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.

Post-traumatic stress disorder (PTSD) is a relatively common but complex mental illness with a range of diverse risk factors. Typical symptoms include the re-experience or avoidance of traumatic events, cognitive impairment, and hypervigilance. While the exact pathogenesis of PTSD is unclear, many studies indicate that epigenetic regulation plays a key role in its development. Specifically, numerous studies have indicated that the levels of histone acetylation and methylation, DNA methylation, and noncoding RNA are altered in PTSD patients. Further to this, natural products have been found to achieve epigenetic regulation of PTSD by regulating the expression of epigenetic enzymes, long noncoding RNA (lncRNA), and miRNA, thereby playing a role in improving PTSD symptoms. To date, however, no epigenetic regulation related drugs have been used in the treatment of PTSD. Furthermore, while natural products that can epigenetically regulate PTSD have received increasing levels of attention, there have not yet been any systematic reports on the topic. Here, we summarized the roles and mechanisms of natural products in the epigenetic regulation of PTSD, providing a novel and unique perspective that will help to guide the development and application of new PTSD treatments.

Objective To analyze the characteristics of conventional ultrasound and contrast-enhanced ultrasound(CEUS)in hypovascular renal tumors,and to explore the application value of combining the 2 methods in diagnosing benign and malignant hypovascular renal tumors.Methods The conventional ultrasound and CEUS data of 104 hypovascular renal tumors(76 benign lesions[benign group]and 28 malignant lesions[malignant group])from 99 patients,who were confirmed by postoperative pathology,biopsy pathology or computed tomography(CT)/magnetic resonance imaging(MRI)enhancement combined with long-term follow-up in Ruijin Hospital,Shanghai Jiao Tong University School of Medicine and its Wuxi Branch from Oct.13,2009 to Oct.26,2022,were retrospectively analyzed.The location,size,internal echo,morphology,internal and peripheral blood supply of the lesions were observed by conventional ultrasound,and the perfusion mode,regression pattern,perfusion uniformity and ring enhancement signs were observed by CEUS.Taking the pathological results or confirmed results of CT/MRI enhancement combined with long-term follow-up as the gold standard,the value of conventional ultrasound combined with CEUS in the differential diagnosis of benign and malignant hypovascular renal tumors was analyzed.Results There were significant differences in gender,age of patients and internal echo,contrast agent regression and ring enhancement signs of lesions between the 2 groups(all P＜0.05).The malignant tumors were mostly found in males(78.6％,22/28)with an average age of(58.29±11.76)years old;the masses were mostly hypoechoic(64.3％,18/28),and rapid washout was predominant with CEUS(60.7％,17/28).In the benign group,most of the patients were female(55.3％,42/76),with an average age of(50.64±14.88)years old;the majority of the masses were hyperechoic(64.5％,49/76),and CEUS showed simultaneous washout as the main lesion(56.6％,43/76).Three patients(10.7％,3/28)with ring enhancement signs were all malignant.The diagnostic accuracy(82.7％)and specificity(88.2％)for benign and malignant hypovascular renal tumors were relatively high when combining the diagnostic indicators of ring enhancement signs and hypoechoic.The diagnostic sensitivity(85.7％)and negative predictive value(92.3％)were relatively high when combining the 3 diagnostic indicators of ring enhancement,hypoechoic,and rapid washout.Conclusion Conventional ultrasound combined with CEUS has significant clinical practical value in the differential diagnosis of benign and malignant hypovascular renal tumors.The ring enhancement sign is highly specific in the diagnosis of malignant hypovascular renal tumors.However,if this sign is not significant and conventional ultrasound shows hypoechoic or CEUS exhibits rapid washout,there is a strong suggestion that the mass may be a malignant lesion.

ObjectiveTo compare the differences in intestinal absorption of nanophase（NP） formed by single decoction and combined decoction of Ginseng Radix et Rhizoma（GRR） and Zingiberis Rhizoma Recens（ZRR） in rats， and to investigate the effects of new NP formed by the combined decoction on the absorption of main components in GRR and ZRR. MethodDifferential centrifugation and dialysis techniques were used to enrich NP in the single and combined decoctions of GRR and ZRR， respectively. The microstructure， particle size， Zeta potential and concentration of the NP were analyzed by transmission electron microscope， particle size analyzer and nanoparticle tracking analyzer. Based on everted gut sac model， the index components in the intestinal absorption solution of NP from the single and combined decoctions were analyzed by ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）. The per unit area actual value of cumulative intestinal absorption（Q_actual）， absorption rate constant（K_a） and apparent permeability coefficient（P_app） were used as the evaluating indexes to investigate the absorption characteristics of the aforementioned NP in the duodenum， jejunum， ileum and colon. ResultIrregularly spherical NP was present in the single and combined decoctions， and the contents of components in NP of the combined decoction were mostly lower than those in the single decoction. In these NP， ten components could be absorbed into the intestinal sac， with the main absorption site being the small intestine， and the P_app was greater than 1×10^-5 cm·min^-1. Compared with NP in the single decoction， the Q_actual and K_a of ginsenoside Rb₁， ginsenoside Rf， 4-gingerol and 6-shogaol were significantly increased in NP of the combined decoction， while ginsenoside Re and 6-gingerol were significantly decreased（P<0.01）. Except for ginsenoside Re and ginsenoside Rd， the P_app of the remaining constituents was significantly increased in NP of the combined decoction（P<0.01）. In addition， the maximum intestinal segment site of Q_actual was shifted forward for ginsenoside Rb₁， ginsenoside Rd and ginsenoside Ro， while shifted backward for ginsenoside Rg₁， ginsenoside Re and 8-gingerol. The maximal intestinal segment sites of K_a and P_app of ginsenoside Rb₁， ginsenoside Rg₁， ginsenoside Rd and ginsenoside Ro shifted forward， while ginsenoside Re and 4-gingerol were shifted backward. ConclusionThe combined decoction of GRR and ZRR is helpful to promote the absorption of the effective components of the two， and changes the absorption behavior of the effective components in some intestinal segments. This study provides a reference for the subsequent research on the compatibility mechanism of the two medicines.

Objective:To evaluate the prognosis of patients with primary thyroid malignant lymphoma (PTL) treated with total thyroidectomy alone or in combination with R-CHOP chemotherapy, and analyze the factors influencing their prognosis.Methods:A retrospective analysis was conducted on 62 patients with PTL admitted to the Hematology Department of Shanxi Provincial Cancer Hospital from Jan. 2009 to Jan. 2020. The patients were with an average age of (63.51±9.83) years, with 20 males and 42 females. According to Ann Arbor staging and patients' wishes, 10 cases received simple thyroidectomy, 47 cases received total thyroidectomy +R-CHOP, and 5 cases received total thyroidectomy +R-CHOP+ radiotherapy. After 3 months of treatment, the short-term curative effect was collected. According to the prognosis of patients after 24 months of follow-up, the dead cases were classified into bad group and the surviving cases into good group. Single factor and LASSO regression dimensionality reduction were used to screen the influencing factors, and Logistic regression analysis was used to analyze the influencing factors of PTL prognosis.Results:Among 62 patients with PTL, 21 (33.87%) had complete response (CR), 27 (43.55%) had partial response (PR), 9 (14.52%) had stable disease (SD), and 5 (8.06%) had progressive disease (PD). After a follow-up of 24 months, the mortality rate among 10 patients who underwent surgical treatment alone was 90% (9/10), the mortality rate among those who underwent surgical treatment combined with R-CHOP therapy was 19.15% (9/47) ,18 deaths were categorized as having a poor prognosis, while 44 survivors were classified as having a favorable prognosis.Univariate, LASSO regression screening, and Logistic regression analysis showed that Ann Arbor staging ( OR=5.105), pathological type ( OR=3.622), international prognostic index (IPI) score ( OR=2.709), treatment method ( OR=0.730), hemoglobin ( OR=0.392), and lactate dehydrogenase (LDH) ( OR=6.469) were factors affecting the prognosis of PTL (all P<0.05) . Conclusions:The combined use of total resection and R-CHOP treatment for patients has a superior prognosis compared to patients undergoing total resection alone. Furthermore, the prognosis of patients is also influenced by factors such as Ann Arbor staging and IPI scoring. Based on this, clinical care plans can be refined to improve the prognosis.

Objective:To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on the treatment of relapsed/refractory multiple myeloma (RRMM) with chimeric antigen receptor T cell (CAR-T) therapy.Methods:A retrospective cohort study. The clinical data of 168 patients with RRMM who underwent CAR-T therapy at the Department of Hematology, Xuzhou Medical University Hospital from 3 January 2020 to 13 September 2022 were analyzed. Patients were classified into a transplantation group (TG; n=47) and non-transplantation group (NTG; n=121) based on whether or not they had undergone ASCT previously. The objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and the levels of CD3, CD4, CD8, CD19, CD56 and natural killer (NK) cells before CAR-T infusion were analyzed by χ2 test, Kaplan-Meier method and independent sample t-test. Results:Among 168 patients with RRMM, 98 (58.3%) were male. The median age of onset was 57 (range 30-70) years. After CAR-T therapy, the ORR of patients was 89.3% (92/103) in the NTG and 72.9% (27/73) in the TG. The ORR of the NTG was better than that of the TG ( χ2=5.71, P=0.017). After 1 year of CAR-T therapy, the ORR of the NTG was 78.1% (75/96), and that of the TG was 59.4% (19/32). The ORR of the NTG was better than that of the TG ( χ2=4.32, P=0.038). The median OS and PFS in the NTG were significantly longer than those in the TG (OS, 30 vs. 20 months; PFS, 26 vs. 12 months; both P<0.05). The CD4 level before CAR-T infusion in the TG was significantly lower than that in the NTG (25.65±13.56 vs. 32.64±17.21; t=-2.15, P=0.034), and there were no significant differences in the counts of CD3, CD8, CD19, CD56, and NK cells between the TG and NTG (all P>0.05). Conclusion:Among patients suffering from RRMM who received CAR-T therapy, patients who did not receive ASCT had significantly better outcomes than those who had received ASCT previously, which may have been related to the CD4 level before receiving CAR-T therapy.

Objective To investigate the clinical value of contrast-enhanced ultrasound(CEUS)in differential diagnosis between benign and malignant gallbladder lesions which diameter more than 1 cm.Methods A retrospective analysis included CEUS data of 142 cases with gallbladder lesions diameter more than 1 cm.All lesions were confirmed by surgical pathology,enhanced CT/MRI or clinical diagnosis with following up more than 2 years.To summarize the CEUS characteristics of benign and malignant gallbladder lesions over 1 cm in diameter,the CEUS characteristics of benign and malignant gallbladder lesions diameter more than 1 cm were analyzed,referring to the gallbladder CEUS guidelines.The contrast medium washout before 35 s and 60 s were used as the combined diagnosis with CEUS standard to identify gallbladder cancer,and the diagnostic efficiency was calculated respectively.Results There were statistical differences between the malignant group and the benign group in terms of CEUS enhancement pattern,contrast arrival time,washout time,and gallbladder wall continuity,as well as enhancement levels(P<0.001).The sensitivity,specificity,accuracy in the diagnosis of gallbladder malignant lesions were 93.0%,83.8%,and 86.6%based on CEUS standard.The sensitivity,specificity and accuracy of diagnosis gallbladder malignant lesions were increased to 93.0%,92.9%and 93.0%when combined with washout before 35 s of contrast medium.Conclusions CEUS is highly valuable in differentiating benign and malignant gallbladder lesions diameter more than 1 cm.Combined with contrast medium washout before 35 s is helpful to improve the ability of differentiating benign and malignant gallbladder lesions.

Stimulus-responsive transdermal drug delivery systems can achieve specific drug release and improve drug utilization. According to the different stimulation modes， these preparations can be divided into endogenous stimulus-responsive， exogenous stimulus-responsive and combined stimulus-responsive transdermal drug delivery systems. The endogenous stimulation- responsive transdermal drug delivery system can respond specifically to changes in temperature and pH of the lesion site through carrier materials， so as to deliver drugs to the target site. Exogenous stimulus-responsive transdermal drug delivery system can use light， heat， magnetic， electric and other external stimulation to make the carrier material phase change， so as to achieve drug delivery. The combined stimulus-responsive transdermal drug delivery system is a combination of two or more stimulus-responsive percutaneous drug delivery systems， such as temperature-pH dual-responsive drug delivery system. At present， the relevant studies of stimulus-responsive transdermal drug delivery systems are mostly in the experimental stage， and further evaluation of stability， toxicity and skin irritation is needed in the future to lay a theoretical foundation for clinical application.

Objective:To explore the technical points and efficacy of gradual traction-unlocking closed reduction technique (GT-UCRT) for Tile C old pelvic fractures.Methods:From August 2012 to June 2021, 6 patients with Tile C old pelvic fracture were treated and followed up at Department of Orthopedics, The Fourth Medical Center, General Hospital of Chinese PLA. They were 4 males and 2 females with an age of (35.8±10.5) years. By Tile classification: 4 cases of type C1.2, 1 case of type C1.3, and 1 case of type C2; time from injury to surgery: 153.8 (64.3, 204.8) days. The 6 patients were treated with GT-UCRT. The time for gradual traction reduction, operation time, hospital stay, intraoperative blood loss and complications were recorded. The modified Matta score was used to evaluate the reduction quality of pelvic fractures, and the Majeed score was used to evaluate the pelvic function at the last follow-up.Results:The 6 patients were followed up for (40.3±22.9) months (from 12 to 72 months) after surgery. The time for gradual traction reduction was (26.7±4.6) days, operation time (119.2±4.6) minutes, hospital stay (11.5±2.9) days, and intraoperative blood loss (533.3±189.6) mL. By the modified Matta score, the pelvic reduction after surgery was rated as satisfactory in 5 cases and as unsatisfactory in 1 case. The length disparity between both lower limbs in the 6 patients was (6.9±1.6) cm before surgery and (1.0±0.4) cm immediately after surgery, showing a statistically significant difference ( t=11.135, P<0.001). One fracture healed 3 months after surgery and 5 fractures 6 months after surgery. The Majeed pelvic score at the last follow-up was (80.8±9.0) points for the 6 patients, yielding 2 excellent cases, 3 good cases and 1 fair case. Delayed wound healing was reported in 1 patient, calf intermuscular venous thrombosis in 2 cases, and emotional anxiety and sleep disorder in 1 patient. No new lumbosacral plexus injury was found in any patient. Conclusions:In the treatment of Tile C old pelvic fractures, since our self-designed GT-UCRT combines the advantages of Ilizarov technique and unlocking closed reduction technique, it can not only protect the lumbosacral plexus but also obtain satisfactory reduction of the fracture.

S-adenosyl-l-methionine (SAM) is ubiquitous in living organisms and plays important roles in transmethylation, transsulfuration and transamination in organisms. Due to its important physiological functions, production of SAM has attracted increasing attentions. Currently, researches on SAM production mainly focus on microbial fermentation, which is more cost-effective than that of the chemical synthesis and the enzyme catalysis, thus easier to achieve commercial production. With the rapid growth in SAM demand, interests in improving SAM production by developing SAM hyper-producing microorganisms aroused. The main strategies for improving SAM productivity of microorganisms include conventional breeding and metabolic engineering. This review summarizes the recent research progress in improving microbial SAM productivity to facilitate further improving SAM productivity. The bottlenecks in SAM biosynthesis and the solutions were also addressed.
S-Adenosylmethionine/metabolism* ; Plant Breeding ; Fermentation ; Metabolic Engineering