The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

The classic formula Mulisan is the 45th of the 93 formulas in the Catalogue of Ancient Classic Formulas （second batch） of Han medicine published by the National Administration of Traditional Chinese Medicine. It consists of Ostreae Concha， Astragali Radix， Ephedrae Radix et Rhizoma， and wheat， with the effect of replenishing qi and stopping sweating. It is a common formula in the clinical treatment with traditional Chinese medicine. This study analyzes the historical evolution， composition， dosage， original plants and their processing methods， decocting method， efficacy， indications， and modern clinical application of Mulisan by tracing， comparative analysis， and bibliometric methods. The results showed that Mulisan firstly appeared in the Pulse Classic written by WANG Shuhe in the Western Jin Dynasty. The formulation idea can be traced back to the Important Prescriptions Worth a Thousand Gold for Emergency in the Tang Dynasty. The herb composition， dosage， efficacy， and indications of Mulisan were first recorded in the Treatise on Diseases， Patterns， and formulas Related to Unification of the Three Etiologies in the Southern Song dynasty. In terms of original plants and their processing methods， Ostreae Concha is the shell of Ostrea rivularis， which should be calcined before use. Astragali Radix and Ephedrae Radix et Rhizoma are the dried roots of Astragalus membranaceus var. mongholicus and Ephedra sinica， respectively， the raw material of which should be used. Wheat is the dried mature fruit of T. aestivum， which can be used without processing， while the stir-fried fruit， being thin and deflated， demonstrates better effect. The composition of Mulisan is Ostreae Concha 8.26 g， Astragali Radix 8.26 g， Ephedrae Radix et Rhizoma 8.26 g， and wheat 7.92 g. The medicinal materials should be ground into coarse powder and decocted with 450 mL water to reach a volume of 240 mL， and the decoction should be taken warm. In modern clinical practice， Mulisan has a wide range of indications， including spontaneous sweating and night sweating caused by Yang deficiency or Qi deficiency. The clinical disease spectrum treated by Mulisan involves endocrine system diseases， neurological diseases， respiratory system diseases， and cancer. This formula plays a significant role in the treatment of internal medicine diseases in traditional Chinese medicine. This study aims to provide a scientific basis for the subsequent research， development， and clinical application of Mulisan.

Given the limitations of traditional scientific research methods in revealing the complex and dynamic evolution of disease pathomechanisms， this paper analyzes the current state and challenges of the traditional Chinese medicine （TCM） pathomechanism syndrome differentiation system within the framework of systems thinking. The challenges include insufficient experimental models， low data standardization， complex nonlinear characteristics， and difficulties in integrating expert experience. By leveraging qualitative-quantitative comprehensive integration methods， this paper proposes specific research strategies， including constructing qualitative models of pathomechanism evolution， employing mathematical models for validation and quantitative analysis to reveal pathomechanism patterns， and incorporating a "human-centered" approach to achieve human-machine collaboration. These strategies aim to provide insights for the modernization and development of a new TCM pathomechanism syndrome differentiation system.

The modern Silk Road spirit advocating for win-win cooperative partnerships, aligns with the target of the “Belt and Road” Initiative, which provides new opportunities for collaboration on tropical disease control among countries along the “Belt and Road”. The modern Silk Road spirit may effectively facilitate tropical disease control programmes and improve disease control concepts and approaches through collaborative research, information sharing, infrastructure development, and joint efforts in pharmaceuticals and vaccine development; however, there are still multiple challenges that require to be overcome, including political and cultural differences, and data sharing. Therefore, countries participating in the “Belt and Road” Initiative need to work together with mutual respects, build effective collaborative mechanisms and improve communications to jointly facilitate the sustainable development of global tropical disease control programmes and cultural exchange, so as to contribute to global health and prosperities. This article discusses the contribution of the modern Silk Road spirit to facilitating global tropical disease control programmes in the context of the “Belt and Road” Initiative.

OBJECTIVE To assess the efficacy and safety of different treatment modalities for moderate to severe Henoch- Schönlein purpura nephritis （HSPN）. METHODS Literature searches were conducted in the CNKI， VIP， Wanfang Data， SinoMed， PubMed， OVID， Web of Science， Embase， and the Cochrane Library to collect randomized controlled trials （RCTs） and cohort studies on the treatment of moderate to severe HSPN with 12 intervention measures： monotherapy with glucocorticoid （GC）， as well as cyclophosphamide， mycophenolate mofetil （MMF）， Tripterygium wilfordii multiglucoside （TWM）， leflunomide， mizoribine， tacrolimus， cyclosporin A， hemoperfusion， tonsillectomy combined with GC， and double filtration plasmapheresis （DFPP） combined with GC and cyclophosphamide or mycophenolate mofetil. The search period was from the inception of the databases to March 2024. After literature screening， data extraction， and quality assessment， a network meta- analysis was performed using Stata 16.0 software. RESULTS A total of 28 articles were included， with 14 RCTs and 14 cohort studies， involving 1 746 patients. The network meta-analysis results showed the combination of tacrolimus and GC had the highest probability of being the best in overall remission rate， followed by the combination of TWM and GC， and DFPP combined with GC and MMF. The combination of leflunomide and GC had the highest probability of being the best in complete remission rate， followed by the combination of mizoribine and GC， and DFPP combined with GC and cyclophosphamide. The combination of mizoribine and GC had the highest probability of being the best in terms of reducing 24-hour urinary protein quantification， followed by DFPP combined with GC and MMF， and the combination of leflunomide and GC. Moreover， the combination of tacrolimus and GC had the highest probability of being the best in safety， followed by the combination of cyclosporin A and GC， and the combination of leflunomide and GC. CONCLUSIONS Compared to other treatment methods， the combination therapy of tacrolimus and GC shows better efficacy and safety in the treatment of moderate to severe HSPN.

Objective: To analyze the developmental trajectories of middle school students loneliness and social support, as well as to explore the interaction between loneliness and social support, so as to provide the evidence based support for the mental health development of adolescents. Methods: A total of 989 first year students from four public middle schools in Xiangxi Tujia and Miao Autonomous Prefecture, Hunan Province were selected for three follow up surveys by a cluster random sampling method (T1:March 2023, T2:June 2023, T3:December 2023). The UCLA Loneliness Scale-20 (ULS-20) and Social Support Scale for University Students (SSSUS) were employed for questionnaire data collection. The growth mixture modeling was utilized to test the developmental trajectories of loneliness and social support among middle school students, while the cross lagged analysis was performed to investigate their mutual influence. Results: The scores for loneliness and social support in T1, T2 and T3 were (43.1±5.8, 42.5± 6.8 , 42.0±6.9; 55.9±12.0, 60.7±15.7, 60.4±16.7), respectively. Correlational analysis revealed a significant negative correlation between loneliness levels (T1, T2, T3) and social support (T1, T2, T3) ( r =-0.47 to -0.36, P <0.01). Growth mixture modeling indicated a linear declining trend of middle school students loneliness, and the developmental trajectory of social support showed a linear increasing trend, with significant individual differences in initial levels and rates of change ( P <0.05). Cross lagged analyses revealed that loneliness levels at T1 negatively predicted social support scores at T2 ( β =-0.16), and loneliness levels at T2 negatively predicted social support scores at T3 ( β =-0.12) ( P <0.05). Additionally, prior loneliness positively predicted its subsequent levels, with path coefficients of 0.58 and 0.47, respectively ( P <0.05). Social support scores at T1 negatively predicted loneliness levels at T2 ( β =-0.10), while scores at T2 negatively predicted loneliness levels at T3 ( β =-0.15) ( P <0.05). Prior loneliness also positively predicted its subsequent levels, with path coefficients of 0.43 and 0.44, respectively ( P <0.05). Conclusion The developmental trajectory of middle school students loneliness demonstrates a decreasing trend, while that of social support exhibits a linear increasing trend, indicating a longitudinal causal relationship between loneliness and social support.

Coronary artery calcifications (CAC) is an independent risk factor for cardiovascular disease (CVD). It has been revealed that this condition can be automatically quantified through computerize tomographic (CT) scan contained in radiotherapy plan for patients with breast cancer, with which, physicians can identify the patients with increased risk of CVD after radiotherapy prematurely and take intervention measures in advance. In this article, the current literature and research progress on the correlation between CAC and cardiotoxicity in patients with breast cancer after radiotherapy were reviewed, expecting to provide a strategy to reduce the CVD risk in patients with breast cancer after radiotherapy.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.

Surgical treatment is one of the most important forms of treatment in patients with gallbladder cancer. With the development of minimally invasive technology, the feasibility, safety and efficacy of minimally invasive approaches such as laparoscopic or robotic-assisted radical cholecystectomy for gallbladder cancer have received continuous attention.For patients with an early T‐stage (Tis or T1a), laparoscopic simple cholecystectomy is safe and economical, with a good prognosis for postoperative patients, and it has been widely accepted and performed. Radical resection of advanced gallbladder cancer requires resection of the gallbladder, its liver bed, and other neighboring invaded organs, as well as clearance of regional lymph nodes, which requires experienced gallbladder cancer treatment teams to strictly grasp the indications, select appropriate patients, and formulate a good surgical strategy to ensure the therapeutic effect. Meanwhile, robot-assisted radical resection for gallbladder cancer has been performed in a few centers and shows good clinical potential, but more high-quality studies are needed to further evaluate its value in gallbladder cancer treatment.

Objective:To investigate the causal relationship between intestinal flora and benign biliary diseases by genome-wide Mendelian randomization.Methods:This is a retrospective observational study. The data from the genome-wide association study of the gut microbiota from 18 340 samples from the MiBioGen consortium were selected as the exposure group,and the data from the genome-wide association study of biliary tract diseases were obtained from the FinnGen consortium R8 as the outcome group. There were 1 491 cases of primary sclerosing cholangitis,32 894 cases of cholelithiasis,3 770 cases of acalculous cholecystitis,and 34 461 cases of cholecystitis. Single nucleotide polymorphisms were screened as instrumental variables,and the Mendelian randomization method was used to infer the causal relationship between exposures and outcomes. The inverse variance weighting method (IVW) was used as the main basis, supplemented by heterogeneity,pleiotropy and sensitivity tests.Results:Coprococcus 2 was associated with a reduced risk of cholelithiasis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.012) and cholecystitis (IVW OR=0.88,95% CI:0.80 to 0.97, P=0.011). Coprococcus 3 was associated with cholelithiasis (IVW OR=1.15,95% CI:1.02 to 1.30, P=0.019) and acalculous cholecystitis(IVW OR=1.48, 95% CI: 1.08 to 2.04, P=0.016) and cholecystitis (IVW OR=1.17, 95% CI: 1.02 to 1.33, P=0.020). Peptococcus was associated with an increased risk of cholelithiasis (IVW OR=1.08, 95% CI:1.02 to 1.13, P=0.005) and cholecystitis (IVW CI=1.07, 95% CI:1.02 to 1.13, P=0.010). Clostridiumsensustricto 1 was associated with an increased risk of cholelithiasis (IVW OR=1.16,95% CI:1.02 to 1.31, P=0.020) and cholecystitis (IVW OR=1.16, 95% CI:1.03 to 1.30, P=0.015). Eubacterium hallii was associated with an increased risk of primary sclerosing cholangitis (IVW OR=1.43, 95% CI: 1.03 to 1.99, P=0.033). Eubacterium ruminantium (IVW OR=0.87, 95% CI: 0.76 to 1.00, P=0.043) and Methanobrevibacter (IVW OR=0.81, 95% CI: 0.68 to 0.98, P=0.027) were associated with a reduced risk of acalculous cholecystitis. Conclusions:Eight intestinal bacterial genera maybe play pathogenic roles in benign biliary diseases. Eubacterium hallii can increase the risk of primary sclerosing cholangitis. Peptococcus and Clostridiumsensustricto 1 can increase the risk of cholelithiasis and generalized cholecystitis. Coprococcus 3 have multiple correlations with biliary stones and inflammation.