OBJECTIVE To explore the changes and correlations of color， components and anti-tumor activity of Gelsemium elegans during sand-frying processing， so as to provide a reference for the toxicity-attenuating and efficacy-preserving processing as well as quality control of sand-fried G. elegans decoction pieces.METHODS Raw G.elegans and its processed products prepared by sand-frying for 15， 30， 75， 105 and 120 s were taken as test samples. The chromatic values， contents of total alkaloids and seven main active components （gelsemine， humantenine， koumine， gelsenicine， etc.） were determined. Their in vitro anti-tumor activity was investigated. The correlations between color and component contents， as well as between total alkaloid content and anti-tumor activity were analyzed.RESULTS The color of G.elegans samples generally darkened after sand-frying， and the total color difference （Δ E * ） of samples sand-fried for 75 s was greater than 20. At the initial stage of sand-frying （15-30 s）， the total alkaloid content in processed products decreased sharply compared with the raw material； at the later-stage of sand-frying （75-105 s）， the declining rate of total alkaloid content slowed down and tended to be stable. The contents of gelsenicine and humantenidine in processed products dropped drastically at 30 s of sand-frying， while the contents of koumine and sempervirine decreased substantially （by about 80%） after 75 s of sand-frying and then gradually tended to be stable. The anti-HepG2 cell proliferation activity of each processed product decreased with the extension of frying time. Correlation analysis demonstrated that color brightness and yellow-blue chromaticity were significantly positively correlated with the contents of total alkaloids and all determined active components except gelsemine （ P ＜0.05 or P ＜0.01）； red-green chromaticity was significantly positively correlated with the contents of koumine， sempervirine， gelsemivirine and humantenidine （ P ＜0.05 or P ＜0.01）； Δ E * was significantly negatively correlated with the contents of total alkaloids and all determined active components except gelsemine. Besides， total alkaloid content was significantly negatively correlated with the half maximal inhibitory concentration of the samples on HepG2 cells （ P ＜0.05 or P ＜0.01）.CONCLUSIONS With the prolongation of sand-frying time， the color of sand-fried G.elegans decoction pieces gradually turned brownish-brown， the contents of seven active components and total alkaloids decreased progressively， and its anti-HepG2 cell activity showed an overall downward trend. Sand-frying for 75 s serves as a critical turning-point for the above-mentioned changes.

ObjectiveTo analyze the adverse reactions associated with the clinical use of Banxia （Rhizoma Pinelliae）- Wutou （Aconitum） in the same formula， with the aim of providing a reference for the safety of their clinical application. MethodsLiterature on the clinical application of antagonistic herbs "Banxia-Wutou" used in the same formula， published from January 1st， 2014， to June 30th， 2023， was retrieved from databases including CNKI， VIP， Wanfang， SinoMed， PubMed， Cochrane Library， and Embase. A database was established， and information related to adverse reactions was extracted， including descriptions， classifications， specific manifestations， management and outcomes， patients' primary diseases （western medicine diseases and traditional Chinese medicine diagnoses and syndromes）， and medication information （dosage， ratio， administration routes， and dosage forms）. ResultsA total of 79 researches simultaneously used antagonistic herbs Banxia-Wutou in the same formula and reported associated advers reactions. Gastrointestinal adverse reactions were the most common， with 8 studies reporting management of adverse reactions and 3 studies reporting improvement with no intervention. Among the 11 researches， the adverse reaction relieved to extant， while other 69 researches didn't report the managment of adverse reaction and its prognosis. For the primary disease in western medicine system， chronic bronchitis and chronic obstructive pulmonary disease （COPD） were most common， while gastric pain was the most common symptom in traditional Chinese medicine with spleen and kidney deficiency and spleen stomach cold deficiency being the most frequent syndromes. The most common Banxia dosage was 10 g， while for the Wutou， Fuzi （Radix Aconiti Lateralis Praeparata） was predominant with the highest dose at 15 g. The most frequent herbal combination was Banxia-fuzi， with a 1∶1 ratio. The main administration route was oral， and the primary dosage form was decoction. ConclusionGastrointestinal adverse reactions are the most common in the clinical use of Banxia-Wutou antagonistic herb combinations. Research on the safety of "Banxia-Wutou" combinations should focus on respiratory system diseases and spleen-stomach related conditions.

Objective:To analyze clinical characteristics of primary pancreatic lymphoma (PPL) patients.Methods:Clinical features of 22 patients diagnosed as PPL admitted to Peking Union Medical College Hospital from January 2002 to May 2023 were analyzed retrospectively.Results:The median age was 56.4±13.3 years. The median time from onset to diagnosis was 1.0 (1.0, 3.0) months. The main clinical manifestations were abdominal pain (15/22), weight loss (14/22) and jaundice (10/22). Elevated lactate dehydrogenase (LDH) was observed in 15/20 (75%) patients. Only 2 (2/9, 22.2%) patients had increased CA199 levels and 2 (2/9, 22.2%) patients had increased CEA levels. The maximum tumor diameter was 5.0 (3.8, 6.9) cm. Contrast-enhanced CT mostly showed low enhancement lesions. Major pancreatic duct dilatation were rare on CT scan (4/20). Fifteen patients were confirmed by pancreatic pathology, of which 8 were obtained by surgery, 4 were obtained by CT or ultrasound-guided percutaneous biopsy, and 3 were obtained by EUS-FNA. The main pathological type was diffuse large B-cell lymphoma (14/22). 19 patients received chemotherapy, and 6 patients died with a median follow-up of 5.0 (1.5, 35.5) months.Conclusions:PPL is rare and easy to be misdiagnosed. Elevated LDH levels, normal tumor markers, and non-dilatation of main pancreatic duct are important diagnostic clues. It is important to obtain pathology by EUS-FNA and other methods for definite diagnosis.

Objective:Acute kidney injury (AKI) is one of the common complications in critically ill septic patients, which is associated with increased risks of death, cardiovascular events, and chronic renal dysfunction. The duration of AKI and the renal function recovery status after AKI onset can affect the patient prognosis. Nevertheless, it remains controversial whether early recovery status after AKI is closely related to the prognosis in patients with sepsis-associated AKI (SA-AKI). In addition, early prediction of renal function recovery after AKI is beneficial to individualized treatment decision-making and prevention of severe complications, thus improving the prognosis. At present, there is limited clinical information on how to identify SA-AKI patients at high risk of unrecovered renal function at an early stage. The study aims to investigate the association between early recovery status after SA-AKI, identify risk factors for unrecovered renal function, and to improve patients ' quality of life.Methods:We retrospectively analyzed clinical data of septic patients who were admitted to the intensive care unit (ICU) and developed AKI within the first 48 hours after ICU admission in the Second Xiangya Hospital and the Third Xiangya Hospital of Central South University from January 2015 to March 2017. Sepsis was defined based on the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). AKI was diagnosed and staged according to the 2012 Kidney Disease:Improving Global Outcomes (KDIGO) guideline. SA-AKI patients were assigned into 3 groups including a complete recovery group, a partial recovery group, and an unrecovered group based on recovery status at Day 7 after the diagnosis of AKI. Patients ' baseline characteristics were collected, including demographics, comorbidities, clinical and laboratory examination information at ICU admission, and treatment within the first 24 hours. The primary outcome of the study was the composite of death and chronic dialysis at 90 days, and secondary outcomes included length of stay in the ICU, length of stay in the hospital, and persistent renal dysfunction. Multivariate regression analysis was performed to evaluate the prognostic value of early recovery status after AKI and to determine the risk factors for unrecovered renal function after AKI. Sensitivity analysis was conducted in patients who still stayed in hospital on Day 7 after AKI diagnosis, patients without premorbid chronic kidney disease, and patients with AKI Stage 2 to 3.Results:A total of 553 SA-AKI patients were enrolled, of whom 251 (45.4％), 73 (13.2％), and 229 (41.4％) were categorized as the complete recovery group, the partial recovery group, and the unrecovered group, respectively. Compared with the complete or partial recovery group, the unrecovered group had a higher incidence of 90-day mortality (unrecovered vs partial recovery or complete recovery: 64.2％ vs 26.0％ or 22.7％; P<0.001) and 90-day composite outcome (unrecovered vs partial recovery or complete recovery:65.1％vs 27.4％or 22.7％;P<0.001). The unrecovered group also had a shorter length of stay in the hospital and a larger proportion of progression into persistent renal dysfunction than the other 2 groups. After adjustment for potential confounders, patients in the unrecovered group were at an increased risk of 90-day mortality (HR=3.50, 95％ CI 2.47 to 4.96, P<0.001) and 90-day composite outcome (OR=5.55, 95％CI 3.43 to 8.98, P<0.001) when compared with patients in the complete recovery group, but patients in the partial recovery group had no significant difference (P>0.05). Male sex, congestive heart failure, pneumonia, respiratory rate>20 beats per minute, anemia, hyperbilirubinemia, need for mechanical ventilation, and AKI Stage 3 were identified as independent risk factors for unrecovered renal function after AKI. The sensitivity analysis further supported that unrecovered renal function after AKI remained an independent predictor for 90-day mortality and composite outcome in the subgroups. Conclusion:The early recovery status after AKI is closely associated with poor prognosis in critically ill patients with SA-AKI. Unrecovered renal function within the first 7 days after AKI diagnosis is an independent predictor for 90-day mortality and composite outcome. Male sex, congestive heart failure, pneumonia, tachypnea, anemia, hyperbilirubinemia, respiratory failure, and severe AKI are risk factors for unrecovered renal function after AKI. Therefore, timely assessment for the renal function in the early phase after AKI diagnosis is essential for SA-AKI patients. Furthermore, patients with unrecovered renal function after AKI need additional management in the hospital, including rigorous monitoring, avoidance of nephrotoxin, and continuous assessment for the renal function, and after discharge, including more frequent follow-up, regular outpatient consultation, and prevention of long-term adverse events.

Background: Percutaneous transforaminal endoscopic discectomy (PTED) has been widely used in the treatment of lumbar degenerative diseases. Epidural injection of steroids can reduce the incidence and duration of postoperative pain in a short period of time. Although steroids are widely believed to reduce the effect of surgical trauma, the observation indicators are not uniform, especially the long-term effects, so the problem remains controversial. Therefore, the purpose of this paper was to evaluate the efficacy of epidural steroids following PTED. Methods: We searched PubMed, Embase, and the Cochrane Database from 1980 to June 2021 to identify randomized and non-randomized controlled trials comparing epidural steroids and saline alone following PTED. The primary outcomes included postoperative pain at least 6 months as assessed using a visual analogue scale (VAS) and the Oswestry Disability Index (ODI). The secondary outcomes included length of hospital stay and the time of return to work. Results: A total of 451 patients were included in three randomized and two nonrandomized controlled trials. The primary outcomes, including VAS and ODI scores, did not differ significantly between epidural steroids following PTED and saline alone. There were no significant intergroup differences in length of hospital stay. Epidural steroids were shown to be superior in terms of the time to return to work (P < 0.001). Conclusions Intraoperative epidural steroids did not provide significant benefits, leg pain control, improvement in ODI scores, and length of stay in the hospital, but it can enable the patient to return to work faster.

Objective:To explore the relationship between high performance liquid chromatography (HPLC) fingerprint and toxicity of Gelsemium elegans fermented by Ganoderma lucidum ( Ganoderma lucidum- Gelsemium elegans) for different time. Methods:Gelsemium elegans was processed by biphasic solid-state fermentation with Ganoderma lucidum. A total of 10 samples of Ganoderma lucidum- Gelsemium elegans were collected after fermentation for 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 days (sampling twice on day 27, number: S1-S10) and the fingerprints were determined by self-established HPLC. One hundred specific pathogen-free ICR mice were randomly divided into 10 groups (each group comprised 10 mice, half were male and half were female). The median lethal dose of Ganoderma lucidum- Gelsemium elegans collected after fermentation for 11 days in mice was used as the final concentration in toxicity test. S1-S10 Ganoderma lucidum- Gelsemium elegans solutions were prepared and given to 10 groups of mice respectively by gavage administration and the death of mice was observed. According to the calculation formula of grey correlation analysis, the correlation coefficients between the common peaks of S1-S10 Ganoderma lucidum- Gelsemium elegans in chromatographic fingerprint and their toxicity test results (death rate in mice) was calculated and the main components contributing to the toxicity of Ganoderma lucidum- Gelsemium elegans were analyzed. Results:A total of 17 common peaks were identified in the chromatographic fingerprint spectrum of S1-S10 Ganoderma lucidum- Gelsemium elegans. The mortalities in mice caused by S1-S10 of Ganoderma lucidum- Gelsemium elegans were 1.00, 1.00, 0.80, 0.70, 0.60, 0.60, 0.50, 0.40, 0, and 0, respectively. The grey correlation analysis showed that the correlation coefficients of common peak 7, 3, 6, 9, 1, 8, 17, and 12 to toxicity were 0.868, 0.838, 0.830, 0.828, 0.824, 0.820, 0.818, and 0.802, respectively. The chemical components represented by these 8 chromatographic peaks had more contribution to the toxicity of Ganoderma lucidum- Gelsemium elegans. Conclusions:With the extension of fermentation time, the toxicity of Ganoderma lucidum- Gelsemium elegans decreased gradually, and toxicity was the lowest at 27 days of fermentation. The toxicity of Gelsemium elegans after fermentation was the result of a join action from multiple components. The identification of the main toxicity components can provide a reference for the quality control of Ganoderma lucidum- Gelsemium elegans and the fermentation process optimization.

Objective:To explore the relationship between high performance liquid chromatography (HPLC) fingerprint and toxicity of Gelsemium elegans fermented by Ganoderma lucidum ( Ganoderma lucidum- Gelsemium elegans) for different time. Methods:Gelsemium elegans was processed by biphasic solid-state fermentation with Ganoderma lucidum. A total of 10 samples of Ganoderma lucidum- Gelsemium elegans were collected after fermentation for 9, 11, 13, 15, 17, 19, 21, 23, 25, 27 days (sampling twice on day 27, number: S1-S10) and the fingerprints were determined by self-established HPLC. One hundred specific pathogen-free ICR mice were randomly divided into 10 groups (each group comprised 10 mice, half were male and half were female). The median lethal dose of Ganoderma lucidum- Gelsemium elegans collected after fermentation for 11 days in mice was used as the final concentration in toxicity test. S1-S10 Ganoderma lucidum- Gelsemium elegans solutions were prepared and given to 10 groups of mice respectively by gavage administration and the death of mice was observed. According to the calculation formula of grey correlation analysis, the correlation coefficients between the common peaks of S1-S10 Ganoderma lucidum- Gelsemium elegans in chromatographic fingerprint and their toxicity test results (death rate in mice) was calculated and the main components contributing to the toxicity of Ganoderma lucidum- Gelsemium elegans were analyzed. Results:A total of 17 common peaks were identified in the chromatographic fingerprint spectrum of S1-S10 Ganoderma lucidum- Gelsemium elegans. The mortalities in mice caused by S1-S10 of Ganoderma lucidum- Gelsemium elegans were 1.00, 1.00, 0.80, 0.70, 0.60, 0.60, 0.50, 0.40, 0, and 0, respectively. The grey correlation analysis showed that the correlation coefficients of common peak 7, 3, 6, 9, 1, 8, 17, and 12 to toxicity were 0.868, 0.838, 0.830, 0.828, 0.824, 0.820, 0.818, and 0.802, respectively. The chemical components represented by these 8 chromatographic peaks had more contribution to the toxicity of Ganoderma lucidum- Gelsemium elegans. Conclusions:With the extension of fermentation time, the toxicity of Ganoderma lucidum- Gelsemium elegans decreased gradually, and toxicity was the lowest at 27 days of fermentation. The toxicity of Gelsemium elegans after fermentation was the result of a join action from multiple components. The identification of the main toxicity components can provide a reference for the quality control of Ganoderma lucidum- Gelsemium elegans and the fermentation process optimization.

Objective: Systematic evaluation of the correlation of HLA-DQB1 and HLA-DRB1 allele polymorphisms with caries, to provide reference for caries prevention and treatment. Methods: Relevant literature published before December 2020 was searched in the Cochrane Library, PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang, VIP, and CBM databases. Meta-analysis was performed using the R4.0.2 software to test for heterogeneity and evaluate the publication bias. Results : In total,10 case-control studies were included with 564 people in the case group and 676 people in the control group. The results of the Meta-analysis show that: ① HLA-DQB1*02 (OR=0.52, 95%CI=0.29-0.93, P < 0.05) and HLA-DRB1*09 (OR=0.34, 95%CI=0.21-0.58, P < 0.05) are protective factors of dental caries; ② HLA-DRB1*13 (OR=2.96, 95%CI=2.03-4.33, P < 0.05) and HLA-DRB1*14 (OR=1.95, 95%CI=1.26-3.02, P < 0.05) alleles are risk factors for the development of dental caries. The results of the subgroup analysis are: HLA-DRB1*07 is a caries susceptibility factor in the Chinese population (OR=0.48, 95% CI=0.24-0.97, P < 0.05), while it is not statistically significant in the Brazilian and Turkish populations; HLA-DRB1*11 is a caries protective factor in the saliva group (OR=2.26, 95% CI=1.46-3.52, P < 0.05). 3.52, P < 0.001), while it is a caries susceptibility factor in the blood group (OR=0.09, 95% CI=0.12-0.34, P < 0.001). Conclusion HLA-DRB1*13 and HLA-DRB1*14 alleles are caries susceptibility genes, and HLA-DQB1*02 and HLA-DRB1*09 have protective effects on the caries development. HLA-DRB1*07 is a caries susceptibility gene in the Chinese population; HLA-DRB1*11 is a caries protective gene in the saliva group. Due to the limited sample size and quality of the included studies, more high-quality studies will be included later for verification.

The cellular functions of proteins are maintained by forming diverse complexes. The stability of these com-plexes is quantified by the measurement of binding affinity, and mutations that alter the binding affinity can cause various diseases such as cancer and diabetes. As a result, accurate estimation of the binding stability and the effects of mutations on changes of binding affinity is a crucial step to understanding the biological functions of proteins and their dysfunctional consequences. It has been hypothesized that the stability of a protein complex is dependent not only on the residues at its binding interface by pairwise interactions but also on all other remaining residues that do not appear at the binding interface. Here, we computationally reconstruct the binding affinity by decomposing it into the contributions of interfacial residues and other non-interfacial residues in a protein complex. We further assume that the contributions of both interfacial and non-interfacial residues to the binding affinity depend on their local structural environments such as solvent-accessible surfaces and secondary structural types. The weights of all corresponding parameters are optimized by Monte-Carlo simulations. After cross-validation against a large-scale dataset, we show that the model not only shows a strong correlation between the absolute values of the experimental and calculated binding affinities, but can also be an effective approach to predict the relative changes of binding affinity from mutations. Moreover, we have found that the optimized weights of many parameters can capture the first-principle chemical and physical features of molecular recognition, therefore re-versely engineering the energetics of protein complexes. These results suggest that our method can serve as a useful addition to current computational approaches for predicting binding affinity and understanding the molecular mechanism of protein–protein interactions.

Objective To investigate the clinical applications of goal-directed fluid therapy for pancreatoduodenectomy. Methods A total of 40 patients undergoing pancreatoduodenectomy under general anesthesia were randomly divided into two groups, G and C, with 20 cases in each group. Goal-directed fluid therapy was used in Group G, whereas conventional fluid therapy was used in group C. The intraoperative hemodynamics, liquid management, duration of the first postoperative gastrointestinal ventilation, postoperative renal function, serum lactate, and the incidence of postoperative complications were recorded. Results Compared with group C, the CI increased and SVV decreased (P ＜ 0.05) at T3 to T5, and MAP increased at T4 to T5 (P ＜ 0.05). The amount of fluid infusion and total infusion in group G were less than that of group C (P ＜ 0.05), and the number of vasoactive drugs was greater than that of group C (P ＜ 0.05). The duration of the first postoperative gastrointestinal ventilation in group G was shorter than that of group C (P ＜ 0.05). There were no significant differences between the 2 groups for the incidence of serum lactate, BUN, Cr, and the incidence of postoperative complications (P＞ 0.05).Conclusion For major complex operations, such as pancreaticoduodenectomy, goal-directed fluid therapy can guide intraoperative fluid therapy more accurately with individual optimizations, and has more advantages in maintaining intraoperative hemodynamics stability and improving postoperative outcome.