It is the current confusion encountered by integrated Chinese and Western medicine that how to find the breakthrough direction of integrating Chinese and Western medicine， from crossover to integration to innovation， and open up a new horizon of integrated Chinese and Western medicine. The progress of Chinese medicine lay in expanding the scope of diagnosis and treatment with the help of modern diagnostic and therapeutic equipments and developing “micro” identification， while the progress of Western medicine lay in looking at “macro” and developing systemic medicine and integrated medicine， both of which are in the direction of each other. The “state-target identification and treatment” may become an important way to build a modern diagnosis and treatment system of integrated Chinese and Western medicine， and the thinking mode of “from target to state” is a further refinement and development on the basis of the theoretical system of “state-target identification and treatment”， which provided a clearer solution for the current stage of the integrated Chinese and Western medicine model， and pointed out the important development direction for the future integrated Chinese and Western medicine. From the perspective of strategic level and diagnosis and treatment practice， it integrated the “target-state” thinking mode into the modern diagnosis and treatment model of the integrated Chinese and Western medicine， i.e.， “Western medicine as the basis and treating with Chinese medicine； Chinese medicine as the basis and treating with Western medicine”. On the one hand， Western medicine should strengthen the reference to the traditional theories and holism of Chinese medicine， and advocate a higher level of education on the integrated Chinese and Western medicine under the guidance of the traditional theories of Chinese medicine. On the other hand， the “from target to state” mode of thinking should be applied to guide the establishment of diagnostic and treatment strategies and clinical selection of medicines in clinical practice， so as to locate the target and adjust the body state in a gradual and orderly manner， and to provide practical methods for the modern clinical work of the integrated Chinese and Western medicines. Chinese and Western medicine systems can learn from each other， combine organically， give full play to their respective strengths， and form an internal law， so as to make breakthroughs and innovations in the integrated Chinese and Western medicine model.

Objective:To identify the method to reduce X-ray exposure during ablation of atrial fibrillation (AF) by comparing the cryoballoon (CRYO) ablation and remote magnetic navigation (RMN) ablation.Methods:A retrospective analysis was conducted on 144 patients undergoing CRYO ablation (CRYO group) and 121 patients undergoing RMN ablation (RMN group) in our hospital. Entrance surface doses at reference points online, exposure time during procedure and outcomes were analyzed for different types of patients.Results:Compared with the RMN group, the procedure time for the CRYO group significantly decreased [(165.0±23.6), (97.8±18.4) min, t=26.05, P<0.001]. However, the entrance surface dose value [(232.3±130.7), (669.0±387.5) mGy, Z=-12.29, P<0.001] and X-ray exposure time [(8.1±3.1), (23.4±6.2) min, t=-24.57, P<0.001] increased significantly for the CRYO group. No significant difference was found between the two groups in the proportion of maintaining sinus rhythm during follow-up of patients (71.9%, 75.7%, P=0.618). Multiple regression analysis showed that obese patients, patients with non-paroxysmal AF and patients with variant pulmonary veins were associated with an increase in entrance surface dose values in the CRYO group ( t=5.47, 2.23, 3.39, P<0.05). The X-ray exposure time for the three types patients above in the CRYO group also increased ( t=2.87, 3.86, 3.25, P<0.05) in the CRYO group. However, only obese patients in the RMN group had an increase in entrance surface dose value ( Z=-4.15, P<0.001) and no increase in exposure time. For the three types of patients above, there was no significant difference in proportion of maintaining sinus rhythm between the CRYO group and the RMN group during follow-up ( P>0.05). Conclusions:Compared with RMN ablation, the radiation exposure of CRYO AF ablation significantly increased, especially in obese patients, patients with non-paroxysmal AF and patients with pulmonary veins variation. The use of RMN for these types of patients may reduce the radiation exposure without affecting the procedure outcomes.

Objective To investigate the therapeutic effect of Shugan Heluo Xingpi Decoction on CCl 4 -induced liver fibrosis in rats, and the underlying molecular mechanism. Methods Sixty male SPF Wistar rats were randomly assigned to six groups: blank control, model, positive control, high, medium or low dose groups of Shugan Heluo Xingpi Decoction ( n =10 per group). The liver fibrosis rat model was induced by an intraperitoneal injection of 40% CCl 4 oil solution. Rats in the blank control and model groups were administered 10 mL/kg normal saline by gavage, rats in the positive control group were administered 50 mg/kg silibinin meglumine by gavage, while rats in high-dose, medium-dose and low-dose groups of Shugan Heluo Xingpi Decoction were administered 12.42 g/kg, 6.21 g/kg and 3.11 g/kg (crude drug/body weight) by gavage, respectively, daily for 8 weeks. Rats was sacrificed after 8 weeks, during which the physiological status of rats in each group was dynamically monitored. Following sacrifice, serum was collected to detect HYP using alkaline hydrolysis colorimetry and the expression levels of AST, ALT, total protein (TP), and Alb using an automatic biochemical analyzer. The pathological morphological changes in the liver were detected by H & E staining and Masson staining, and the mRNA and protein levels of Wnt1, β-Catenin and Cyclin D1 were detected by RT-qPCR and Western Blot. Measurement data were compared across groups using one-way ANOVA with post-hoc LSD- t test. Results Compared with the model group, after silibinin meglumine and Shugan Heluo Xingpi Decoction intervention, the physiological status of rats was significantly improved; serum levels of HYP, ALT, AST and Glo were significantly decreased, while serum levels of TP, Alb and A/G were significantly increased (all P < 0.05). Compared with the positive control group, serum levels of ALT and AST were significantly increased (all P < 0.05), while the levels of TP, Alb and A/G were significantly decreased (all P < 0.05) in low-dose group of Shugan Heluo Xingpi Decoction. H&E staining showed mild portal vein fibrosis with a few fibrous septa and mild steatosis of hepatocytes in the positive control group, obvious portal vein fibrosis with a few fiber septum in the low dose group, a few portal vein fibrosis in the medium dose group, while no obvious abnormality in the high dose group of Shugan Heluo Xingpi Decoction. Masson staining revealed that the therapeutic effect of high dose group of Shugan Heluo Xingpi Decoction on collagen deposition was superior to silibinin meglumine and medium and low dose of Shugan Heluo Xingpi Decoction (all P < 0.05), and was generally equivalent to high dose of Shugan Heluo Xingpi Decoction. Silibinin meglumine and medium and high doses of Shugan Heluo Xingpi Decoction inhibited more significantly the mRNA and protein expression of Wnt1, β-catenin and Cyclin D1 (all P < 0.05). Conclusion Shugan Heluo Xingpi Decoction shows anti-hepatic fibrosis effect, with a greater effect at higher doses. Regulating Wnt/β-Catenin signaling pathway may be one of the underlying molecular mechanisms.

Targeted gene therapy has become a promising approach for lung cancer treatment. In our previous work, we reported that the targeted expression of microRNA-7 (miR-7) operated by thyroid transcription factor-1 (TTF-1) promoter inhibited the growth of human lung cancer cells in vitro and in vivo; however, the intervention efficiency needed to be further improved. In this study, we identified the core promoter of TTF-1 (from -1299 bp to -871 bp) by 5' deletion assay and screened out the putative transcription factors nuclear factor-1 (NF-1) and activator protein-1 (AP-1). Further analysis revealed that the expression level of NF-1, but not AP-1, was positively connected with the activation of TTF-1 core promoter in human non-small-cell lung cancer (NSCLC) cells. Moreover, the silencing of NF-1 could reduce the expression level of miR-7 operated by TTF-1 core promoter. Of note, we optimized four distinct sequences to form additional NF-1-binding sites (TGGCA) in the sequence of TTF-1 core promoter (termed as ^optTTF-1 promoter), and verified the binding efficiency of NF-1 on the ^optTTF-1 promoter by electrophoretic mobility shift assay (EMSA). As expected, the ^optTTF-1 promoter could more effectively drive miR-7 expression and inhibit the growth of human NSCLC cells in vitro, accompanied by a reduced transduction of NADH dehydrogenase (ubiquinone) 1α subcomplex 4 (NDUFA4)/protein kinase B (Akt) pathway. Consistently, ^optTTF-1 promoter-driven miR-7 expression could also effectively abrogate the growth and metastasis of tumor cells in a murine xenograft model of human NSCLC. Finally, no significant changes were detected in the biological indicators or the histology of some important tissues and organs, including heart, liver, and spleen. On the whole, our study revealed that the optimized TTF-1 promoter could more effectively operate miR-7 to influence the growth of human NSCLC cells, providing a new basis for the development of microRNA-based targeting gene therapy against clinical lung cancer.
Animals ; Humans ; Mice ; Carcinoma, Non-Small-Cell Lung/therapy* ; Lung Neoplasms/metabolism* ; MicroRNAs/metabolism* ; Nuclear Proteins/metabolism* ; Thyroid Gland/pathology* ; Thyroid Nuclear Factor 1/genetics* ; Transcription Factors/metabolism*

  Objective  To study the demographic and clinical characteristics, correlation of genotype and phenotype and treatment of Blau syndrome to facilitate early diagnosis and timely treatment of Blau syndrome.  Methods  Seventy-two patients with Blau syndrome from 11 centers from May 2006 to April 2022 were retrospectively analyzed, and their general information, clinical data, laboratory examination and treatment medication were collected.  Results  The distribution of patients with Blau syndrome was uniform in geographical north and south of China, and there was no obvious gender bias. The mean age of onset was (14.30±12.81) months, and the age of diagnosis was (55.18±36.22) months. 35% of patients with Blau syndrome happened before 1 year old, and all patients developed before 5 years old. 87.50% (63/72) had granulomatous arthritis, 65.28% (47/72) had rash, 36.11% (26/72) had ocular involvement, 27.78% (20/72) had fever, and 15.28% (11/72) had pulmonary involvement. Arthritic manifestations of Blau syndrome were most at risk, followed by rash, ocular involvement, and fever.The first 25 months of the disease, the risk of developing a rash was the greatest. The risk of developing arthritis was the greatest between 25 months and 84 months. The main mutations were p.R334Q and p.R334W, and patients with p.R334Q mutation had relatively high incidence of fever (35.71%[5/14] vs. 14.29%[1/7], P=0.43) and ocular involvement (42.86%[6/14]vs. 28.57%[2/7], P=0.51). There was a relatively high incidence of rash (85.71%[6/7] vs. 64.29%[9/14], P=0.59) in patients with the p.R334W mutation. Forty-five patients(62.50%)were treated with a combina-tion of glucocorticoid and methotrexate. Twenty-two patients were treated with tumor necrosis factor antagonist in addition to glucocorticoid and methotrexate.  Conclusions  The risk of different clinical manifestations of Blau syndrome from high to low was arthritis, followed by rash, ocular involvement and fever. The main treatment was glucocorticoid combined with methotrexate, to which biological agents could be added.

Objective To investigate the effect and its molecular mechanism of phosphoglycerate mutase 5 (PGAM5) mediated pyroptosis on liver ischemia-reperfusion injury (IRI). Methods C57 mouse models of liver IRI were established and randomly divided into the 6 h reperfusion (6 h group) and 12 h reperfusion (12 h group), and sham operation group (sham group) was established too, 10 rats in each group. The effect of IRI on the parameters in the liver tissues and serum samples was evaluated. The expression levels of PGAM5 and cysteinyl aspartate specific proteinase (Caspase)-1 in the liver tissues during IRI were quantitatively detected. The IRI models of liver cells were established (IRI group). The IRI models of liver cells were established after pretreatment with Caspase-1 inhibitor Z-YVAD-FMK (inhibitor group). The untreated AML12 cells were allocated into the control group. The effect of inhibiting Caspase-1 activity on pyroptosis was analyzed. AML12 cells were transfected with PGAM5 small interfering ribonucleic acid (siRNA) (siRNA group) and siRNA-negative control (siRNA-NC) (siRNA-NC group) by liposome 3000, and then IRI models of liver cells were established. The untreated AML12 cells were assigned into the control group. The effect of PGAM5 mediated pyroptosis on IRI of liver cells was assessed. Results In the 6 h and 12 h groups, partial liver cell edema, hepatic sinusoid narrowing, central vein congestion and occasional spot necrosis were observed in the mouse liver tissues, and these changes in the 12 h group were more aggravated than those in the 6 h group. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the 6 h and 12 h groups were higher than those in the sham group, and the values in the 12 h group were higher than those in the 6 h group. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were increased in the 6 h and 12 h groups, and the values in the 12 h group were lower than those in the 6 h group. The relative expression levels of IL-1β messenger ribonucleic acid (mRNA) in the mouse liver tissues in the 6 h and 12 h groups were up-regulated, and the value in the 12 h group was lower than that in the 6 h group. The cell apoptosis rates in the liver tissues were significantly increased in the 6 h and 12 h groups, and the value in the 12 h group was remarkably lower than that in the 6 h group (P < 0.01-0.05). Compared with the sham group, the relative expression levels of PGAM5 mRNA and protein in the mouse liver tissues in the 6 h and 12 h groups were significantly up-regulated, and the values in the 12 h group were significantly higher than those in the 6 h group (P < 0.01-0.05). The protein expression levels of PGAM5 and Caspase-1 in the liver tissues were up-regulated in the 6 h and 12 h groups. Compared with the control group, the relative expression levels of NOD-like receptor protein 3 (NLRP3), cleaved Caspase-1 and Gasdermin D (GSDMD) proteins were up-regulated and the fluorescence intensity of GSDMD was increased in the IRI group. Compared with the IRI group, the relative expression levels of NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated and the fluorescence intensity of GSDMD was considerably decreased in the inhibitor group (P < 0.01-0.05). Compared with the control group, the cell survival rate was significantly decreased, and the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly up-regulated in the siRNA-NC group (P < 0.01-0.05). Compared with the siRNA-NC group, the cell survival rate was remarkably increased, whereas the relative expression levels of PGAM5, NLRP3, cleaved Caspase-1 and GSDMD proteins were significantly down-regulated in the siRNA group (P < 0.01-0.05). Conclusions PGAM5 may aggravate the liver IRI in mouse models probably by mediating pyroptosis via PGAM5/Caspase-1/GSDMD signaling pathway and aggravating liver cell injury.

Objective:To describe the COVID-19 epidemic and its characteristics in Heilongjiang province, and provide evidence for the further prevention and control of COVID-19 in the province.Methods:The information of COVID-19 cases and clusters were collected from national notifiable disease report system and management information system for reporting public health emergencies of China CDC. The Software’s of Excel 2010 and SPSS 23.0 were applied for data cleaning and statistical analysis on the population, time and area distributions of COVID-19 cases.Results:On January 22, 2020, the first confirmed case of COVID-19 was reported in Heilongjiang. By March 11, 2020, a total of 482 cases domestic case of COVID-19, The incidence rate was 1.28/100 000, the mortality rate was 2.70% (13/482) in 13 municipalities in Heilongjiang. There were 81 clusters of COVID-19, The number of confirmed cases accounted for 79.25% (382/482) of the total confirmed cases and 12 cases of deaths. The family clusters accounted for 86.42% (70/81). Compared with the sporadic cases, the mortality rate, proportion of elderly cases aged 60 or above and severe or critical cases of clinical classification were all higher in the clusters especially the family clusters, but the differences were not significant ( P>0.05). There were 34 clusters involving more than 5 confirmed cases accounted for 41.98% (34/81) of the total clusters, the involved cases accounted for 68.31% (261/382) of the total cases of clusters. There were significant differences in age distribution of the cases among the case clusters with different case numbers. In the clusters involving 6-9 cases, the proportion of cases aged 65 years or above was more (26.53%, 39/147). Conclusions:The incidence rate of COVID-19 was relatively high and the early epidemic was serious in Heilongjiang, The number of cases was large in clusters especially family clusters.

Objective:To optimize the formulation of HA-CA liposomes and to study the anti-tumor effect of HA-CA liposomes on uterine cervical carcinoma mice.Methods:The methods of preparing HA-CA liposomes were screened,and the optimal fomulation was selected by the orthogonal design experiment with the the phospholipids/cholesterol ratio,the drug/lipids ratio and the pH value of PBS buffer was 7.4 as entrapment enfficiency was the index.The release of HA-CA liposomes was studyed by dialysis bag method.Uterine cervical carcinoma cells were inoculated subcutaneously into right axillary ofBal b/c mice,after continuous treatment of 14 d,we weighed the tumor and calculated the rate of tumor growth inhibition.Results:HA-CA liposomes were prepared by thin film hydration methods.The optimal parameters were as follows:the phospholipids/cholesterol ratio was 4∶1,the drug/lipids ratio was 1∶ 30,the pH value of PBS buffer was 7.4.The release curve of HA-CA liposome and CA liposome was basically the same,both of which a sustained-release efficacy.The cumulative release of HA-CA liposomes and CA liposomes were 78.39％ and 83.01％ at 48h.The inhibition rate of HA-CA liposomes on U14 cervical cancer mice was 60.39％ and significantly higher than that of positive control group,which was higher than that of CA and CA liposomes.Conclusions:HA-CA liposomes can significantly inhibit the effect of U14 cervical cancer nude mice higher than that of CA and CA liposomes owe to the modification of the active target ligand HA.

Objective To observe the analgesic effect of acupuncture at Guanyuan (CV4) and its effect on vasomotor substances in rats with dysmenorrhea due to coagulated cold syndrome. Method The coagulated-cold dysmenorrhea rat model was developed by Estrodiol benzoate and Oxytocin injectin plus physical freezing. The writhing response (writhing latency, writhing frequency, and writhing score) was observed, and the contents of TXB2 and 6-keto-PGF1a were detected by using enzyme-linked immunosorbent assay (ELISA). Result Compared with the saline water group, the writhing latency was significantly shortened, the writhing frequency was significantly increased, and the writhing score was more significantly increased in the model group (P<0.01);compared with the model group, the writhing latency was significantly prolonged, the writhing frequency was decreased, and the writhing score was significantly lower in the acupuncture group (P<0.05, P<0.01). Compared with saline water group, the content of plasma 6-keto-PGF1a was significantly lower (P<0.05) and the content of plasma TXB2 showed an increasing tendency (P>0.05) in the model group. Compared with the model group, the content of plasma 6-keto-PGF1a showed an increasing tendency (P>0.05) and the content of plasma TXB2 showed a decreasing tendency (P>0.05) in the acupuncture group. Conclusion The vasomotor substances are obviously disordered in the blood of cold-coagulated dysmenorrhea rat models. Acupuncture at Guanyuan can improve the writhing response and release pain, and meanwhile positively regulate the vasomotor substances such as TXB2 and 6-keto-PGF1a. The vasomotor substances are plausibly one of the major substances in the action of acupuncture in preventing and treating dysmenorrhea.

Objective To explore the effect of different acupuncture stimuli on uterine micro-circulation of dysmenorrheal rats with cold stagnation syndrome. Methods Totally 32 three-month old female SD rats in diestrus were randomly divided into saline control group, model group, A stimuli group, and B stimuli group, 8 rats in each group. Model group and treatment groups were given whole body freezing combined with estradiol benzoate injection method to establish models. A stimuli group was given deep puncture with manipulation, while B stimuli group was treated by shallow puncture without manipulation. Diameter of uterine capillary,micro-vessel, TXB2, and 6-keto-PGF1αlevels were observed in each group. Results Compared with the saline group, capillary diameter in model group was significantly reduced at 5, 10, 20, 30 min time point (P<0.01);micro-vascular diameter was significantly reduced at 5, 10, 20, 30, 40 min time point (P<0.01);plasma 6-keto-PGF1α levels decreased (P<0.01);TXB2/6-keto-PGF1αincreased significantly (P<0.01). Compared with model group, capillary diameter in A stimuli group enlarged at 5, 10, 20, 30 min time point (P<0.05), micro-vascular diameter dilated at 5, 10, 20, 30, 40 min time point (P <0.01), plasma 6-keto-PGF1α level increased (P <0.05), TXB2/6-keto-PGF1αdecreased significantly (P<0.05);micro-vascular diameter in B stimuli group dilated at 20, 30 min time point (P<0.05), plasma TXB2/6-keto-PGF1α decreased significantly (P<0.05). Compared with B stimuli group, capillary diameter in A stimuli group dilated at 5, 10, 20, 30 min time point (P<0.05) and micro-vascular diameter dilated at 5, 10, 20, 30, 40 min time point significantly (P<0.01). Conclusion Dysmenorrheal rats with cold stagnation syndrome show obvious disorder of the uterus micro-circulation and circulation related substances. Both A and B acupuncture stimuli improved uterus micro-circulation of dysmenorrheal rats with cold stagnation syndrome, and its mechanism may be related to the recovery the balance between TXB2 and 6-keto-PGF1α.