Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Artificial intelligence(AI)has demonstrated great potential in the diagnosis and treatment of pancreatic cancer.It plays an important role in medical imaging analysis,pathological slide recognition,drug efficacy and prognosis prediction,as well as new drug development by leveraging deep learning algorithms.Despite challenges such as data acquisition and model interpretability,advancements in technology and data sharing are expected to further enhance its role in early screening,personalized treatment,and innovative drug discovery for pancreatic cancer,ultimately improving patient outcomes.

Objective:To investigate the effects of anisodamine hydrobromide (654-1), 654-1+ norepinephrine and norepinephrine on early hemodynamic indexes of piglets with septic shock.Methods:A total of 38 healthy Bama pigs were selected as the study subjects, 32 of which were treated with lipopolysaccharide to create septic shock piglet model, and the other 6 were sham operation group. The animals were randomly divided into control group ( n=8), drug treatment group [654-1 group ( n=8), 654-1+ norepinephrine group ( n=8), norepinephrine group ( n=8)]. Hemodynamic parameters were recorded at T 0 (basic state), T 1 (successful shock modeling), T 2 (1 h after successful modeling), T 3 (2 h after successful modeling), T 4 (4 h after successful modeling), T 5 (6 h after successful modeling) and T 6 (8 h after successful modeling) respectively, including: Mean arterial pressure (MAP), cardiac index (CI), whole-heart end-diastolic volume index (GEDI), lactic acid (LAC). Results:Except for the sham operation group, MAP of all treatment groups at T 1 was significantly lower than that at T 0 (all P<0.05). MAP of all treatment groups at T 2-T 6 was significantly higher than that at T 1 (all P<0.05). T 1 MAP of all treatment groups was significantly lower than that of the sham operation group (all P<0.05). MAP at T 2-T 6 in the norepinephrine group and the 654-1+ norepinephrine group was higher than that in the control group (all P<0.05), and MAP at T 2-T 4 in the 654-1 group was significantly lower than that in the 654-1+ norepinephrine group (all P<0.05). LAC of all treatment groups at T 1-T 3 was significantly higher than that at T 0 (all P<0.05) except the sham operation group. LAC in the group 654-1 at T 4 to T 6 was significantly lower than that at T 1 (all P<0.05). LAC in the group 654-1 at T 4-T 6 was significantly lower than that in the norepinephrine group and the control group (all P<0.05). The CI of norepinephrine group at T 2, T 5 and T 6 was lower than that at T 0 (all P<0.05). There was no significant difference in CI between T 2 and T 6 compared with T 1 (all P>0.05). CI of the 654-1+ norepinephrine group at T 4 was significantly lower than that of T 0 ( P<0.05); The CI of the 654-1 group at T 2 was significantly higher than that of T 1 ( P<0.05). CI at T 1 in the 654-1+ norepinephrine group was significantly lower than that in the sham operation group (all P<0.05). The GEDI at T 1 to T 5 in the 654-1 group was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), and the GEDI at T 1 to T 2 was significantly lower than that at T 0 in the 6541+ norepinephrine group (all P<0.05), while the GEDI at T 2 and T 4 was higher than that at T 1 (all P<0.05). Conclusions:MAP decreased significantly in septic shock, LAC increased significantly in the early stage of shock. 654-1 can improve MAP in early stage of septic shock, and significantly reduce LAC level in early stage of septic shock.

Objective To investigate the effects of Fuzheng Touxie Prescription on pulmonary injury of Pseudomonas aeruginosa pneumonia(PAP)in rats;To discuss its possible mechanism.Methods A total of 36 SD rats were divided into blank group,model group,piperacillin group and Fuzheng Touxie Prescription low-,medium-and high-dosage groups according to random number table method,with 6 rats in each group.Except for the blank group,0.1 mL of Pseudomonas aeruginosa suspension with a concentration of 3×109 CFU/mL was injected through oral catheterization.In the blank group,0.1 mL sterile saline was injected by oral catheterization.Fuzheng Touxie Prescription low-,medium-and high-dosage groups were gavaged 1.6 mL of Fuzheng Touxie Prescription solution with the concentration of 0.43,0.86 and 1.73 g/mL respectively,the blank group and model group were gavaged equal volume of distilled water,piperacillin group was intraperitoneal injected 0.53 mL piperacillin tazobactam sodium solution with a concentration of 0.11 g/mL,once a day,for consecutive 3 days.HE staining was used to observe the pathological changes of lung tissue,lung injury score was performed and bronchial wall thickness was measured,flow cytometry was used to detect Th17/Treg ratio in peripheral blood,the serum contents of RORγt,FoxP3,TGF-β and inflammatory factors TNF-α,IL-6 and IL-10 were detected by ELISA,the mRNA expression of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by RT-qPCR,the protein expressions of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by Western blot.Results Compared with the blank group,a large amount of inflammatory cell infiltration was observed in lung tissue of the model group rats,accompanied by bronchial wall hyperplasia,alveolar dilation,interstitial edema,and a significant increase in lung injury score and bronchial wall thickness(P<0.01),the proportion of Th17 in peripheral blood increased(P<0.01),the proportion of Treg decreased(P<0.01),and the Th17/Treg ratio increased(P<0.05),the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly increased(P<0.01),the contents of FoxP3 and IL-10 significantly decreased(P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly increased(P<0.01),while the mRNA and protein expressions of FoxP3 and IL-10 significantly decreased(P<0.01).Compared with the model group,the alveoli of rats in each treatment group were relatively intact and the structure was clearer,inflammatory cell infiltration,pulmonary interstitial edema and congestion were reduced,and lung injury scores and bronchial wall thickness were reduced(P<0.05,P<0.01),the proportion of Th17 in peripheral blood decreased(P<0.05),the proportion of Treg increased(P<0.05),and the Th17/Treg ratio decreased(P<0.05)in Fuzheng Touxie Prescription high-dosage group and piperacillin group,the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly decreased in Fuzheng Touxie Prescription medium-and high-dosage groups and piperacillin group(P<0.05,P<0.01),the contents of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly decreased(P<0.05,P<0.01),the mRNA and protein expressions of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01).Conclusion Fuzheng Touxie Prescription can improve pulmonary inflammatory symptoms,reduce the level of inflammatory factors and increase the level of anti-inflammatory factors in PAP rats.The mechanism may be through the TGF-β/RORγt/FoxP3 pathway to regulate immune balance.

OBJECTIVE To explore the risk factors for serum COVID-19 antibodies in the population of Fuzhou to provide scientific basis for prevention and control strategies.METHODS The prospective study and the multi-stage stratified random sampling method were performed to select at least 200 subjects from each of the 12 counties(cit-ies)in Fuzhou.Questionnaires follow-ups and serum collections were conducted in Mar,Jun,Sep,and Dec.2024,respectively.The antibody levels in Dec.were divided into a high protective antibody group(IgG antibody≥50 AU/ml)and a low protective antibody group(IgG antibody≤20 AU/ml).The influencing factors of serum anti-body levels were analyzed by multivariate logistic regression model.RESULTS A total of 2816 subjects were en-rolled.In Mar,1454 subjects with high-protective antibodies were identified.After nine months of follow-up,of the 1454 subjects,344 had high protective antibodies and 369 had low protective antibodies in Dec..There were statistically significant differences in age,presence of typical symptoms after infection,underlying diseases,surgi-cal history,healing time,smoking and drinking histories between the high and low antibody groups(P<0.05).Multivariate logistic regression model showed that older age,underlying diseases,history of surgery,smoking and drinking were risk factors which could reduce antibody levels(P<0.05),while typical symptoms after infec-tion and longer recovery time were protective factors which could increase antibody levels(P<0.05).After the COVID-19 infection in spring of 2024,the serum antibody levels in Fuzhou residents showed the downward trend,especially after Sep.2024,with a more pronounced downward trend.CONCLUSIONS According to the risk factors of COVID-19 antibody levels,prevention and control efforts should be focused on the key population.It is necessa-ry to strengthen health education and carry out vaccination to maintain the levels of immunity to protect population from COVID-19 infection.

Objective To investigate the effects of Fuzheng Touxie Prescription on pulmonary injury of Pseudomonas aeruginosa pneumonia(PAP)in rats;To discuss its possible mechanism.Methods A total of 36 SD rats were divided into blank group,model group,piperacillin group and Fuzheng Touxie Prescription low-,medium-and high-dosage groups according to random number table method,with 6 rats in each group.Except for the blank group,0.1 mL of Pseudomonas aeruginosa suspension with a concentration of 3×109 CFU/mL was injected through oral catheterization.In the blank group,0.1 mL sterile saline was injected by oral catheterization.Fuzheng Touxie Prescription low-,medium-and high-dosage groups were gavaged 1.6 mL of Fuzheng Touxie Prescription solution with the concentration of 0.43,0.86 and 1.73 g/mL respectively,the blank group and model group were gavaged equal volume of distilled water,piperacillin group was intraperitoneal injected 0.53 mL piperacillin tazobactam sodium solution with a concentration of 0.11 g/mL,once a day,for consecutive 3 days.HE staining was used to observe the pathological changes of lung tissue,lung injury score was performed and bronchial wall thickness was measured,flow cytometry was used to detect Th17/Treg ratio in peripheral blood,the serum contents of RORγt,FoxP3,TGF-β and inflammatory factors TNF-α,IL-6 and IL-10 were detected by ELISA,the mRNA expression of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by RT-qPCR,the protein expressions of RORγt,FoxP3 and inflammatory factors in lung tissue were detected by Western blot.Results Compared with the blank group,a large amount of inflammatory cell infiltration was observed in lung tissue of the model group rats,accompanied by bronchial wall hyperplasia,alveolar dilation,interstitial edema,and a significant increase in lung injury score and bronchial wall thickness(P<0.01),the proportion of Th17 in peripheral blood increased(P<0.01),the proportion of Treg decreased(P<0.01),and the Th17/Treg ratio increased(P<0.05),the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly increased(P<0.01),the contents of FoxP3 and IL-10 significantly decreased(P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly increased(P<0.01),while the mRNA and protein expressions of FoxP3 and IL-10 significantly decreased(P<0.01).Compared with the model group,the alveoli of rats in each treatment group were relatively intact and the structure was clearer,inflammatory cell infiltration,pulmonary interstitial edema and congestion were reduced,and lung injury scores and bronchial wall thickness were reduced(P<0.05,P<0.01),the proportion of Th17 in peripheral blood decreased(P<0.05),the proportion of Treg increased(P<0.05),and the Th17/Treg ratio decreased(P<0.05)in Fuzheng Touxie Prescription high-dosage group and piperacillin group,the contents of serum RORγt,TNF-α,TGF-β and IL-6 significantly decreased in Fuzheng Touxie Prescription medium-and high-dosage groups and piperacillin group(P<0.05,P<0.01),the contents of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01),the mRNA and protein expressions of RORγt,TNF-α,TGF-β and IL-6 in lung tissue significantly decreased(P<0.05,P<0.01),the mRNA and protein expressions of FoxP3 and IL-10 significantly increased(P<0.05,P<0.01).Conclusion Fuzheng Touxie Prescription can improve pulmonary inflammatory symptoms,reduce the level of inflammatory factors and increase the level of anti-inflammatory factors in PAP rats.The mechanism may be through the TGF-β/RORγt/FoxP3 pathway to regulate immune balance.

Artificial intelligence(AI)has demonstrated great potential in the diagnosis and treatment of pancreatic cancer.It plays an important role in medical imaging analysis,pathological slide recognition,drug efficacy and prognosis prediction,as well as new drug development by leveraging deep learning algorithms.Despite challenges such as data acquisition and model interpretability,advancements in technology and data sharing are expected to further enhance its role in early screening,personalized treatment,and innovative drug discovery for pancreatic cancer,ultimately improving patient outcomes.

OBJECTIVE To explore the risk factors for serum COVID-19 antibodies in the population of Fuzhou to provide scientific basis for prevention and control strategies.METHODS The prospective study and the multi-stage stratified random sampling method were performed to select at least 200 subjects from each of the 12 counties(cit-ies)in Fuzhou.Questionnaires follow-ups and serum collections were conducted in Mar,Jun,Sep,and Dec.2024,respectively.The antibody levels in Dec.were divided into a high protective antibody group(IgG antibody≥50 AU/ml)and a low protective antibody group(IgG antibody≤20 AU/ml).The influencing factors of serum anti-body levels were analyzed by multivariate logistic regression model.RESULTS A total of 2816 subjects were en-rolled.In Mar,1454 subjects with high-protective antibodies were identified.After nine months of follow-up,of the 1454 subjects,344 had high protective antibodies and 369 had low protective antibodies in Dec..There were statistically significant differences in age,presence of typical symptoms after infection,underlying diseases,surgi-cal history,healing time,smoking and drinking histories between the high and low antibody groups(P<0.05).Multivariate logistic regression model showed that older age,underlying diseases,history of surgery,smoking and drinking were risk factors which could reduce antibody levels(P<0.05),while typical symptoms after infec-tion and longer recovery time were protective factors which could increase antibody levels(P<0.05).After the COVID-19 infection in spring of 2024,the serum antibody levels in Fuzhou residents showed the downward trend,especially after Sep.2024,with a more pronounced downward trend.CONCLUSIONS According to the risk factors of COVID-19 antibody levels,prevention and control efforts should be focused on the key population.It is necessa-ry to strengthen health education and carry out vaccination to maintain the levels of immunity to protect population from COVID-19 infection.

ObjectiveTo develop traditional Chinese medicine （TCM） formulae for the treatment of nonsevere coronavirus disease 2019 （COVID-19） and to explore its anti-inflammatory mechanism. MethodsThe dysregulated signaling pathways were determined in macrophages from bronchoalveolar lavage fluid of COVID-19 patients and in lung epithelial cells infected with SARS-CoV-2 in vitro based on transcriptome analysis. A total of 102 TCM formulae for the clinical treatment of nonsevere COVID-19 were collected through literature. The pathway-reversing rates of these formulae in macrophages and lung epithelial cells were evaluated based on signature signaling pathways， and the basic formula was determined in conjunction with TCM theory. The commonly used Chinese materia medica for nonsevere COVID-19 were summarized from the 102 TCM formulae as abovementioned. And together with the screening results from the Pharmacopoeia of the People's Republic of China， a “Chinese materia medica pool” was esta-blished for the development of TCM formulae for COVID-19. The regulatory effects of each herb on signaling pathways were obtained based on targeted transcriptome analysis. Oriented at reversing dysregulated signaling pathways of COVID-19， the calculation was carried out， and the artificial intelligent methods for compositing formulae， that are exhaustive method and parallel computing， were used to obtain candidate compound formulas. Finally， with reference to professional experience， an innovative formula for the treatment of nonsevere COVID-19 was developed. The ethanol extract of the formula was evaluated for its anti-inflammatory effects by detecting the mRNA expression of interleukin 1b （Il1b）， C-X-C motif chemokine ligand 2 （Cxcl2）， C-X-C motif chemokine ligand 10 （Cxcl10）， C-C motif chemokine ligand 2 （Ccl2）， nitric oxide synthase 2 （Nos2）， and prostaglandin-endoperoxide synthase 2 （Ptgs2） using reverse transcription-quantitative polymerase chain reaction （RT-qPCR） in RAW264.7 cells treated with lipopolysaccharide （LPS）. ResultsIn macrophages and lung epithelial cells， 34 dysregulated signaling pathways associated with COVID-19 were identified respectively. The effects of the 102 formulae for clinical treatment of nonsevere COVID-19 were evaluated based on the dysregulated signaling pathways and targeted transcriptome， and the result showed that Yinqiao Powder and Pingwei Powder （银翘散合平胃散， YQPWP） ranked first， reversing 91.18% of the dysregulated signaling pathways in macrophages and 100% of the dysregulated signaling pathways in lung epithelial cells. Additionally， YQPWP had the function of scattering wind and clearing heat， resolving toxins and removing dampness in accordance with the pathogenesis of wind-heat with dampness in COVID-19. It was selected as the basic formula， and was further modified and optimized to develop an innovative fomula Qiaobang Zhupi Yin （翘蒡术皮饮， QBZPY） based on expert experience and artificial intelligence in composing formulae. QBZPY can reverse all the dysregulated signaling pathways associated with COVID-19 in macrophages and lung epithelial cells， with the reversing rates of 100%. The chief medicinal of QBZPY， including Lianqiao （Fructus Forsythiae）， Xixiancao （Herba Siegesbeckiae） and Niubangzi （Fructus Arctii）， can down-regulate multiple signaling pathways related with virus infection， immune response， and epithelial damage. RT-qPCR results indicated that compared with the model group， the QBZPY group down-regulated the mRNA expression of Il1b， tumor necrosis factor （Tnf）， Cxcl2， Cxcl10， Ccl2， Nos2 and Ptgs2 induced by LPS in RAW264.7 cells （P＜0.05 or P＜0.01）. ConclusionBased on targeted transcriptome analysis， expert experience in TCM and artificial intelligence， QBZPY has been developed for the treatment of nonsevere COVID-19. The ethanol extract of QBZPY has been found to inhibit mRNA expression of several pro-inflammatory genes in a cellular inflammation model.

Acute respiratory distress syndrome is one of the common complications of sepsis syndrome, belonging to the "Chuan syndrome", "Baochuan", and "Chuantuo" in the TCM field, and the disease is mainly located in the lung. The main etiology and pathogenesis of sepsis syndrome is deficient healthy qi and blood stasis with toxin blocking collaterals. Blood stasis and toxin invade the lung, causing heat and toxin to burn the body fluid in the blood. Blood viscosity and poor circulation lead to the accumulation of blood stasis and toxin in the lung. Acute deficiency syndrome, heat toxin damaging qi, heat toxin burning body fluid deficiency with little ability to dissipate qi, resulting in deficiency of healthy qi, inability to regulate breathing, inability to consolidate body fluid, inability to promote blood circulation, causing phlegm, dampness, and blood stasis blocking the lung. This disease is characterized by blood stasis with toxin blocking collaterals, deficient lung qi, and obstruction of lung qi caused by phlegm, water, dampness, and blood stasis. Therefore, blood stasis with toxin blocking collaterals, as well as deficient healthy qi are TCM pathogenesis of ARDS with sepsis syndrome.