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 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.

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: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.

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.

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 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).

Familial adenomatous polyposis and Lynch syndrome represent two different molecular pathways of colorectal carcinogenesis that are commonly considered mutually exclusive: chromosomal instability and microsatellite instability. Here, we report a rare case of familial adenomatous polyposis in an adult male with Lynch-like syndrome. A 46-year-old male patient was found to have hundreds of adenomatous polyps throughout the whole intestine, and irregular masses in rectum, sigmoid and transverse colon. Genetic test showed that the patient carried pathogenic germline APC (c.423-1G>A) variant and two variants of uncertain significance in MLH1 (p.R725H) and PTCH1 (p.S438N), combined with tumor characteristics of somatic AKT1/PIK3CA/KRAS co-mutations, microsatellite instability and high tumor mutation burden. The patient underwent laparoscopic total colectomy with abdominoperineal resection and end ileostomy, then received 4 cycles adjuvant chemotherapy of oxaliplatin with capecitabine. This patient was followed up to April 2024 and performed well without abnormalities in serum cancer biomarkers and radiological examinations.

Objective:To observe the clinical effect of lower eyelid blepharoplasty combined with micro-autologous fat transplantation (MAFT) in the rejuvenation of the infraorbital regions.Method:A retrospective analysis was conducted on the clinical data of patients with lower eyelid pouch and tear trough treated with lower eyelid blepharoplasty combined with MAFT in the Department of Plastic Surgery of Affiliated Hospital of Nanjing University of Chinese Medicine from March 2020 to March 2022. Patients seeked medical attention due to lower eyelid pouch and tear trough, with or without skin laxity, and some patients had varying degrees of midface depression. After preoperative examination and evaluation of the patient’s infraorbital area and midfacial depression, appropriate individualized plans were developed.The patient underwent lower eyelid blepharoplasty by transconjunctival approach combined with tear trough MAFT. For patients with low or depressed midface, midface MAFT was also performed, and for patients with skin laxity, skin removal surgery was performed simultaneously. Complications were recorded after the operation. Preoperative and postoperative photos of more than 6 months were taken with the same postion and delivered to the same doctor to grade the patient’s Barton classification (0-3 grades, with higher grade indicating more obvious tear trough deformity). The improvement of tear trough deformity after surgery was assessed, and the global aesthetic improvement scale (GAIS) score was also assessed. The patients evaluated their improvement using the patients aesthetic improvement scale (PAIS) score (GAIS and PAIS are both 1-5 points, with higher scores indicating more significant postoperative improvement). Normal distribution metric data was represented by Mean±SD, and count data was represented by frequency and/or percentage; skewed distribution metric data was represented by M ( Q1, Q3), and compared by rank sum test. Results:A total of 69 patients were enrolled, including 9 males and 60 females, aged 25-45 years, with an average age of 36.7 years. Among them, 35 patients had midfacial depression, and 11 patients had skin laxity. (0.37±0.07) ml (0.2-0.6 ml) of micro-autologous fat was injected into the orbicularis oculi muscle on each side; (0.18±0.06) ml (0.1-0.2 ml) of micro-autologous fat was injected into the subcutaneous layer on each side; (3.80±0.98) ml (3-5 ml) of micro-autologous fat was injected into the deep medial cheek fat compartment and pyriform aperture fat compartment on each side. No serious complications occurred after the surgery. Postoperative follow-up lasted for 6-13 months, with an average of 8.7 months. The patient’s lower eyelid pouch, tear trough deformity, and depression in the midface have all improved, presenting a youthful and smooth appearance from the infraorbital area to the midface. The skin texture in the lower eyelid area had also improved. At the last follow-up, the Barton classification of the lacrimal groove decreased compared with that before surgery, and the difference was statistically significant [grade 0 (0, 1) vs. grade 2 (1, 2), Z=-7.62, P<0.001]. At the last follow-up, the PAIS score of 69 patients was 5 points in 49 cases (71%) and 4 points in 20 cases (29%); doctor’s GAIS score was 5 points in 38 cases (55%), 4 points in 27 cases (39%), and 3 points in 4 cases (6%) . Conclusion:For those patients with aging status of infraorbital region, like lower eyelid pouch and tear trough deformities, the combination of lower eyelid blepharoplasty through the transconjunctival approach and MAFT can achieve good therapeutic effects. This method is safe with a short recovery time.

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.