amoxicillin potassium clavulanate tablets after fasting and high fat diet were(5 105.00±1 444.00),(4 593.00±1 327.00)ng·mL-1,and postprandial-fasting ratio 89.40％,90％confidence interval(79.55％-100.19％);t1/2 were(1.52±0.16),(1.39±0.22)h;AUC0-t were(12 969.00±1 841.00),(11 577.00±1 663.00)ng·mL-1·h,and postdietary/fasting ratio 89.20％,90％confidence interval(83.92％-94.28％);AUC0-∞ were(13 024.00±1 846.00),(11 532.00±1 545.00)ng·mL-1·h,and postprandial-fasting ratio 88.60％,90％confidence interval(83.48％-93.50％).The median Tmax(range)were 1.63(0.75,3.00)and 2.50(0.75,6.00)h,respectively,and the Tmax of postprandial medication was delayed(P＜0.01).Conclusion Compared with fasting condition,amoxicillin Tmax was significantly delayed after high fat diet,while Cmax,AUC0-t and AUC0-∞ were not significantly changed,indicating that food could delay the absorption of amoxicillin,but did not affect the degree of absorption.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Objective To observe the efficacy and safety of Morinda officinalis oligosaccharides in the continuation treatment of mild and moderate depression.Methods An open,single-arm,multi-center design was adopted in our study.Adult patients with mild and moderate depression who had received acute treatment of Morinda officinalis oligosaccharides were enrolled and continue to receive Morinda officinalis oligosaccharides capsules for 24 weeks,the dose remained unchanged during continuation treatment.The remission rate,recurrence rate,recurrence time,and the change from baseline to endpoint of Hamilton Depression Scale(HAMD),Hamilton Anxiety Scale(HAMA),Clinical Global Impression-Severity(CGI-S)and Arizona Sexual Experience Scale(ASEX)were evaluated.The incidence of treatment-related adverse events was reported.Results The scores of HAMD-17 at baseline and after treatment were 6.60±1.87 and 5.85±4.18,scores of HAMA were 6.36±3.02 and 4.93±3.09,scores of CGI-S were 1.49±0.56 and 1.29±0.81,scores of ASEX were 15.92±4.72 and 15.57±5.26,with significant difference(P＜0.05).After continuation treatment,the remission rate was 54.59％(202 cases/370 cases),and the recurrence rate was 6.49％(24 cases/370 cases),the recurrence time was(64.67±42.47)days.The incidence of treatment-related adverse events was 15.35％(64 cases/417 cases).Conclusion Morinda officinalis oligosaccharides capsules can be effectively used for the continuation treatment of mild and moderate depression,and are well tolerated and safe.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.

ObjectiveTo evaluate the therapeutic effect of stewed Polygoni Multiflori Radix on androgenic alopecia （AGA） and study the treatment mechanism. MethodNinety-nine SPF-grade male C57BL/6J mice were randomized into control， model， positive drug （finasteride， 0.65 mg·kg^-1）， low （0.78 g·kg^-1）， medium （1.56 g·kg^-1）， and high （3.12 g·kg^-1）-dose stewed Polygoni Multiflori Radix， and Polygoni Multiflori Radix Praeparata groups by the random number table method. The mouse model of AGA was constructed by subcutaneous multi-point injection of testosterone propionate diluent for 60 days， and the mice were administrated with corresponding drugs by gavage from day 11. The therapeutic effects of stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata on AGA were evaluated by newly hair area， hair length， hair weight in the hair removal area， and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was employed to determine the levels of testosterone （T）， dihydrotestosterone （DHT）， and 5α-reductase （5-AR） in the skin tissue of mice. Western blot was employed to determine the expression levels of key proteins in the Wnt/β-catenin signaling pathway. ResultCompared with the control group， the model group （after 60 days of modeling） showed reductions in the newly hair area， hair length and weight in the back hair removal area， and ratio of hair follicles containing melanin to total hair follicles （P<0.05， P<0.01）， elevated levels of T， DHT， and 5-AR， up-regulated expression level of glycogen synthase kinase-3β （GSK-3β） （P<0.05， P<0.01）， and down-regulated expression levels of β-catenin， phospho-glycogen synthase kinase-3β （p-GSK-3β）， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue. Compared with the model group， the positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low-， medium-， and high-dose Polygoni Multiflori Radix Praeparata improved the newly hair area and hair length of mice （P<0.01）， and stewed Polygoni Multiflori Radix and Polygoni Multiflori Radix Praeparata at low and medium doses improved the weight of newly formed hair in mice （P<0.05， P<0.01）. The positive drug， low-， medium-， and high-dose stewed Polygoni Multiflori Radix， and low- and high-dose Polygoni Multiflori Radix Praeparata increased the ratio of hair follicles containing melanin to total hair follicles in the skin tissue （P<0.05， P<0.01）. Compared with Polygoni Multiflori Radix Praeparata at the same doses， the medium and high doses of stewed Polygoni Multiflori Radix increased the ratio of melanin-containing hair follicles to total hair follicles （P<0.05）. Compared with the model group， stewed Polygoni Multiflori Radix lowered the levels of T and DHT， down-regulated the expression level of GSK-3β （P<0.01）， and up-regulated the expression levels of β-catenin， p-GSK-3β， and p-GSK-3β/GSK-3β （P<0.05， P<0.01） in the skin tissue of the mice. ConclusionStewed Polygoni Multiflori Radix can ameliorate androgenic alopecia in mice by reducing the androgen level and promoting Wnt/β-catenin signaling.

Pharmaceutical cocrystals is an advanced technology to improve the physicochemical and biological properties of drugs. However, there are few studies on the in vivo metabolism of pharmaceutical cocrystals. In this study, the pharmacokinetics of wogonin cocrystal in normal rats was further studied on the basis of the previous preparation of wogonin-aloperine cocrystal. Firstly, an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was established for simultaneous determination of wogonin and its metabolite wogonoside in rat plasma, and to investigate the methodology. The method was applied to the pharmacokinetic study of wogonin-aloperine cocrystal (Wog-Alop) in rats. The results showed that wogonin and its metabolite wogonoside had a good linear relationship in the range of 1-800 ng·mL^-1, and the precision, accuracy, matrix effect and stability in this range met the requirements of biological analysis. Compared with direct administration of wogonin, the C_max of wogonin and its metabolite in rats increased to 7.44-fold and 9.15-fold, AUC_0-t increased to 1.67-fold and 3.72-fold, and oral bioavailability of wogonin increased to 187.66% after cocrystal administration. Wog-Alop cocrystal can significantly improve the C_max, AUC, and oral bioavailability of wogonin and its metabolite, which provides a new perspective for the clinical application of wogonin. This study was approved by the Experimental Animal Ethics Review Committee of Beijing University of Chinese Medicine (approval number: BUCM-2023032307-1148).