Characterization of a novel anti-PVRIG antibody with Fc-competent function that exerts strong antitumor effects via NK activation in preclinical models.

Poliovirus receptor-related immunoglobulin domain-containing protein, or PVRIG, is a newly discovered immune checkpoint that has emerged as a promising target for cancer immunotherapy. It is primarily expressed on activated T and natural killer (NK) cells, and once engaged with its ligand, PVRL2, it induces inhibitory signaling in T cells, thereby promoting the functional exhaustion of tumor-infiltrating lymphocytes (TILs). Here, we characterized IBI352g4a, a novel humanized anti-PVRIG antibody with Fc-competent function, explored the mechanism of its antitumor activity in preclinical models, and systemically evaluated the contribution of FcrR engagement to PVRIG blockade-induced antitumor activity. IBI352g4a binds to the extracellular domain of human PVRIG with high affinity (Kd = 0.53 nM) and specificity, and fully blocks the interaction between PVRIG and its ligand PVRL2. Unlike other immune checkpoints, IBI352g4a significantly induced NK cell activation and degranulation, but had a minimal effect on T-cell activation in in vitro functional assays. IBI352g4a induced strong antitumor effect in several preclinic models, through in vivo mechanism analysis we found that both NK and T cells contribute to the antitumor effect, but NK cells play predominant roles. Specifically, a single dose of IBI352g4a induced significant NK cell activation in TILs, but T-cell activation was observed only after the second dose. Moreover, the Fc effector function is critical for both NK cell activation and treatment efficacy in vitro and in vivo. Our study, for the first time, demonstrates that both NK activation and FcrR engagement are required for antitumor efficacy induced by PVRIG blockade.

Determination of acetochlor by UPLC-MS3 in cells and its application to a cellular pharmacokinetic study.

The aim of this work was to develop a fast, simple, and reliable UPLC-MS3 method for the sensitive detection of acetochlor in biological samples. In MS3 mode, the ion transition m/z 270.1 â†’ 224.1→148.1 was chosen for quantification with butachlor as the internal standard. In the UPLC system, separation was performed on a UPLC column (2.1 × 50 mm ID, 1.7 µm) with 0.1 % FA in water and acetonitrile as mobile phases. After simple protein precipitation via acetonitrile, the method was well validated with good linearity (0.5-20 ng/mL, r > 0.995), accuracy (-3.70 %-2.98 %), and precision (<15 %). The selectivity and sensitivity were improved obviously in MS3 mode than that in MRM mode. The developed UPLC-MS3 method was successfully applied to the cellular pharmacokinetics study of acetochlor in MCF-7 cells.

Ultra-high-performance liquid chromatography with tandem mass spectrometry method for cellular toxicity and pharmacokinetic study of PEG1K polymers.

Polyethylene glycol (PEG) is one of the most commonly used polymers in drug delivery systems. The investigation of the pharmacokinetic behavior of PEG is important for revealing the toxicity and efficiency of PEG-related Nano-drug delivery systems. A high through-put and selective ultra-high-performance liquid chromatography with tandem mass spectrometry (UHPLC-MS/MS) method coupled with collision-induced dissociation (CID) in source technique was developed and validated to determine PEG1K polymers in cellular samples in this study. The countless precursor ions of PEG1K are dissociated in the source to generate numerous product ions which have different numbers of subunits. The transition of [M+H]+ precursor ions → product ions at m/z 177.1 (four subunits)→89.1 (two subunits) was selected to determine PEG1K due to its high sensitivity. The UHPLC-MS/MS method coupled with CID in the source showed good linearity over the range of 0.1-10 µg/mL. Intra-day and inter-day accuracies and precisions of the assay were all within ± 12.39%. The assay was successfully applied to a cellular pharmacokinetic study of PEG1K in human breast cancer cells. The cytotoxicity of PEG1K polymers was also studied and the results indicated that the cytotoxicity of PEG1K was not significant in the range of 5-1200 µg/mL.

Quantification of human serum albumin by combining chymotrypsin/trypsin digestion coupled with LC-MS/MS technique.

The quantification of albumin is important in clinical medicine because the concentration of albumin in biological fluids is closely related to human health. In this study, we developed a highly selective and robust assay to determine human serum albumin (HSA) in human plasma by combining chymotrypsin/trypsin digestion coupled with targeted LC-MS/MS technique. Human plasma samples were denatured, reduced, alkylated, and digested with both chymotrypsin and trypsin to generate surrogate peptides. A unique chymotryptic peptide (NAETF) arising from human serum albumin was finally selected for targeted LC-MS/MS detection and quantification. Numerous parameters related to the targeted LC-MS/MS assay were evaluated, including lower limit of quantitation (LLOQ), linearity range, enzyme digestion efficiency, accuracy and precision. The LC-MS/MS assay was linear in the concentration range 0.05-1 mg/mL with intra-day and inter-day precision <10.2% and accuracy ranging from -3.94% to 4.89%. The assay was successfully applied to determine HSA in 148 human plasma samples.

PI3K/AKT pathway promotes keloid fibroblasts proliferation by enhancing glycolysis under hypoxia.

Our previous study demonstrated altered glucose metabolism and enhanced phosphorylation of the PI3K/AKT pathway in keloid fibroblasts (KFb) under hypoxic conditions. However, whether the PI3K/AKT pathway influences KFb cell function by regulating glucose metabolism under hypoxic conditions remains unclear. Here, we show that when PI3K/AKT pathway was inactivated with LY294002, the protein expression of glycolytic enzymes decreased, while the amount of mitochondria and mitochondrial membrane potential increased. The key parameters of extracellular acidification rate markedly diminished, and those of oxygen consumption rate significantly increased after inhibition of the PI3K/AKT pathway. When the PI3K/AKT pathway was suppressed, the levels of reactive oxygen species (ROS) and mitochondrial ROS (mitoROS) were significantly increased. Meanwhile, cell proliferation, migration and invasion were inhibited, and apoptosis was increased when the PI3K/AKT pathway was blocked. Additionally, cell proliferation was compromised when KFb were treated with both SC79 (an activator of the PI3K/AKT pathway) and 2-deoxy-d-glucose (an inhibitor of glycolysis), compared with the SC79 group. Moreover, a positive feedback mechanism was demonstrated between the PI3K/AKT pathway and hypoxia-inducible factor-1α (HIF-1α). Our data collectively demonstrated that the PI3K/AKT pathway promotes proliferation and inhibits apoptosis in KFb under hypoxia by regulating glycolysis, indicating that the PI3K/AKT signalling pathway could be a therapeutic target for keloids.

Ultrafast and ultrastable FeSe2embedded in nitrogen-doped carbon nanofibers anode for sodium-ion half/full batteries.

Transition metal selenides are considered as promising anode materials for fast-charging sodium-ion batteries due to their high theoretical specific capacity. However, the low intrinsic conductivity, particle aggregation, and large volume expansion problems can severely inhibit the high-rate and long-cycle performance of the electrode. Herein, FeSe2nanoparticles embedded in nitrogen-doped carbon nanofibers (FeSe2@NCF) have been synthesized using the electrospinning and selenization process, which can alleviate the volume expansion and particle aggregation during the sodiation/desodiation and improve the electrical conductivity of the electrode. The FeSe2@NCF electrode delivers the outstanding specific capacity of 222.3 mAh g-1at a fast current density of 50 A g-1and 262.1 mAh g-1at 10 A g-1with the 87.8% capacity retention after 5000 cycles. Furthermore, the Na-ion full cells assembled with pre-sodiated FeSe2@NCF as anode and Na3V2(PO4)3/C as cathode exhibit the reversible specific capacity of 117.6 mAh g-1at 5 A g-1with the 84.3% capacity retention after 1000 cycles. This work provides a promising way for the conversion-based metal selenides for the applications as fast-charging sodium-ion battery anode.

Cellular toxicity and pharmacokinetic study of butachlor by ultra-performance liquid chromatography-tandem mass spectrometry based on tandem mass spectrometry cubed technique.

Butachlor is an aromatic amide compound that plays a role as a herbicide, a xenobiotic, and an environmental contaminant. The aim of this work was to develop a highly selective and sensitive ultra-performance liquid chromatography-tandem mass spectrometry method based on the tandem mass spectrometry cubed technique to determine butachlor in a biological matrix. Butachlor and internal standard acetochlor were separated on a Waters Acquity ultra-performance liquid chromatography BEH C18 column (2.1 × 50 mm, 1.7 µm) with gradient elution using 0.1% formic acid aqueous solution (A) and acetonitrile (B) as mobile phases. The transitions selected for tandem mass spectrometry cubed quantitative analysis in positive ion mode were: for butachlor, mass-to-charge ratio 312.2→238.1→162.1; for acetochlor, mass-to-charge ratio 270.1→224.0→148.1. The total running time for each sample was 5.5 min. The ultra-performance liquid chromatography-tandem mass spectrometry cubed method showed a linear relationship (R2 ≥ 0.995) in the concentration range of 0.5-100 ng/ml. The intra and interday accuracies are within the range of -10.6%-4.3% and precisions are between 4.48% and 13.14%. The novelty of the method is the use of tandem mass spectrometry cubed scanning mode, which improves selectivity and sensitivity. The results indicated that butachlor was cellular toxic. The safety of butachlor should be considered when it is used as a herbicide.

The Effect of Trans-Sutural Distraction Osteogenesis on Nasal Bone, Nasal Septum, and Nasal Airway in the Treatment for Midfacial Hypoplasia in Growing Patients.

The purposes of this study were to analyze the effect of trans-sutural distraction osteogenesis (TSDO) on nasal bone, nasal septum, and nasal airway in the treatment of midfacial hypoplasia. A total of 29 growing patients with midfacial hypoplasia who underwent TSDO by a single surgeon were enrolled. The 3-dimensional measurement of nasal bone and nasal septum changes was performed using computed tomography (CT) images obtained preoperatively (T0) and postoperatively (T1). One patient was selected to establish 3-dimensional finite element models to simulate the characteristics of nasal airflow field before and after traction. After traction, the nasal bone moved forward significantly ( P <0.01). The septal deviation angle was lower than that before traction (14.43±4.70 versus 16.86 ±4.59 degrees) ( P <0.01). The length of the anterior and posterior margin of the vomer increased by 21.4% ( P <0.01) and 27.6% ( P <0.01), respectively, after TSDO. The length of the posterior margin of the perpendicular plate of ethmoid increased ( P <0.05). The length of the posterior inferior and the posterior superior margin of the nasal septum cartilage increased ( P <0.01) after traction. The cross-sectional area of nasal airway on the deviated side of nasal septum increased by 23.0% after traction ( P <0.05). The analysis of nasal airflow field showed that the pressure and velocity of nasal airflow and the nasal resistance decreased. In conclusion, TSDO can promote the growth of the midface, especially nasal septum, and increase the nasal space. Furthermore, TSDO is conductive to improve nasal septum deviation and decrease nasal airway resistance.

Design, synthesis, biological evaluation and molecular docking study of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as novel HSP90 N-terminal inhibitors.

The molecular chaperone HSP90 plays an essential role in cancer occurrence and development. Therefore, it is an important target for the development of anticancer drugs. 1,3-Dibenzyl-2-aryl imidazolidine (8) is a previously reported inhibitor of HSP90; however, its anticancer activity is poor. In this work, chemical modification of 8 led to the discovery of 2,4-diarylimidazoles and 2,4-bis(benzyloxy)-5-arylpyrimidines as two types of novel HSP90 N-terminal inhibitors. 16l and 22k exhibited antiproliferative activity against multiple breast cancer cell lines with IC50 values at the low micromolar level. 16l and 22k induced significant degradation of the client proteins AKT and ERK and a lower level of the heat shock response in comparison with tanespimycin (17-AAG). 22k exhibited a strong affinity for the HSP90α N-terminus with an IC50 value of 0.21 µM. A molecular docking study revealed that 16l and 22k successfully bind to the geldanamycin binding site at the N-terminus of HSP90α.

A Retrospective Study of Double Eyelid Surgery for Sunken Upper Eyelid in Chinese.

OBJECTIVE: The aim of this study was to explore the effective technique of double eyelid surgery for mild, moderate, and severe sunken upper eyelid in Chinese. METHODS: According to the degree of the sunken upper eyelid, different procedures were performed. For mild sunken upper eyelid, the key technique was named eyelid volume redistribution (EVR)-1 technique, which was advancing or folding the pretarsal orbicularis oculi muscle flap toward up to the upper margin of the incision. For moderate sunken upper eyelid, the EVR-2 technique included EVR-1 technique and releasing orbital fat toward the upper margin of the tarsus. The other surgical steps were the same as conventional double eyelid surgery. For severe sunken upper eyelid, 2 steps were needed. The first step was eyelid volume augmentation (EVA). This technique injected fat into the retroorbicularis oculi fat layer. The second step was conventional double eyelid surgery which was performed 3 to 6 months later. RESULTS: One hundred sixty-seven patients with sunken upper eyelid underwent double eyelid surgery. In addition to the ameliorative recontouring of the sunken deformity, natural double eyelid was created. All patients had no complication, such as infection, skin irregularities, and lumps. The edema, bruising, and temporary ptosis recovered in 2 weeks. The edema resulted from double eyelid surgery, which last about 2 to 3 months. CONCLUSIONS: Our study showed that EVR-1, EVR-2, and EVA techniques have stable surgical results for mild, moderate, and severe sunken upper eyelids in Chinese. The procedures are simple, safe, and have less complications and preferable clinical reference value.

Effects of photoelectric therapy on proliferation and apoptosis of scar cells by regulating the expression of microRNA-206 and its related mechanisms.

Human skin fibroblast (HSF) cells were irradiated with different energy lasers to detect cell proliferation, apoptosis, and expression of microRNA-206 and protein, and to further summarise the therapeutic effect of laser on scar cells. Human scar cell line HSF cells were cultured in three groups. The control group was not irradiated by laser, the low-energy group was irradiated by 10 J/cm2 laser, and the high-energy group was irradiated by 20 J/cm2 laser. After irradiation, HSF cells were cultured for 20 hours. Cell proliferation was detected by MTT assay. Cell cycle and apoptosis were detected by flow cytometry. Transwell migration assay was used to detect cell migratory ability. Reverse transcription polymerase chain reaction (RT-PCR) was used to detect miR-206 and mTOR gene levels. The levels of MMP-9, Bax, Bcl-2, cyclin D1, and mTOR signalling pathway proteins were detected by Western blotting assays. The results showed that after laser irradiation, the proliferation of cells decreased, and the difference between the control group and the experimental group was significant (P < .05). The higher the energy was, the greater the upregulation of apoptosis was. Apoptosis and cell migration increased (P < .05). The expressions of microRNA-206, MMP-9, and Bax were upregulated, while the expressions of mTOR, Bcl-2, and cyclin D1 were downregulated. To sum up, laser irradiation can significantly inhibit the proliferation of HSF cells, affect cell cycle, and increase cell apoptosis and migratory ability.

Short Nose Correction: Septal Cartilage Combined With Ethmoid Bone Graft.

BACKGROUND: Multiple methods are employed to correct short nose deformities, with septal extension graft representing the first choice for Asians. However, the volume of the septal cartilage in many Asian patients is not sufficient to be used alone for such operation. The present work developed a new method combining the septal cartilage with ethmoid bone graft to overcome this issue in Asian patients with short noses. METHODS: Thirty-five women with short noses underwent septal extension graft from February 2015 to March 2017. The endoscopic technique was utilized to harvest the ethmoid bone to enhance the L-strut structure. An L-strut, comprising 0.8 cm segments of the caudal and dorsal cartilaginous septa, is left altered in order to harvest more cartilage for septal extension. The harvested the septal cartilage, approximately 1.0 mm thick and 16 to 20 mm long, underwent grafting on one side of the caudal septum. This was followed by alar cartilage fixation at the septal cartilage graft end. Finally, nose length, nasal tip projection and nasolabial angle were assessed before and after the surgery. RESULTS: Septal cartilage combined with ethmoid bone graft yielded an adequate nose lengthening and reduced nostril show, also in individuals showing extremely little septal cartilage. CONCLUSIONS: This new method is effective for short nose deformity correction in Asian patients. Combining the septal cartilage with ethmoid bone graft yields ideal outcome without overt complications, achieving commendable patient satisfaction.

A Novel Technique for Short Nose Correction in Asians: M-Shaped Conchal Cartilage Combining With Septal Extension Graft.

BACKGROUND: Multiple techniques are available for short nose deformity correction. The septal extension graft represents the commonest method employed in Asians. However, a large number of surgeons hardly obtain esthetically satisfactory results since the majority of designs do not reflect the normally encountered surface anatomy of the nasal tip cartilage. OBJECTIVE: The authors designed a novel technique, which combined the M-shaped conchal cartilage with the septal extension graft for overcoming the above shortcoming in Asians. METHODS: Between February 2013 and March 2016, 33 patients presenting short nose deformity were surgically treated with the M-shaped conchal cartilage combined with the septal extension graft. The graft was an altered septal extension graft using the septal cartilage alongside the conchal cartilage. The harvested septal cartilage was located to the caudal septum and fixed with sutures. The conchal cartilage was trimmed into 2 strips, which were sutured together in an M-shape and firmly fixed in a bilateral manner to the caudal septal extension graft. Then, the alar cartilage was fixed with the M-shape graft. In all patients, nasal lengths, nasal tip projections, and nasolabial angles were assessed before and after surgery, respectively. RESULTS: Nasal tip projections and nasal lengths showed remarkable increases, while columellar-labial angles were overtly decreased, in individuals surgically treated by the novel technique. CONCLUSIONS: This study presents a new method for correcting short nose deformity in Asians. The M-shaped conchal cartilage combined with the septal extension graft may effectively lengthen the nose while closely representing the actual surface of the esthetic nasal tip.

Anatomical Characteristics of the Perpendicular Plate of the Ethmoid: An Analysis of Paranasal Sinus Computed Tomography via Three-Dimensional Reconstruction.

In recent years, the perpendicular plate of the ethmoid (PPE) has emerged as a new autogenous grafting material in rhinoplasty and septoplasty of nasal deviation. However, no studies have outlined the precise size, shape, and morphologic features of the PPE. Therefore, this study aimed to provide detailed information on the anatomical and morphologic characteristics of the PPE to assist surgeons in performing surgeries that are more precise. About 104 Chinese patients who underwent paranasal computed tomography were assessed in this study. By analyzing the features of the PPE reconstructed with 3-dimensional models, the characteristics of the PPE at different stages of development and according to sex were observed. The PPE had a flat shape, and its lower part was relatively thin. It usually developed horizontally with age, which contributed to expansion of the PPE area. The dimensions of the PPE were significantly larger in male patients than in female patients. Through the reconstruction and measurement of Chinese patients' PPE, the authors have established precise information about the PPE's anatomical and morphologic features. The flat shape and proper size, which are similar to those of nasal septum cartilage, make the PPE an ideal alternative to conventional autogenous grafting materials. The findings might be useful to surgeons in helping them perform surgeries that are more precise.

Identification and Structure-Activity Studies of 1,3-Dibenzyl-2-aryl imidazolidines as Novel Hsp90 Inhibitors.

Hsp90 (Heat shock protein 90) is involved in various processes in cancer occurrence and development, and therefore represents a promising drug target for cancer therapy. In this work, a virtual screening strategy was employed, leading to the identification of a series of compounds bearing a scaffold of 1,3-dibenzyl-2-aryl imidazolidine as novel Hsp90 inhibitors. Compound 4a showed the highest binding affinity to Hsp90α (IC50 = 12 nM) in fluorescence polarization (FP) competition assay and the strongest anti-proliferative activity against human breast adenocarcinoma cell line (MCF-7) and human lung epithelial cell line (A549) with IC50 values of 21.58 µM and 31.22 µM, respectively. Western blotting assays revealed that these novel Hsp90 inhibitors significantly down-regulated the expression level of Her2, a client protein of Hsp90, resulting in the cytotoxicity of these novel Hsp90 inhibitors. The molecular docking study showed that these novel Hsp90 inhibitors bound to the adenosine triphosphate (ATP) binding site at the N-terminus of Hsp90. Furthermore, structure-activity relationship studies indicated that the N-benzyl group is important for the anti-cancer activity of 1,3-dibenzyl-2-aryl imidazolidines.

Metal-free C-H mercaptalization of benzothiazoles and benzoxazoles using 1,3-propanedithiol as thiol source.

A facile and effective C-H functionalization strategy for the synthesis of 2-mercaptobenzothiazoles and 2-mercaptobenzoxazoles is described. 1,3-Propanedithiol was employed to convert benzothiazoles and benzoxazoles to the corresponding heteroarylthiols in the presence of potassium hydroxide and DMSO. This novel protocol is featured by direct C-H mercaptalization of heteroarenes and a simple reaction system.

Adjustable V-Flap Epicanthoplasty Based on Desired Eyelid Morphology.

Eyelid shape is one key distinctive feature of the Asian eye. The presence of epicanthal folds is a common eyelid defect of Asians. Different surgical techniques have been developed to correct epicanthal folds. However, potential problems with these techniques are emerging, such as difficulty in design, recurrence and/or prominent scarring after surgery, and restricted application together with double eyelidplasty. An improved epicanthoplasty technique with high simplicity and flexibility is imperative. From October 2000 to March 2017, we performed V-flap epicanthoplasty procedures on 423 Asian patients. The whole procedure, including V-shaped skin incision, myotomy and pilication of the medial canthal ligament was performed layer by layer. A similar palpebral fissure distance and inner canthal distance were acquired with this surgical operation. Besides, this surgical technique will not cause limitations on double eyelid morphology when a double blepharoplasty is performed at the same period. The V-flap epicanthoplasty we described here is able to fully correct the epicanthal folds with a simple and flexible design, and the surgery can be adjusted according to patient needs for desired double eyelid shape. Satisfactory results were ideally achieved with no recurrence and finer scar.Level of evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to the table of contents or the online instructions to authors www.springer.com/00266 .

Upper Arch Flap Combined with Extended Incision of Lower Eyelid: A Modified Epicanthoplasty in Correcting Epicanthus.

BACKGROUND: The epicanthus, a lengthways cambered skinfold around the inner canthus, is particularly common in Orientals. The purpose of this study was to evaluate the surgical outcomes for patients with epicanthus after the application of a new surgical technique. METHODS: A total of 753 patients with epicanthus underwent epicanthoplasty in our hospital from October 2009 to March 2017 and were enrolled in this study. All patients were treated with upper arch flap combined with extended incision of the lower eyelid surgical method, and the effects of the surgery were assessed by photographic analysis and satisfaction surveys. RESULTS: After the surgery, the eyelids of patients were elongated, and their inner canthi diameter was shortened without recurrence in the epicanthus. For 3.32% of the patients, there was a nonuniform edge thickness of the lower eyelid incision; for 8.23% of the patients, there was a slightly lighter skin color in the rest of quondam arch flap. Six months after the surgery, the incision scar was not obvious for all patients, and most of the patients (90.31%) were satisfied with the effect of the surgery. CONCLUSIONS: The upper arch flap combined with extended incision of the lower eyelid surgical method, a simple and effective surgical correction method, obtained a good cosmetic result with more secluded scar and high satisfaction for patients with epiblepharon. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

[Hippocampal neuron damage and cognitive dysfunction of diabetic Wistar rats].

This study aimed to explore the cognitive dysfunction of and hippocampal neuron damage to Wistar rats with STZ-induced diabetes at different morbidity time. All Wistar rats in the tests received intraperitoneal injections of streptozotocin (STZ; 60 mg/kg) to induce type 1 diabetes. The concentration of blood glucose and the body weight were investigated, the cognitive ability of rats was assessed using a standardized Y-maze, and the apoptotic neurons in the CA1 of the hippocampus were also examined by using the HE staining. While the sickening time was prolonged, the blood glucose concentration of the experimental rats increased continuously and the body weight decreased. On the 70th day after STZ administration, the neuronal loss in the hippocampal CA1 region increased and the working errors increased in rats with the diabetes. The results showed that Wistar rats could complicate with diabetic encephalopathy in 70 days after injection of STZ for inducing the diabetes.

Restoring long-lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study.

BACKGROUND: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface. METHODS: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1-point improvement from baseline on both sides of the face. RESULTS: HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL. Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. CONCLUSIONS: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.