The connotation of the "four-dimensional pivot-earth" qi transformation mode is a dialectical system of the ascending and descending of yin-yang qi movement， which presented as "the middle Jiao showing earth qi mediating， the left wheel showing water and wood ascending， and the right wheel showing fire and metal converting and descending". Based on this dialectical thinking， it is believed that the core pathogenesis of myasthenia gravis is deficiency of center qi and transportation failure to pivot-earth； the middle-stage characteristics of the disease progression are the loss of mediation of the central qi， resulting in water coldness and wood constraint， and clear yang failing to ascend； the final outcome of this disease is the loss of astringeing of lung metal and qi sinking. The treatment should be based on the rule of qi movement， so for the start-stage， Buzhong Yiqi Decoction （补中益气汤） should be used as the basis to nourish the earth and consolidate the root， and restrengthen the middle qi； for the middle-stage， herbs like Yingyanghuo （Epimedium brevicornu Maxim.）， Bajitian （Morinda officinalis How） could be combined to warm the water and soothe the wood， raise yang and boost qi； for the final stage， plus Sini Decoction （四逆汤） to astringe metal to stop collapse， and powerfully supplement original qi. All these medicinals can promote pivot-earth re-transportation， four-dimensional transformation， and regular circulation of qi movement， so as to provide thoughts for improving the clinical effectiveness of myasthenia gravis.

OBJECTIVE To evaluate the efficacy and safety of ceftazidime/avibactam （CAZ/AVI） combined with amikacin （AMK） in the treatment of carbapenem-resistant Enterobacteriaceae （CRE） severe pneumonia. METHODS A retrospective cohort study was conducted on 240 patients diagnosed with severe pneumonia caused by CRE infection in the intensive care unit （ICU） of the Affiliated Hospital of Xuzhou Medical University from January 2022 to December 2024. The patients were divided into a combination group （CAZ/AVI combined with AMK， n＝136） and a control group （CAZ/AVI alone， n＝104）. The 28-day mortality rate， clinical efficacy，mechanical ventilation time， ICU stay， infectious markers [C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）， white blood cell count （WBC）， and neutrophil percentage （N%）]， Acute Physiology and Chronic Health Evaluation Ⅱ （APACHE Ⅱ） scores， and total incidence of adverse reactions were compared between two groups of patients. At the same time， subgroup analysis was conducted based on the severity of the condition， mechanical ventilation status， and baseline renal function. RESULTS The 28-day mortality rate of patients in the combination group was significantly lower than that in the control group （20.6% vs. 34.6%， P＝0.022）， and the clinical effective rate was significantly higher than that in the control group （80.1% vs. 65.4%， P＝0.004）. The mechanical ventilation time and ICU hospitalization time in the combination group were significantly shorter than those in the control group （[ 7.2±2.4） days vs. （10.4±3.6） days， （10.5±3.1） days vs. （13.7±3.8） days； P＜0.01].After 7 days of treatment， the CRP， PCT， IL-6， WBC， N% and APACHE Ⅱ scores of patients in the combination group significantly decreased compared to before treatment， and the decrease was significantly greater than that of the control group （P＜0.01）. There was no statistically significant difference in the total incidence of adverse reactions between the two groups of patients （11.8% vs. 13.5%， P＝0.690）. Subgroup analysis showed that among high-risk （APACHE Ⅱ score≥15） and mechanically ventilated patients， the 28-day mortality rate and weaning time of the combination group were significantly lower/ shorter than those of the control group （P＜0.05）， while there was no significant difference in the total incidence of adverse reactions between the combination group and the control group after dose adjustment in patients with chronic renal insufficiency （P＞0.05）. CONCLUSIONS The CAZ/AVI combined with AMK regimen has better anti-infective efficacy and good safety in patients with severe pneumonia caused by CRE infection compared to the CAZ/AVI regimen alone； the survival benefits of this joint regimen are more significant in high-risk and mechanically ventilated patients， with critically ill patients being the main beneficiaries.

In recent years， clinical studies on targeted therapy and immunotherapy for advanced hepatocellular carcinoma used alone or in combination have provided abundant evidence on efficacy and safety for the selection of first-line therapies. However， no consensus has been reached on the selection of second-line therapies in various clinical guidelines for hepatocellular carcinoma， which is caused by the fact that existing evidence is limited to the options after failure of sorafenib and that there is still a lack of high-level evidence for new first-line therapies such as second-line therapies after resistance to targeted therapy and immunotherapy for hepatocellular carcinoma. This article reviews the results of current clinical trials and summarizes the studies on second-line therapies for hepatocellular carcinoma after resistance to first-line targeted therapy and immunotherapy for hepatocellular carcinoma based on the different mechanisms of action of drugs， as well as the research advances in recent years. For hepatocellular carcinoma patients with resistance to first-line targeted therapy and immunotherapy， targeted combination therapy and dual-immune therapy are expected to improve treatment outcome and survival， and more prospective clinical studies are needed in the future to provide effective and safe treatment regimens for hepatocellular carcinoma patients with resistance to targeted therapy and immunotherapy.

Objective To investigate the effect of age on the incidence of cirrhosis and liver cancer in patients with chronic hepatitis B.Methods 279 patients with chronic hepatitis B were divided into the senior group and the younger group according to the age of the patients.The cumulative incidence of cirrhosis and liver cancer during 25 years of follow-up was calculated by using SPSS and R language through the long-term follow-up of HIS system,and the risk factors were analyzed by multivariate logistic regression.Results During follow-up,24 cases developed cirrhosis and 12 cases developed liver cancer.The cumulative incidence of liver cirrhosis was 1.5%,2.1%,5.4%,11.6%and 15.5%in the 5-year,10-year,15-year,20-year and 25-year group,and 5.5%,9.8%,22.9%,29.0%and 52.1%in the elderly,respectively.The difference between the younger age group and senior age group was statistically significant(P<0.001).A total of 2 risk factors(age and follow-up time)were included in the regression model.Two cases in the younger group developed into liver cancer after 17 and 21 years of follow-up,respectively.The cumulative incidence rates at 5,10,15,20 and 25 years were 1.8%,3.8%,18.5%,21.8%and 26.7%.A total of five factors(initial age,HBV-DNA load,HBV-DNA turned negative before the end-point,follow-up time,and sex)were included in the regression model.Conclusions The incidence of cirrhosis and liver cancer in CHB patients aged≥40 years,especially in male patients,is significantly higher than younger CHB patients.Timely initiation of antiviral therapy can delay disease progression and reduce the incidence of termi-nal liver disease.Whether antiviral therapy should be initiated for people aged 30 to 40 years remains to be studied.

To summarize LI Qiangou's clinical experience in treating laryngopharyngeal reflux disease （LPRD） based on the theory of "yang transforming qi while yin constituting form". It is believed that "insufficiency of yang transforming qi and excess of yin constituting form" is the key mechanism of LPRD， in which yang deficiency of the lungs， spleen and kidneys is an important factor causing "insufficiency of yang transforming qi"， while phlegm， dampness and other tangible yin turbidities are the pathological products of "excess of yin constituting form". The key treatment principle is to reinforce yang qi and dispel yin turbidity. Starting from regulating the qi transformation of the sanjiao， the treatment is based on the different pathologies of lung yang insufficiency and phlegm congestion in the upper jiao， spleen yang failing to ascend and dampness accumulation in the middle jiao， and kidney yang deficiency and phlegm-fluid retention in the lower jiao， prescribed by modified Suzi Jiangqi Decoction （苏子降气汤）， Shengyang Chushi Decoction （升阳除湿汤）， and Jingui Shenqi Pill （金匮肾气丸）， the prescriptions could also combine with Banxia Houpo Decoction （半夏厚朴汤） to dissolve phlegm and relieve pharyngeal pains， and regulate qi to direct counterflow downward.

Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.

Hypertension has a high prevalence in China, and the predominant reliance on drug treatment consumes enormous medical resources.Physical exercise is the only widely-accepted nonpharmacologic therapy for hypertension and is potentially cost-effective.How to incorporate exercise into a prescription for rational treatment of hypertension is a topic that needs to be addressed.This review examines the research progress on the treatment of hypertension combining physical exercise with anti-hypertensive drugs in elderly people, aiming to provide some information and options to promote personalized treatment strategies for hypertension in elderly people.

OBJECTIVE To explore the effects of ADRB1 Arg389Gly polymorphisms on the efficacy of bisoprolol， thus providing some information for individualized drug therapy. METHODS A systematic search was conducted in PubMed， Embase， Cochrane Library， CBM， CNKI， and Wanfang Data to retrieve and find out all relevant literature about bisoprolol and ADRB1 Arg389Gly polymorphism from the inception to May 2023. The retrieved literature was screened and selected according to the inclusive and exclusive criteria， thereafter quality assessment was conducted. RevMan 5.4 software was utilized to perform the meta- analysis for the outcome index. RESULTS Overall 7 literature with 1 339 cases were included. Among them， 4 studies provided the changes in systolic blood pressure （SBP）， diastolic blood pressure （DBP） （ΔSBP and ΔDBP）； 4 involving the change （ΔLVEF） of left ventricular ejection fraction （LVEF）. Results of the study showed that there was no statistical significance in the improvement of blood pressure between wild-type group （AA） and mutation group （AG+GG） of ADRB1 Arg389Gly treated with bisoprolol {ΔSBP [SMD＝0.17，95%CI （－0.97，1.31）， P＝0.77]， ΔDBP [SMD＝－0.01，95%CI （－0.65，0.62）， P＝0.97]}； there was no statistical significance in the improvement of ΔLVEF [SMD＝－0.61， 95%CI （－2.74，1.53）， P＝0.58] between 2 groups. CONCLUSIONS ADRB1 Arg389Gly gene polymorphism has no significant influence on the improvement of SBP， DBP， and LVEF in cardiovascular patients who use bisoprolol.

OBJECTIVE To explore the effect of Tuoli Xiaodusan(MDX)on ischemia-reperfusion injury of rat skin flaps and its potential mechanism.METHODS Rats were randomly divided into sham operation group(Sham group),Model group,MDX high-dose group(MDX-H group)and MDX low-dose group(MDX-L group),with 10 rats in each group.After the rat back skin flap model was successfully constructed,the drug was administered by gavage immediately,once a day for 14 consecutive days.The changes of rat skin flaps in each group after surgery were observed,and the survival rate of rat skin flaps in each group was measured on the 14th day after surgery;the histopathological changes of rat skin flaps were observed by HE staining;the protein expression of p-p65 and p-IκBα in the rat skin flap tissue was detected by Western blot;ELISA method was used to detect the expression of TNF-α,IL-1β,and IL-6 cytokines;Ki67 and CD31 immunohistochemical staining were used to observe epidermal basal layer cell prolifera-tion and vascular regeneration.RESULTS Compared with Model group,MDX-H group and MDX-L group had a small amount of e-dema and inflammatory fluid exudation after surgery,and the scab removal time was advanced;the ischemic necrosis of the skin flap was significantly improved,the area of skin flap necrosis was significantly decreased,and the survival rate of rat skin flaps was signifi-cantly increased(P<0.01).In addition,MDX could significantly improve the pathological morphology of ischemia-reperfusion injury in rat back skin flaps,reduce the expression of p-p65 and p-IκBα proteins(P<0.001),and decrease the levels of TNF-α,IL-1β,IL-6 inflammatory factor levels(P<0.05,P<0.01,P<0.001,P<0.000 1).The differences in Ki67 and CD31 also suggested that treatment with MDX accelerate re-epithelialization and blood vessel formation after ischemic flap injury.CONCLUSION MDX plays a role in improving ischemia-reperfusion injury of skin flaps by regulating the NF-κB signaling pathway and accelerating epithelializa-tion and angiogenesis.

Objective:To evaluate the immunogenicity, safety, and immune persistence of the sequential booster with the recombinant protein-based COVID-19 vaccine (CHO cell) in healthy people aged 18-84 years.Methods:An open-label, multi-center trial was conducted in October 2021. The eligible healthy individuals, aged 18-84 years who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, were recruited from Shangyu district of Shaoxing and Kaihua county of Quzhou, Zhejiang province. All participants were divided into three groups based on the differences in prime-boost intervals: Group A (3-4 months), Group B (5-6 months) and Group C (7-9 months), with 320 persons per group. All participants received the recombinant COVID-19 vaccine (CHO cell). Blood samples were collected before the vaccination and after receiving the booster at 14 days, 30 days, and 180 days for analysis of GMTs, antibody positivity rates, and seroconversion rates. All adverse events were collected within one month and serious adverse events were collected within six months. The incidences of adverse reactions were analyzed after the booster.Results:The age of 960 participants was (52.3±11.5) years old, and 47.4% were males (455). The GMTs of Groups B and C were 65.26 (54.51-78.12) and 60.97 (50.61-73.45) at 14 days after the booster, both higher than Group A′s 44.79 (36.94-54.30) ( P value<0.05). The GMTs of Groups B and C were 23.95 (20.18-28.42) and 27.98 (23.45-33.39) at 30 days after the booster, both higher than Group A′s 15.71 (13.24-18.63) ( P value <0.05). At 14 days after the booster, the antibody positivity rates in Groups A, B, and C were 91.69% (276/301), 94.38% (302/320), and 93.95% (295/314), respectively. The seroconversion rates in the three groups were 90.37% (272/301), 93.75% (300/320), and 93.31% (293/314), respectively. There was no significant difference among these rates in the three groups (all P values >0.05). At 30 days after the booster, antibody positivity rates in Groups A, B, and C were 79.60% (238/299), 87.74% (279/318), and 90.48% (285/315), respectively. The seroconversion rates in the three groups were 76.92% (230/299), 85.85% (273/318), and 88.25% (278/315), respectively. There was a significant difference among these rates in the three groups (all P values <0.001). During the sequential booster immunization, the incidence of adverse events in 960 participants was 15.31% (147/960), with rates of about 14.38% (46/320), 17.50% (56/320), and 14.06% (45/320) in Groups A, B, and C, respectively. The incidence of adverse reactions was 8.02% (77/960), with rates of about 7.50% (24/320), 6.88% (22/320), and 9.69% (31/320) in Groups A, B, and C, respectively. No serious adverse events related to the booster were reported. Conclusion:Healthy individuals aged 18-84 years, who had completed primary immunization with the inactivated COVID-19 vaccine 3 to 9 months before, have good immunogenicity and safety profiles following the sequential booster with the recombinant COVID-19 vaccine (CHO cell).